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Nagao T, Yokoyama Y, Abe T, Miyata K, Sugita S, Ogura A, Murata Y, Higaki E, Fujieda H, Asahara T, Shimizu Y, Ebata T. The Ratio of the Preoperative Fecal Short-Chain Fatty Acid to Lactic Acid Concentrations as a Predictor of Postoperative Infectious Complications After Esophagectomy. Ann Surg Oncol 2025:10.1245/s10434-025-17347-0. [PMID: 40314905 DOI: 10.1245/s10434-025-17347-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Accepted: 04/04/2025] [Indexed: 05/03/2025]
Abstract
BACKGROUND The ratio of the fecal short-chain fatty acid (SCFA) to lactic acid concentrations (APB-L ratio) is a useful indicator for the healthiness of the intestinal microenvironment. A recent study indicated that the low APB-L ratio can be a predictor of postoperative infectious complications (POICs) in patients undergoing pancreaticoduodenectomy. However, the predictive power of the APB-L ratio in other highly invasive surgeries, such as esophagectomy, is still unclear. This study investigated whether the APB-L ratio can be a sensitive predictor of POICs in patients undergoing esohpagectomy. METHODS A total of 129 patients undergoing esohpagectomy with gastric conduit reconstruction were included in this study. Preoperative fecal samples were analyzed for SCFA and lactic acid concentrations. The associations between clinical characteristics, POICs, and the APB-L ratio were analyzed. Preoperative and intraoperative risk factors for POICs were explored via multivariate logistic regression analysis. RESULTS Postoperative infectious complications were observed in 34 patients (26%), including surgical site infections in 18 patients (14%). A low APB-L ratio was significantly associated with higher POICs and surgical site infections risk (both p < 0.05). A low APB-L ratio was identified as an independent risk factor for POICs, with an odds ratio of 3.62 (95% confidence interval, 1.44-9.10, p = 0.006). CONCLUSIONS The APB-L ratio measured with preoperative fecal organic acid concentrations is useful to assess the risk of POICs for esohpagectomy. The results also imply the importance of maintaining a healthy intestinal metabolism (thus high APB-L ratio) to reduce POICs before highly invasive surgery.
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Affiliation(s)
- Takuya Nagao
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yukihiro Yokoyama
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
- Department of Surgery, Division of Perioperative Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| | - Tetsuya Abe
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kazushi Miyata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shizuki Sugita
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Atsushi Ogura
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuki Murata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Eiji Higaki
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Hironori Fujieda
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Takashi Asahara
- Yakult Central Institute, Yakult Honsho Co., Ltd., Tokyo, Japan
| | - Yasuhiro Shimizu
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
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Sujaya IN, Mariyatun M, Hasan PN, Manurung NEP, Pramesi PC, Juffrie M, Utami T, Cahyanto MN, Yamamoto S, Takahashi T, Asahara T, Akiyama T, Rahayu ES. Randomized study of Lacticaseibacillus fermented milk in Indonesian elderly houses: Impact on gut microbiota and gut environment. World J Gastroenterol 2025; 31:104081. [PMID: 40182598 PMCID: PMC11962840 DOI: 10.3748/wjg.v31.i12.104081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/21/2025] [Accepted: 02/24/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Health maintenance in elderly houses includes management of the gut microbiota and the environment. Lacticaseibacillus paracasei Shirota (LcS) is a probiotic strain that positively affects the human gut. However, the evidence of its effects on the Indonesian population remains limited. AIM To investigate the effect of LcS-fermented milk on the gut microbiota and environment of Indonesian elderly houses. METHODS This double-blind, randomized, placebo-controlled trial involved 112 participants from Indonesian elderly houses, spanning a 2-week baseline and 24-week treatment. Participants were randomly assigned to probiotic or placebo groups, consuming fermented milk with or without LcS (> 6.5 × 109 colony-forming units). Fecal samples were collected every three months. Gut microbiota analysis was performed using 16S rRNA gene sequencing and reverse transcription quantitative polymerase chain reaction, while gut environment was assessed by measuring fecal organic acids, amino acid metabolites, and stool frequency. RESULTS Analyses of 16S rRNA gene sequence data at the 3-month period revealed increased Bifidobacterium and Succinivibrio and decreased Rikenellaceae RC9 gut group in the probiotic group. These shifts were associated with significant differences in β-diversity metrics. The change in Bifidobacterium was confirmed by reverse transcription quantitative polymerase chain reaction, demonstrating higher abundance in the probiotic group than in the placebo group (8.5 ± 1.1 vs 8.0 ± 1.1, log10 bacterial cells/g; P = 0.044). At 6-month period, the differences in Succinivibrio and Rikenellaceae RC9 gut group persisted. The probiotic group showed higher butyrate levels than the placebo group at the 6-month period (5.04 ± 3.11 vs 3.95 ± 2.89, μmol/g; P = 0.048). The effect on amino acid metabolites and stool frequency was not significant. CONCLUSION Daily intake of LcS positively affects the gut microbiota and environment of people living in Indonesian elderly houses.
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Affiliation(s)
- I Nengah Sujaya
- School of Public Health, Faculty of Medicine, Udayana University, Denpasar 80230, Bali, Indonesia
| | - Mariyatun Mariyatun
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Pratama Nur Hasan
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Nancy Eka Putri Manurung
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Putrika Citta Pramesi
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Mohammad Juffrie
- Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Tyas Utami
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Muhammad Nur Cahyanto
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
| | - Shuta Yamamoto
- Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi 186-8650, Tōkyō, Japan
| | - Takuya Takahashi
- Yakult Honsha European Research Center for Microbiology VOF, Ghent 9052, East Flanders, Belgium
| | - Takashi Asahara
- Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi 186-8650, Tōkyō, Japan
| | - Takuya Akiyama
- Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi 186-8650, Tōkyō, Japan
| | - Endang Sutriswati Rahayu
- Center for Food and Nutrition Studies, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Center of Excellence for Research and Application on Integrated Probiotics Industry, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
- Department of Food and Agricultural Product Technology, Faculty of Agricultural Technology, Universitas Gadjah Mada, Sleman 55281, Daerah Istimewa Yogyakarta, Indonesia
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Korsten SGPJ, Hartog M, Berends AJ, Koenders MI, Popa CD, Vromans H, Garssen J, van de Ende CHM, Vermeiden JPW, Willemsen LEM. A Sustained-Release Butyrate Tablet Suppresses Ex Vivo T Helper Cell Activation of Osteoarthritis Patients in a Double-Blind Placebo-Controlled Randomized Trial. Nutrients 2024; 16:3384. [PMID: 39408351 PMCID: PMC11478393 DOI: 10.3390/nu16193384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 09/25/2024] [Accepted: 10/01/2024] [Indexed: 10/20/2024] Open
Abstract
Degenerative joint disease osteoarthritis (OA) is characterized by the degeneration of cartilage, synovial inflammation and low-grade systemic inflammation in association with microbial dysbiosis and intestinal barrier defects. Butyrate is known for its anti-inflammatory and barrier protective effects and might benefit OA patients. In a double-blind placebo-controlled randomized trial, the effects of four to five weeks of oral treatment with sustained-release (SR) butyrate tablets (600 mg/day) on systemic inflammation and immune function were studied in hand OA patients. Serum markers for systemic inflammation and lipopolysaccharide (LPS) leakage were measured and ex vivo stimulation of whole blood or peripheral blood mononuclear cells (PBMCs) was performed at baseline and after treatment. Butyrate treatment did not affect the serum markers nor the cytokine release of ex vivo LPS-stimulated whole blood or PBMCs nor the phenotype of restimulated monocytes. By contrast, butyrate treatment reduced the percentage of activated T helper (Th) cells and the Th17/Treg ratio in αCD3/CD28-activated PBMCs, though cytokine release upon stimulation remained unaffected. Nevertheless, the percentage of CD4+IL9+ cells was reduced by butyrate as compared to the placebo. In both groups, the frequency of Th1, Treg, Th17, activated Th17, CD4+IFNγ+ and CD4+TNFα+ cells was reduced. This study shows a proof of principle of some immunomodulatory effects using a SR butyrate treatment in hand OA patients. The inflammatory phenotype of Th cells was reduced, as indicated by a reduced percentage of Th9 cells, activated Th cells and improved Th17/Treg balance in ex vivo αCD3/CD28-activated PBMCs. Future studies are warranted to further optimize the butyrate dose regime to ameliorate inflammation in OA patients.
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Affiliation(s)
- Sandra G. P. J. Korsten
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands (J.G.)
- Tiofarma B.V., 3261 ME Oud-Beijerland, The Netherlands
| | - Merel Hartog
- Department of Research, Sint Maartenskliniek, 6574 NA Ubbergen, The Netherlands; (M.H.); (C.H.M.v.d.E.)
- Department of Rheumatology, Sint Maartenskliniek, 6574 NA Ubbergen, The Netherlands;
| | - Alinda J. Berends
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands (J.G.)
| | - Marije I. Koenders
- Department of Rheumatology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Calin D. Popa
- Department of Rheumatology, Sint Maartenskliniek, 6574 NA Ubbergen, The Netherlands;
- Department of Rheumatology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
| | - Herman Vromans
- Tiofarma B.V., 3261 ME Oud-Beijerland, The Netherlands
- Division of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands (J.G.)
- Danone/Nutricia Research B.V., 3584 CT Utrecht, The Netherlands
| | - Cornelia H. M. van de Ende
- Department of Research, Sint Maartenskliniek, 6574 NA Ubbergen, The Netherlands; (M.H.); (C.H.M.v.d.E.)
- Department of Rheumatology, Sint Maartenskliniek, 6574 NA Ubbergen, The Netherlands;
| | | | - Linette E. M. Willemsen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands (J.G.)
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González A, Fullaondo A, Odriozola I, Odriozola A. Microbiota and beneficial metabolites in colorectal cancer. ADVANCES IN GENETICS 2024; 112:367-409. [PMID: 39396841 DOI: 10.1016/bs.adgen.2024.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. In recent years, the impact of the gut microbiota on the development of CRC has become clear. The gut microbiota is the community of microorganisms living in the gut symbiotic relationship with the host. These microorganisms contribute to the development of CRC through various mechanisms that are not yet fully understood. Increasing scientific evidence suggests that metabolites produced by the gut microbiota may influence CRC development by exerting protective and deleterious effects. This article reviews the metabolites produced by the gut microbiota, which are derived from the intake of complex carbohydrates, proteins, dairy products, and phytochemicals from plant foods and are associated with a reduced risk of CRC. These metabolites include short-chain fatty acids (SCFAs), indole and its derivatives, conjugated linoleic acid (CLA) and polyphenols. Each metabolite, its association with CRC risk, the possible mechanisms by which they exert anti-tumour functions and their relationship with the gut microbiota are described. In addition, other gut microbiota-derived metabolites that are gaining importance for their role as CRC suppressors are included.
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Affiliation(s)
- Adriana González
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Asier Fullaondo
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Iñaki Odriozola
- Health Department of Basque Government, Donostia-San Sebastián, Spain
| | - Adrian Odriozola
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain.
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Adamberg S, Adamberg K. Prevotella enterotype associates with diets supporting acidic faecal pH and production of propionic acid by microbiota. Heliyon 2024; 10:e31134. [PMID: 38779015 PMCID: PMC11109898 DOI: 10.1016/j.heliyon.2024.e31134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 03/21/2024] [Accepted: 05/10/2024] [Indexed: 05/25/2024] Open
Abstract
Metabolism of dietary fibres by colon microbiota plays an important role for human health. Personal data from a nutrition study (57 subjects) were analysed to elucidate quantitative associations between the diet, faecal microbiome, organic acid concentrations and pH. Ratios of the predominant acids acetate, butyrate and propionate ranged from 1:0.67:0.27 to 1:0.17:0.36. Pectin-rich diets resulted in higher faecal acetate concentrations. Negative correlation between faecal pH and BSS was observed. Higher faecal pH and lower acid concentrations were related to the higher abundance of amino acid degrading Clostridium, Odoribacter and Eubacterium coprostanoligenes, which are weak carbohydrate fermenting taxa. Propionic acid correlated especially to high abundance of Prevotella and low abundance of proteobacteria. The acetate to propionate ratio of the Prevotella enterotype was about half of that of the Bacteroides enterotype. Based on the results we suggest the measurement of faecal pH and organic acid composition for research and diagnostic purposes.
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Affiliation(s)
- Signe Adamberg
- Tallinn University of Technology, Department of Chemistry and Biotechnology, 12618, Tallinn, Estonia
| | - Kaarel Adamberg
- Tallinn University of Technology, Department of Chemistry and Biotechnology, 12618, Tallinn, Estonia
- Center of Food and Fermentation Technologies, 12618, Tallinn, Estonia
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Kaźmierczak-Siedlecka K, Muszyński D, Styburski D, Makarewicz J, Sobocki BK, Ulasiński P, Połom K, Stachowska E, Skonieczna-Żydecka K, Kalinowski L. Untargeted metabolomics in gastric and colorectal cancer patients - preliminary results. Front Cell Infect Microbiol 2024; 14:1394038. [PMID: 38774628 PMCID: PMC11106370 DOI: 10.3389/fcimb.2024.1394038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 04/08/2024] [Indexed: 05/24/2024] Open
Abstract
Introduction Recent years, microbiota-associated aspects have been analysed in multiple disorders regarding cancers. Existing evidence pints that gut microorganisms might take part in tumour origin and therapy efficacy. Nevertheless, to date, data on faecal metabolomics in cancer patients is still strongly limited. Therefore, we aimed to analyse gut untargeted metabolome in gastrointestinal cancer patients (i.e., gastric and colorectal cancer). Patients and methods There were 12 patients with either gastric (n=4) or colorectal cancer (n=8) enrolled and 8 analysed (n=4 each). Stool samples were collected prior to anti-cancer treatments. Untargeted metabolomics analyses were conducted by means of mass spectrometry. Results A plethora of metabolites in cancer patients we analysed were noted, with higher homogenity in case of gastric cancer patients. We found that the level of Deoxyguanosine,m/z 266.091,[M-H]-, Uridine,m/z 245.075,[M+H]+, Deoxyguanosine,m/z 268.104,[M]+, 3-Indoleacetic acid,m/z 176.07,[M+H]+, Indoxyl,m/z 132.031,[M-H]-, L-Phenylalanine,m/z 164.073,[M-H]-, L-Methionine,m/z 150.058,[M+NH4]+, was significantly higher in colorectal cancer patients and Ethyl hydrogen malonate,m/z 133.031,[M+H]+ in gastric cancer. Conclusion The overall insights into untargeted metabolomics showed that most often higher levels of analysed metabolites were detected in colorectal cancer patients compared to gastric cancer patients. The link between gut metabolome and both local and distal metastasis might exist, however it requires confirmation in further multi-centre studies regarding larger sample size.
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Affiliation(s)
- Karolina Kaźmierczak-Siedlecka
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdansk, Poland
| | - Damian Muszyński
- Scientific Circle of Studies Regarding Personalized Medicine Associated with Department of Medical Laboratory Diagnostics, Medical University of Gdansk, Gdansk, Poland
| | | | - Jakub Makarewicz
- Scientific Circle of Studies Regarding Personalized Medicine Associated with Department of Medical Laboratory Diagnostics, Medical University of Gdansk, Gdansk, Poland
| | - Bartosz Kamil Sobocki
- Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland
| | - Paweł Ulasiński
- Unit of Surgery with Unit of Surgery with Unit of Oncological Surgery, Specialist Hospital in Koscierzyna, Koscierzyna, Poland
| | - Karol Połom
- Academy of Medical and Social Applied Sciences, Elbląg, Poland
- Department of Surgical Oncology, Medical University of Gdansk, Gdansk, Poland
- Department of Gastrointestinal Surgical Oncology, Greater Poland Cancer Centre, Poznan, Poland
| | - Ewa Stachowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | | | - Leszek Kalinowski
- Department of Medical Laboratory Diagnostics – Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Gdansk, Poland
- BioTechMed Centre/Department of Mechanics of Materials and Structures, Gdansk University of Technology, Gdansk, Poland
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Fan L, Zhu X, Chen Q, Huang X, Steinwandel MD, Shrubsole MJ, Dai Q. Dietary medium-chain fatty acids and risk of incident colorectal cancer in a predominantly low-income population: a report from the Southern Community Cohort Study. Am J Clin Nutr 2024; 119:7-17. [PMID: 37898435 PMCID: PMC10808834 DOI: 10.1016/j.ajcnut.2023.10.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 10/05/2023] [Accepted: 10/24/2023] [Indexed: 10/30/2023] Open
Abstract
BACKGROUND No prospective observational study has specifically examined the associations between dietary intakes of medium-chain fatty acids and risk of colorectal cancer. OBJECTIVES This study examined the association between dietary intakes of medium-chain fatty acids and colorectal cancer risk overall and by racial subgroups in a predominantly low-income United States population. METHODS This prospective study included 71,599 eligible participants aged 40 to 79 who were enrolled in the Southern Community Cohort Study between 2002 and 2009 in 12 southeastern United States states. Incident colorectal cancer cases were ascertained via linkage to state cancer registries, which was completed through 31 December, 2016. The dietary intakes of medium-chain fatty acids were assessed using a validated 89-item food frequency questionnaire. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between intakes of medium-chain fatty acids and risk for incident colorectal cancer. RESULTS Among 71,599 participants, 48,008 (67.3%) were Black individuals and 42,260 (59.0%) were female. A total of 868 incident colorectal cancer cases occurred during a median follow-up of 13.7 y. Comparing the highest to the lowest quartile, high intake of dodecanoic acid/lauric acid (C12:0) was associated with reduced risk of colorectal cancer among White participants (HR: 0.52; 95% CI: 0.30, 0.91; P-trend = 0.05), but not in Black individuals (HR: 0.92; 95% CI, 0.68, 1.24; P-trend = 0.80) in multivariable-adjusted models. No associations were found between intakes of hexanoic acid/caproic acid (C6:0), octanoic acid/caprylic acid (C8:0), or decanoic acid/capric acid (C10:0) and risk of incident colorectal cancer overall or within racial subgroups. CONCLUSIONS In a predominantly low-income United States population, an increased dietary C12:0 intake was associated with a substantially reduced risk of colorectal cancer only among White individuals, but not in Black individuals.
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Affiliation(s)
- Lei Fan
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Xiangzhu Zhu
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Qingxia Chen
- Department of Biostatistics, Vanderbilt University, Nashville, TN, United States
| | - Xiang Huang
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | | | - Martha J Shrubsole
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Qi Dai
- Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States.
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Kashihara H, Okikawa S, Morine Y, Yoshikawa K, Tokunaga T, Nishi M, Takasu C, Nishiyama M, Zushi M, Shimada M. Impact of Daikenchuto (TU-100) on the early postoperative period in duodenal-jejunal bypass. THE JOURNAL OF MEDICAL INVESTIGATION 2024; 71:210-218. [PMID: 39462554 DOI: 10.2152/jmi.71.210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/29/2024]
Abstract
INTRODUCTION We investigated the effect of Daikenchuto (TU-100) on the early postoperative period in duodenal-jejunal bypass (DJB). METHODS Study 1:The effect of TU-100 on diabetic rats was investigated. Rats were sacrificed after receiving TU-100 for one week. Study 2:The effect of TU-100 on DJB was investigated. Rats in the DJB and TU-100 treated DJB groups were sacrificed 24 hours postoperation to evaluate blood glucose, cytokine expression, and gut microbiome. RESULTS Study 1:TU-100 did not affect glucose or body weight. TU-100 suppressed intestinal inflammation and modified the gut microbiome. Specifically, Bifidobacterium and Blautia were increased, and Turicibacter were decreased in this group. Study 2:Both DJB and TU-100 treated DJB rats showed lower blood glucose at 24 hours postoperation than at preoperation. Cytokine expression in the liver and small intestine of the TU-100 treated DJB group was significantly lower than that of the DJB group. The gut microbiome composition in TU-100 treated DJB rats was altered. In particular, Bifidobacterium and Blautia were increased in this group. CONCLUSION DJB suppressed blood glucose during the early postoperative period. TU-100 may enhance the anti-diabetic effect of metabolic surgery by changing the gut microbiome and suppressing inflammation in the early postoperative period. J. Med. Invest. 71 : 210-218, August, 2024.
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Affiliation(s)
| | - Shohei Okikawa
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Yuji Morine
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Kozo Yoshikawa
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Takuya Tokunaga
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Masaaki Nishi
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Chie Takasu
- Department of Surgery, Tokushima University, Tokushima, Japan
| | - Mitsue Nishiyama
- Tsumura Kampo Research Laboratories, Tsumura & Co., Ami, Ibaraki, Japan
| | - Makoto Zushi
- Tsumura Kampo Research Laboratories, Tsumura & Co., Ami, Ibaraki, Japan
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima, Japan
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Morisaki Y, Miyata N, Nakashima M, Hata T, Takakura S, Yoshihara K, Suematsu T, Nomoto K, Miyazaki K, Tsuji H, Sudo N. Persistence of gut dysbiosis in individuals with anorexia nervosa. PLoS One 2023; 18:e0296037. [PMID: 38117788 PMCID: PMC10732397 DOI: 10.1371/journal.pone.0296037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 12/03/2023] [Indexed: 12/22/2023] Open
Abstract
Recent evidence suggests a crucial role of the gut microbiota in the pathogenesis of anorexia nervosa (AN). In this study, we carried out a series of multiple analyses of the gut microbiota of hospitalized individuals with AN over three months using 16S or 23S rRNA-targeted reverse transcription-quantitative polymerase chain reaction (PCR) technology (YIF-SCAN®), which is highly sensitive and enables the precise quantification of viable microorganisms. Despite the weight gain and improvements in psychological features observed during treatment, individuals with AN exhibited persistent gut microbial dysbiosis over the three-month duration. Principal component analysis further underscored the distinct microbial profile of individuals with AN, compared with that of age-matched healthy women at all time points. Regarding the kinetics of bacterial detection, the detection rate of Lactiplantibacillus spp. significantly increased after inpatient treatment. Additionally, the elevation in the Bifidobacterium counts during inpatient treatment was significantly correlated with the subsequent body weight gain after one year. Collectively, these findings suggest that gut dysbiosis in individuals with AN may not be easily restored solely through weight gain, highlighting the potential of therapeutic interventions targeting microbiota via dietary modifications or live biotherapeutics.
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Affiliation(s)
- Yukiko Morisaki
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Noriyuki Miyata
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Megumi Nakashima
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Tomokazu Hata
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shu Takakura
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Kazufumi Yoshihara
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- Center for Health Sciences and Counseling, Kyushu University, Fukuoka, Japan
| | - Takafumi Suematsu
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Koji Nomoto
- Faculty of Life Sciences, Department of Molecular Microbiology, Tokyo University of Agriculture, Setagaya City, Japan
| | | | | | - Nobuyuki Sudo
- Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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10
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Bahuguna A, Dubey SK. Overview of the Mechanistic Potential of Probiotics and Prebiotics in Cancer Chemoprevention. Mol Nutr Food Res 2023; 67:e2300221. [PMID: 37552810 DOI: 10.1002/mnfr.202300221] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/15/2023] [Indexed: 08/10/2023]
Abstract
Despite of strides in modern cancer therapeutic strategies, there has not been a successful cure for it until now and prognostic side effects and substantial toxicity to chemotherapy and subsequent homeostatic imbalance remains a major concern for professionals in this field. The significance of the human microbiome in the pathogenesis of cancer is being recognized, documented, and established worldwide. Probiotics and prebiotics are some of the most extensively researched approaches to modulate the microbiota for therapeutic purposes, and research on their potential to prevent and treat cancer has sparked an immense amount of interest. The characteristics of probiotics and prebiotics allow for an array of efficient applications in cancer preventive measures. Probiotics can also be administered coupled with chemotherapy and surgery to alleviate their side effects and help promote the effectiveness of chemotherapeutic drugs. Besides showing promising results they are accompanied by potential risks and controversies that may eventually result in clinical repercussions. This review emphasizes the mechanistic potential and oncosuppressive effects of probiotic and prebiotics through maintenance of intestinal barrier function, modifying innate immune system, immunomodulation, intestinal microbiota metabolism, inhibition of host cell proliferation, preventing pathogen colonization, and exerting selective cytotoxicity against tumor cells.
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Affiliation(s)
- Ananya Bahuguna
- Department of Biochemistry, C.B.S.H., G. B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand, 263145, India
| | - Shiv Kumar Dubey
- Department of Biochemistry, C.B.S.H., G. B. Pant University of Agriculture and Technology, Pantnagar, Uttarakhand, 263145, India
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11
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Wang D, Wang W, Wang P, Wang C, Niu J, Liu Y, Chen Y. Research progress of colon-targeted oral hydrogel system based on natural polysaccharides. Int J Pharm 2023; 643:123222. [PMID: 37454829 DOI: 10.1016/j.ijpharm.2023.123222] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 06/20/2023] [Accepted: 07/08/2023] [Indexed: 07/18/2023]
Abstract
The quality of life is significantly impacted by colon-related diseases. There have been a lot of interest in the oral colon-specific drug delivery system (OCDDS) as a potential carrier to decrease systemic side effects and protect drugs from degradation in the upper gastrointestinal tract (GIT). Hydrogels are effective oral colon-targeted drug delivery carriers due to their high biodegradability, substantial drug loading, and great biocompatibility. Natural polysaccharides give the hydrogel system unique structure and function to effectively respond to the complex environment of the GIT and deliver drugs to the colon. In this paper, the physiological factors of colonic drug delivery and the pathological characteristics of common colonic diseases are summarized, and the latest advances in the design, preparation and characterization of natural polysaccharide hydrogels are reviewed, which are expected to provide new references for colon-targeted oral hydrogel systems using natural polysaccharides as raw materials.
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Affiliation(s)
- Dingding Wang
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Weibo Wang
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Ping Wang
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Chuang Wang
- Shenyang Pharmaceutical University, Shenyang, China
| | - Juntao Niu
- Department of Otorhinolaryngology, Head and Neck Surgery, the Second Hospital, Tianjin Medical University, Tianjin, China
| | - Yang Liu
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
| | - Yuzhou Chen
- Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
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12
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Alhhazmi AA, Alhamawi RM, Almisned RM, Almutairi HA, Jan AA, Kurdi SM, Almutawif YA, Mohammed-Saeid W. Gut Microbial and Associated Metabolite Markers for Colorectal Cancer Diagnosis. Microorganisms 2023; 11:2037. [PMID: 37630597 PMCID: PMC10457972 DOI: 10.3390/microorganisms11082037] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 07/29/2023] [Accepted: 07/30/2023] [Indexed: 08/27/2023] Open
Abstract
Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community and its metabolite secretions play a fundamental role in advanced adenoma (ADA) and CRC development and progression. This study is a systematic review that aims to assess the clinical association between gut microbial markers and/or gut and circulating metabolites with ADA and CRC. Five electronic databases were searched by four independent reviewers. Only controlled trials that compared ADA and/or CRC with healthy control (HC) using either untargeted (16s rRNA gene or whole genome sequencing) or targeted (gene-based real-time PCR) identification methods for gut microbiome profile, or untargeted or targeted metabolite profiling approaches from the gut or serum/plasma, were eligible. Three independent reviewers evaluated the quality of the studies using the Cochrane Handbook for Systematic Reviews of Interventions. Twenty-four studies were eligible. We identified strong evidence of two microbial markers Fusobacterium and Porphyromonas for ADA vs. CRC, and nine microbial markers Lachnospiraceae-Lachnoclostridium, Ruminococcaceae-Ruminococcus, Parvimonas spp., Parvimonas micra, Enterobacteriaceae, Fusobacterium spp., Bacteroides, Peptostreptococcus-Peptostreptococcus stomatis, Clostridia spp.-Clostridium hylemonae, Clostridium symbiosum, and Porphyromonas-Porphyromonas asaccharolytica for CRC vs. HC. The remaining metabolite marker evidence between the various groups, including ADA vs. HC, ADA vs. HC, and CRC vs. HC, was not of sufficient quality to support additional findings. The identified gut microbial markers can be used in a panel for diagnosing ADA and/or CRC. Further research in the metabolite markers area is needed to evaluate the possibility to use in diagnostic or prognostic markers for colorectal cancer.
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Affiliation(s)
- Areej A. Alhhazmi
- Medical Laboratories Technology Department, College of Applied Medical Sciences, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 42353, Saudi Arabia; (R.M.A.); (S.M.K.); (Y.A.A.)
| | - Renad M. Alhamawi
- Medical Laboratories Technology Department, College of Applied Medical Sciences, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 42353, Saudi Arabia; (R.M.A.); (S.M.K.); (Y.A.A.)
| | - Reema M. Almisned
- Seha Polyclinic, P.O. Box 150, Al-Madinah Al-Munawarah 41311, Saudi Arabia;
| | - Hanouf A. Almutairi
- Bioscience Program, Biological and Environmental Science and Engineering Division, King Abdullah University of Science and Technology (KAUST), P.O. Box 6900, Thuwal 23955, Saudi Arabia;
| | - Ahdab A. Jan
- Abdulla Fouad Medical Supplies and Services (AFMS), P.O. Box 150, Al-Madinah Al-Munawarah 21414, Saudi Arabia;
| | - Shahad M. Kurdi
- Medical Laboratories Technology Department, College of Applied Medical Sciences, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 42353, Saudi Arabia; (R.M.A.); (S.M.K.); (Y.A.A.)
| | - Yahya A. Almutawif
- Medical Laboratories Technology Department, College of Applied Medical Sciences, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 42353, Saudi Arabia; (R.M.A.); (S.M.K.); (Y.A.A.)
| | - Waleed Mohammed-Saeid
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, P.O. Box 344, Al-Madinah Al-Munawarah 42353, Saudi Arabia;
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13
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Korsten SGPJ, Vromans H, Garssen J, Willemsen LEM. Butyrate Protects Barrier Integrity and Suppresses Immune Activation in a Caco-2/PBMC Co-Culture Model While HDAC Inhibition Mimics Butyrate in Restoring Cytokine-Induced Barrier Disruption. Nutrients 2023; 15:2760. [PMID: 37375664 DOI: 10.3390/nu15122760] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 06/12/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Low-grade inflammation and barrier disruption are increasingly acknowledged for their association with non-communicable diseases (NCDs). Short chain fatty acids (SCFAs), especially butyrate, could be a potential treatment because of their combined anti-inflammatory and barrier- protective capacities, but more insight into their mechanism of action is needed. In the present study, non-activated, lipopolysaccharide-activated and αCD3/CD28-activated peripheral blood mononuclear cells (PBMCs) with and without intestinal epithelial cells (IEC) Caco-2 were used to study the effect of butyrate on barrier function, cytokine release and immune cell phenotype. A Caco-2 model was used to compare the capacities of butyrate, propionate and acetate and study their mechanism of action, while investigating the contribution of lipoxygenase (LOX), cyclooxygenase (COX) and histone deacetylase (HDAC) inhibition. Butyrate protected against inflammatory-induced barrier disruption while modulating inflammatory cytokine release by activated PBMCs (interleukin-1 beta↑, tumor necrosis factor alpha↓, interleukin-17a↓, interferon gamma↓, interleukin-10↓) and immune cell phenotype (regulatory T-cells↓, T helper 17 cells↓, T helper 1 cells↓) in the PBMC/Caco-2 co-culture model. Similar suppression of immune activation was shown in absence of IEC. Butyrate, propionate and acetate reduced inflammatory cytokine-induced IEC activation and, in particular, butyrate was capable of fully protecting against cytokine-induced epithelial permeability for a prolonged period. Different HDAC inhibitors could mimic this barrier-protective effect, showing HDAC might be involved in the mechanism of action of butyrate, whereas LOX and COX did not show involvement. These results show the importance of sufficient butyrate levels to maintain intestinal homeostasis.
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Affiliation(s)
- Sandra G P J Korsten
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands
- Tiofarma B.V., 3261 ME Oud-Beijerland, The Netherlands
| | - Herman Vromans
- Tiofarma B.V., 3261 ME Oud-Beijerland, The Netherlands
- Division of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands
- Danone/Nutricia Research B.V., 3584 CT Utrecht, The Netherlands
| | - Linette E M Willemsen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands
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14
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Valciukiene J, Strupas K, Poskus T. Tissue vs. Fecal-Derived Bacterial Dysbiosis in Precancerous Colorectal Lesions: A Systematic Review. Cancers (Basel) 2023; 15:1602. [PMID: 36900392 PMCID: PMC10000868 DOI: 10.3390/cancers15051602] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 02/19/2023] [Accepted: 03/02/2023] [Indexed: 03/08/2023] Open
Abstract
Alterations in gut microbiota play a pivotal role in the adenoma-carcinoma sequence. However, there is still a notable lack of the correct implementation of tissue and fecal sampling in the setting of human gut microbiota examination. This study aimed to review the literature and to consolidate the current evidence on the use of mucosa and a stool-based matrix investigating human gut microbiota changes in precancerous colorectal lesions. A systematic review of papers from 2012 until November 2022 published on the PubMed and Web of Science databases was conducted. The majority of the included studies have significantly associated gut microbial dysbiosis with premalignant polyps in the colorectum. Although methodological differences hampered the precise fecal and tissue-derived dysbiosis comparison, the analysis revealed several common characteristics in stool-based and fecal-derived gut microbiota structures in patients with colorectal polyps: simple or advanced adenomas, serrated lesions, and carcinomas in situ. The mucosal samples considered were more relevant for the evaluation of microbiota's pathophysiological involvement in CR carcinogenesis, while non-invasive stool sampling could be beneficial for early CRC detection strategies in the future. Further studies are required to identify and validate mucosa-associated and luminal colorectal microbial patterns and their role in CRC carcinogenesis, as well as in the clinical setting of human microbiota studies.
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Affiliation(s)
- Jurate Valciukiene
- Clinic of Gastroenterology, Nephro-Urology, and Surgery, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania
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15
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Keane JM, Walsh CJ, Cronin P, Baker K, Melgar S, Cotter PD, Joyce SA, Gahan CGM, Houston A, Hyland NP. Investigation of the gut microbiome, bile acid composition and host immunoinflammatory response in a model of azoxymethane-induced colon cancer at discrete timepoints. Br J Cancer 2023; 128:528-536. [PMID: 36418894 PMCID: PMC9938136 DOI: 10.1038/s41416-022-02062-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 11/03/2022] [Accepted: 11/08/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Distinct sets of microbes contribute to colorectal cancer (CRC) initiation and progression. Some occur due to the evolving intestinal environment but may not contribute to disease. In contrast, others may play an important role at particular times during the tumorigenic process. Here, we describe changes in the microbiota and host over the course of azoxymethane (AOM)-induced tumorigenesis. METHODS Mice were administered AOM or PBS and were euthanised 8, 12, 24 and 48 weeks later. Samples were analysed using 16S rRNA gene sequencing, UPLC-MS and qRT-PCR. RESULTS The microbiota and bile acid profile showed distinct changes at each timepoint. The inflammatory response became apparent at weeks 12 and 24. Moreover, significant correlations between individual taxa, cytokines and bile acids were detected. One co-abundance group (CAG) differed significantly between PBS- and AOM-treated mice at week 24. Correlation analysis also revealed significant associations between CAGs, bile acids and the bile acid transporter, ASBT. Aberrant crypt foci and adenomas were first detectable at weeks 24 and 48, respectively. CONCLUSION The observed changes precede host hyperplastic transformation and may represent early therapeutic targets for the prevention or management of CRC at specific timepoints in the tumorigenic process.
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Affiliation(s)
- J M Keane
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
- Department of Medicine, University College Cork, Cork, Ireland
- School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland
- Department of Physiology, University College Cork, Cork, Ireland
| | - C J Walsh
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - P Cronin
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland
| | - K Baker
- Department of Medicine, University College Cork, Cork, Ireland
- Department of Pathology, University College Cork, Cork, Ireland
| | - S Melgar
- APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - P D Cotter
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland
| | - S A Joyce
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland
| | - C G M Gahan
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
- School of Pharmacy, University College Cork, Cork, Ireland
| | - A Houston
- APC Microbiome Ireland, University College Cork, Cork, Ireland.
- Department of Medicine, University College Cork, Cork, Ireland.
| | - N P Hyland
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- Department of Physiology, University College Cork, Cork, Ireland
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16
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Hashimoto S, Tochio T, Funasaka K, Funahashi K, Hartanto T, Togashi Y, Saito M, Nishimoto Y, Yoshinori M, Nakaoka K, Watanabe A, Nagasaka M, Nakagawa Y, Miyahara R, Shibata T, Hirooka Y. Changes in intestinal bacteria and imbalances of metabolites induced in the intestines of pancreatic ductal adenocarcinoma patients in a Japanese population: a preliminary result. Scand J Gastroenterol 2023; 58:193-198. [PMID: 36036243 DOI: 10.1080/00365521.2022.2114812] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The relationship between pancreatic ductal adenocarcinoma (PDAC) and the intestinal environment is not fully understood. The purpose of this study was to elucidate the characteristics of the intestinal environment in PDAC. METHODS We performed a case-control study of 5 Japanese patients with unresectable PDAC located in the body or tail (PDAC-bt). The number of patients analyzed was limited for this preliminary study. We included 68 healthy subjects, herein control, of pre-printed study in the preliminary study. 16S rRNA amplicon sequencing and metabolomic analysis were performed using fecal samples from the subjects. RESULTS There was no difference in the Shannon index and Principal Coordinate Analysis between PDAC-bt and the control. However, a significant increase in oral-associated bacteria (Actinomyces, Streptococcus, Veillonella, Lactobacillus) was observed. A significant decrease of Anaerostipes was demonstrated in the feces of PDAC-bt compared with the control. The intestinal propionic acid and deoxycholic acid were significantly lower in PDAC-bt compared with the control. CONCLUSIONS We showed that the intestinal environment of PDAC-bt is characterized by an increase in oral-associated bacteria and an imbalance of metabolites but without changes in alpha and beta diversity of the gut microbiota profiles.Clinical Trial Registration: www.umin.ac.jp, UMIN 000041974, 000023675, 000023970.
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Affiliation(s)
- Senju Hashimoto
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | - Takumi Tochio
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | - Kohei Funasaka
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | | | | | - Yuka Togashi
- Metabologenomics, Inc, Tsuruoka, Yamagata, Japan
| | - Misa Saito
- Metabologenomics, Inc, Tsuruoka, Yamagata, Japan
| | | | | | - Kazunori Nakaoka
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | - Ayako Watanabe
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | - Mitsuo Nagasaka
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | - Yoshihito Nakagawa
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | - Ryoji Miyahara
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | - Tomoyuki Shibata
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
| | - Yoshiki Hirooka
- Department of Gastroenterology and Hepatology, Fujita Health University, Toyoake, Aichi, Japan
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17
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Gut Microbial-Derived Metabolites as Immune Modulators of T Helper 17 and Regulatory T Cells. Int J Mol Sci 2023; 24:ijms24021806. [PMID: 36675320 PMCID: PMC9867388 DOI: 10.3390/ijms24021806] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 01/10/2023] [Accepted: 01/12/2023] [Indexed: 01/18/2023] Open
Abstract
The gut microbiota and its derived metabolites greatly impact the host immune system, both innate and adaptive responses. Gut dysbiosis and altered levels of microbiota-derived metabolites have been described in several immune-related and immune-mediated diseases such as intestinal bowel disease, multiple sclerosis, or colorectal cancer. Gut microbial-derived metabolites are synthesized from dietary compounds ingested by the host or host-produced metabolites, and additionally, some bacterial products can be synthesized de novo. In this review, we focus on the two first metabolites families including short-chain fatty acids, indole metabolites, polyamines, choline-derived compounds, and secondary bile acids. They all have been described as immunoregulatory molecules that specifically affect the adaptive immune system and T helper 17 and regulatory T cells. We discuss the mechanisms of action and the consequences in health and diseases related to these gut microbial-derived metabolites. Finally, we propose that the exogenous administration of these molecules or other compounds that bind to their immunoregulatory receptors in a homologous manner could be considered therapeutic approaches.
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18
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Kumar A, Ali A, Kapardar RK, Dar GM, Nimisha, Apurva, Sharma AK, Verma R, Sattar RSA, Ahmad E, Mahajan B, Saluja SS. Implication of gut microbes and its metabolites in colorectal cancer. J Cancer Res Clin Oncol 2023; 149:441-465. [PMID: 36572792 DOI: 10.1007/s00432-022-04422-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 10/14/2022] [Indexed: 12/28/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is the third most common cancer with a significant impact on loss of life. In 2020, nearly 1.9 million new cases and over 9,35,000 deaths were reported. Numerous microbes that are abundant in the human gut benefit host physiology in many ways. Although the underlying mechanism is still unknown, their association appears to be crucial in the beginning and progression of CRC. Diet has a significant impact on the microbial composition and may increase the chance of getting CRC. Increasing evidence points to the gut microbiota as the primary initiator of colonic inflammation, which is connected to the development of colonic tumors. However, it is unclear how the microbiota contributes to the development of CRCs. Patients with CRC have been found to have dysbiosis of the gut microbiota, which can be identified by a decline in commensal bacterial species, such as those that produce butyrate, and a concurrent increase in harmful bacterial populations, such as opportunistic pathogens that produce pro-inflammatory cytokines. We believe that using probiotics or altering the gut microbiota will likely be effective tools in the fight against CRC treatment. PURPOSE In this review, we revisited the association between gut microbiota and colorectal cancer whether cause or effect. The various factors which influence gut microbiome in patients with CRC and possible mechanism in relation with development of CRC. CONCLUSION The clinical significance of the intestinal microbiota may aid in the prevention and management of CRC.
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Affiliation(s)
- Arun Kumar
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Asgar Ali
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Raj Kishore Kapardar
- Microbial Biotechnology Division, The Energy and Resource Institute (TERI), New Delhi, India
| | - Ghulam Mehdi Dar
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Nimisha
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Apurva
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Abhay Kumar Sharma
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Renu Verma
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Real Sumayya Abdul Sattar
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Ejaj Ahmad
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Bhawna Mahajan
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
- Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India
| | - Sundeep Singh Saluja
- Central Molecular Laboratory, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India.
- Department of GI Surgery, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research (GIPMER), New Delhi, India.
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19
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Nami Y, Hejazi S, Geranmayeh MH, Shahgolzari M, Yari Khosroushahi A. Probiotic immunonutrition impacts on colon cancer immunotherapy and prevention. Eur J Cancer Prev 2023; 32:30-47. [PMID: 36134612 DOI: 10.1097/cej.0000000000000738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The important role of the immune system in treating cancer has attracted the attention of researchers to the emergence of oncology research. Immunotherapy has shown that the immune system is important in the fight against cancer. The challenge has led researchers to analyze the impact of immunotherapy on improving the status of the immune system, modifying the resulting safety response, reducing toxicity, and improving the results. This study aimed to discuss the potential mechanisms of probiotics in preventing colon cancer. The mechanisms include the change in intestinal microbiota, the metabolic activity of microbiota, the binding and degradation of the carcinogenic compounds present in the lumen of the intestine, the production of compounds with anticancer activity, immune system modification, intestinal dysfunction, changes in host physiology, and inhibition of cell proliferation and induction of apoptosis in cancerous cells. By contrast, very few reports have shown the harmful effects of oral probiotic supplements. According to available evidence, further studies on probiotics are needed, especially in identifying bacterial species with anticancer potential, studying the survival of the strains after passing the digestive tract, reviewing potential side effects in people with a weak immune system, and ultimately consuming and repeating its use. This study emphasizes that the nutritional formula can modulate inflammatory and immune responses in cancer patients. This effect reduces acute toxicity, although the pathways and measurement of this immune response are unclear. Nutrition safety is an emerging field in oncology, and further research is required.
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Affiliation(s)
- Yousef Nami
- Department of Food Biotechnology, Branch for Northwest & West Region, Agricultural Biotechnology Research Institute of Iran, Agricultural Research, Education and Extension Organization (AREEO)
| | - Salva Hejazi
- Department of Medicine, Student Research Committee, Tabriz University of Medical Sciences
| | - Mohammad Hossein Geranmayeh
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
| | - Mehdi Shahgolzari
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
- Biotechnology Research Center, Tabriz University of Medical Sciences
| | - Ahmad Yari Khosroushahi
- Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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20
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Gomes S, Baltazar F, Silva E, Preto A. Microbiota-Derived Short-Chain Fatty Acids: New Road in Colorectal Cancer Therapy. Pharmaceutics 2022; 14:2359. [PMID: 36365177 PMCID: PMC9698921 DOI: 10.3390/pharmaceutics14112359] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 10/28/2022] [Accepted: 10/28/2022] [Indexed: 08/13/2023] Open
Abstract
The colon microbiota is an important player in colorectal cancer (CRC) development, which is responsible for most of the cancer-related deaths worldwide. During carcinogenesis, the colon microbiota composition changes from a normobiosis profile to dysbiosis, interfering with the production of short-chain fatty acids (SCFAs). Each SCFA is known to play a role in several biological processes but, despite their reported individual effects, colon cells are exposed to these compounds simultaneously and the combined effect of SCFAs in colon cells is still unknown. Our aim was to explore the effects of SCFAs, alone or in combination, unveiling their biological impact on CRC cell phenotypes. We used a mathematical model for the prediction of the expected SCFA mixture effects and found that, when in mixture, SCFAs exhibit a concentration addition behavior. All SCFAs, alone or combined at the physiological proportions founded in the human colon, revealed to have a selective and anticancer effect by inhibiting colony formation and cell proliferation, increasing apoptosis, disturbing the energetic metabolism, inducing lysosomal membrane permeabilization, and decreasing cytosolic pH. We showed for the first time that SCFAs are specific towards colon cancer cells, showing promising therapeutic effects. These findings open a new road for the development of alternatives for CRC therapy based on the increase in SCFA levels through the modulation of the colon microbiota composition.
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Affiliation(s)
- Sara Gomes
- Centre of Molecular and Environmental Biology (CBMA), Department of Biology, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal
- Institute of Science and Innovation for Bio-Sustainability (IBS), University of Minho, 4710-054 Braga, Portugal
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-054 Braga, Portugal
- Department of Life Sciences, Brunel University (BU), London UB8 3PH, UK
| | - Fátima Baltazar
- Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-054 Braga, Portugal
- ICVS/3B’s PT Government Associate Laboratory, 4806-909 Braga/Guimarães, Portugal
| | - Elisabete Silva
- Department of Life Sciences, Brunel University (BU), London UB8 3PH, UK
| | - Ana Preto
- Centre of Molecular and Environmental Biology (CBMA), Department of Biology, Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal
- Institute of Science and Innovation for Bio-Sustainability (IBS), University of Minho, 4710-054 Braga, Portugal
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21
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Alvandi E, Wong WKM, Joglekar MV, Spring KJ, Hardikar AA. Short-chain fatty acid concentrations in the incidence and risk-stratification of colorectal cancer: a systematic review and meta-analysis. BMC Med 2022; 20:323. [PMID: 36184594 PMCID: PMC9528142 DOI: 10.1186/s12916-022-02529-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 08/15/2022] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND The beneficial role of gut microbiota and bacterial metabolites, including short-chain fatty acids (SCFAs), is well recognized, although the available literature around their role in colorectal cancer (CRC) has been inconsistent. METHODS We performed a systematic review and meta-analysis to examine the associations of fecal SCFA concentrations to the incidence and risk of CRC. Data extraction through Medline, Embase, and Web of Science was carried out from database conception to June 29, 2022. Predefined inclusion/exclusion criteria led to the selection of 17 case-control and six cross-sectional studies for quality assessment and analyses. Studies were categorized for CRC risk or incidence, and RevMan 5.4 was used to perform the meta-analyses. Standardized mean differences (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model. Studies lacking quantitation were included in qualitative analyses. RESULTS Combined analysis of acetic, propionic, and butyric acid revealed significantly lower concentrations of these SCFAs in individuals with a high-risk of CRC (SMD = 2.02, 95% CI 0.31 to 3.74, P = 0.02). Additionally, CRC incidence was higher in individuals with lower levels of SCFAs (SMD = 0.45, 95% CI 0.19 to 0.72, P = 0.0009), compared to healthy individuals. Qualitative analyses identified 70.4% of studies reporting significantly lower concentrations of fecal acetic, propionic, butyric acid, or total SCFAs in those at higher risk of CRC, while 66.7% reported significantly lower concentrations of fecal acetic and butyric acid in CRC patients compared to healthy controls. CONCLUSIONS Overall, lower fecal concentrations of the three major SCFAs are associated with higher risk of CRC and incidence of CRC.
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Affiliation(s)
- Ehsan Alvandi
- Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Medical Oncology Group, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
| | - Wilson K M Wong
- Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Translational Health Research Institute, Western Sydney University, Campbelltown, NSW, Australia
| | - Mugdha V Joglekar
- Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, NSW, Australia
- Translational Health Research Institute, Western Sydney University, Campbelltown, NSW, Australia
| | - Kevin J Spring
- Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
- South-West Sydney Clinical Campuses, UNSW Medicine & Health, Sydney, NSW, Australia.
- Liverpool Clinical School, School of Medicine, Western Sydney University, Liverpool, NSW, Australia.
| | - Anandwardhan A Hardikar
- Diabetes and Islet Biology Group, School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
- Translational Health Research Institute, Western Sydney University, Campbelltown, NSW, Australia.
- Department of Science and Environment, Roskilde University Copenhagen, Roskilde, Denmark.
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22
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Zhao Y, Nakatsu C, Jones-Hall Y, Jiang Q. Supplementation of polyphenol-rich grapes attenuates colitis, colitis-associated colon cancer and disease-associated dysbiosis in mice, but fails to mitigate colitis in antibiotic-treated mice. J Nutr Biochem 2022; 109:109124. [PMID: 35961465 DOI: 10.1016/j.jnutbio.2022.109124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Revised: 07/09/2022] [Accepted: 07/14/2022] [Indexed: 12/18/2022]
Abstract
Polyphenols are known to interact with gut microbes that play key roles in maintaining gut health, but the role of gut microbiota modulation by polyphenols in mitigating colonic diseases is not fully established. We hypothesize that the interaction of polyphenols with the gut microbiota contributes to the attenuation of colitis and colitis-associated colon cancer (CAC). To test this hypothesis, we examined the effects of dietary supplementation of polyphenol-rich grape powder (GP) on azoxymethane (AOM) and dextran sulfate sodium (DSS)-induced colitis, CAC and the gut microbiota in mice (study 1), and further compared anti-colitis effects of GP in regular and antibiotic-treated mice (study 2). Compared to the control diet that has matched non-polyphenol contents, 10% GP, but not 3% GP, attenuated AOM-DSS induced colitis and tumor multiplicity by 29% (p<0.05). Ten percent GP increased gut bacterial evenness and counteracted CAC-induced decrease of bacterial evenness and changes of microbial composition. Remarkably, gut bacterial functional profiles of healthy mice and diseased mice fed 10% GP were similar, and both were significantly different from those of diseased mice with the control diet. Furthermore, 10% GP increased the relative abundance of butyrate-producing bacteria in the Lachnospiraceae family and enhanced the concentrations of fecal butyrate. Additionally, 10% GP mitigated DSS-induced colitis in conventional mice, but not the antibiotic-treated, gut microbe-depleted mice. Collectively, our studies demonstrate that grape polyphenols alleviate colonic diseases and prevent disease-associated dysbiosis, and their interaction with the gut microbiota may play a causative role in the protection of gut health.
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Affiliation(s)
- Yiying Zhao
- Department of Nutrition Science, College of Health and Human Sciences, Purdue University, West Lafayette, IN
| | - Cindy Nakatsu
- Department of Agronomy, College of Agriculture, Purdue University, West Lafayette, IN
| | - Yava Jones-Hall
- Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX
| | - Qing Jiang
- Department of Nutrition Science, College of Health and Human Sciences, Purdue University, West Lafayette, IN.
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23
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Xing C, Du Y, Duan T, Nim K, Chu J, Wang HY, Wang RF. Interaction between microbiota and immunity and its implication in colorectal cancer. Front Immunol 2022; 13:963819. [PMID: 35967333 PMCID: PMC9373904 DOI: 10.3389/fimmu.2022.963819] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/08/2022] [Indexed: 11/13/2022] Open
Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the world. Besides genetic causes, colonic inflammation is one of the major risk factors for CRC development, which is synergistically regulated by multiple components, including innate and adaptive immune cells, cytokine signaling, and microbiota. The complex interaction between CRC and the gut microbiome has emerged as an important area of current CRC research. Metagenomic profiling has identified a number of prominent CRC-associated bacteria that are enriched in CRC patients, linking the microbiota composition to colitis and cancer development. Some microbiota species have been reported to promote colitis and CRC development in preclinical models, while a few others are identified as immune modulators to induce potent protective immunity against colitis and CRC. Mechanistically, microbiota regulates the activation of different immune cell populations, inflammation, and CRC via crosstalk between innate and adaptive immune signaling pathways, including nuclear factor kappa B (NF-κB), type I interferon, and inflammasome. In this review, we provide an overview of the potential interactions between gut microbiota and host immunity and how their crosstalk could synergistically regulate inflammation and CRC, thus highlighting the potential roles and mechanisms of gut microbiota in the development of microbiota-based therapies to prevent or alleviate colitis and CRC.
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Affiliation(s)
- Changsheng Xing
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Yang Du
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Tianhao Duan
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Kelly Nim
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Junjun Chu
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Helen Y. Wang
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
| | - Rong-Fu Wang
- Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
- Department of Pediatrics, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States
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24
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Colorectal cancer: risk factors and potential of dietary probiotics in its prevention. PROCEEDINGS OF THE INDIAN NATIONAL SCIENCE ACADEMY 2022. [DOI: 10.1007/s43538-022-00083-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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25
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Broadfield LA, Saigal A, Szamosi JC, Hammill JA, Bezverbnaya K, Wang D, Gautam J, Tsakiridis EE, Di Pastena F, McNicol J, Wu J, Syed S, Lally JSV, Raphenya AR, Blouin MJ, Pollak M, Sacconi A, Blandino G, McArthur AG, Schertzer JD, Surette MG, Collins SM, Bramson JL, Muti P, Tsakiridis T, Steinberg GR. Metformin-induced reductions in tumor growth involves modulation of the gut microbiome. Mol Metab 2022; 61:101498. [PMID: 35452877 PMCID: PMC9096669 DOI: 10.1016/j.molmet.2022.101498] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/25/2022] [Accepted: 04/11/2022] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND/PURPOSE Type 2 diabetes and obesity increase the risk of developing colorectal cancer. Metformin may reduce colorectal cancer but the mechanisms mediating this effect remain unclear. In mice and humans, a high-fat diet (HFD), obesity and metformin are known to alter the gut microbiome but whether this is important for influencing tumor growth is not known. METHODS Mice with syngeneic MC38 colon adenocarcinomas were treated with metformin or feces obtained from control or metformin treated mice. RESULTS We find that compared to chow-fed controls, tumor growth is increased when mice are fed a HFD and that this acceleration of tumor growth can be partially recapitulated through transfer of the fecal microbiome or in vitro treatment of cells with fecal filtrates from HFD-fed animals. Treatment of HFD-fed mice with orally ingested, but not intraperitoneally injected, metformin suppresses tumor growth and increases the expression of short-chain fatty acid (SCFA)-producing microbes Alistipes, Lachnospiraceae and Ruminococcaceae. The transfer of the gut microbiome from mice treated orally with metformin to drug naïve, conventionalized HFD-fed mice increases circulating propionate and butyrate, reduces tumor proliferation, and suppresses the expression of sterol response element binding protein (SREBP) gene targets in the tumor. CONCLUSION These data indicate that in obese mice fed a HFD, metformin reduces tumor burden through changes in the gut microbiome.
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Affiliation(s)
- Lindsay A Broadfield
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Amna Saigal
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada
| | - Jake C Szamosi
- Farncombe Family Digestive Research Institute, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
| | - Joanne A Hammill
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Ksenia Bezverbnaya
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Dongdong Wang
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Jaya Gautam
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Evangelia E Tsakiridis
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Fiorella Di Pastena
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Jamie McNicol
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Jianhan Wu
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Saad Syed
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada; Farncombe Family Digestive Research Institute, McMaster University, Hamilton, ON, Canada
| | - James S V Lally
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Amogelang R Raphenya
- Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
| | - Marie-Jose Blouin
- Segal Cancer Center, Lady Davis Institute for Medical Research, Jewish General Hospital; Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada
| | - Michael Pollak
- Segal Cancer Center, Lady Davis Institute for Medical Research, Jewish General Hospital; Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada
| | - Andrea Sacconi
- Oncogenomic and Epigenetic Unit, Italian National Cancer Institute "Regina Elena", Rome, Italy
| | - Giovanni Blandino
- Oncogenomic and Epigenetic Unit, Italian National Cancer Institute "Regina Elena", Rome, Italy
| | - Andrew G McArthur
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
| | - Jonathan D Schertzer
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Farncombe Family Digestive Research Institute, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
| | - Michael G Surette
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada; Farncombe Family Digestive Research Institute, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada
| | - Stephen M Collins
- Department of Medicine, McMaster University, Hamilton, ON, Canada; Farncombe Family Digestive Research Institute, McMaster University, Hamilton, ON, Canada
| | - Jonathan L Bramson
- Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
| | - Paola Muti
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Oncology, McMaster University, Hamilton, ON, Canada
| | - Theodoros Tsakiridis
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Oncology, McMaster University, Hamilton, ON, Canada
| | - Gregory R Steinberg
- Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
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26
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Relationship between gut microbiota and colorectal cancer: Probiotics as a potential strategy for prevention. Food Res Int 2022; 156:111327. [DOI: 10.1016/j.foodres.2022.111327] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/27/2022] [Accepted: 04/28/2022] [Indexed: 12/15/2022]
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27
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The interplay between anticancer challenges and the microbial communities from the gut. Eur J Clin Microbiol Infect Dis 2022; 41:691-711. [PMID: 35353280 DOI: 10.1007/s10096-022-04435-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 03/15/2022] [Indexed: 11/03/2022]
Abstract
Cancer being an increasing burden on human health, the use of anticancer drugs has risen over the last decades. The physiological effects of these drugs are not only perceived by the host's cells but also by the microbial cells it harbors as commensals, notably the gut microbiota. Since the early '50 s, the cytotoxicity of anticancer chemotherapy was evaluated on bacteria revealing some antimicrobial activities that result in an established perturbation of the gut microbiota. This perturbation can affect the host's health through dysbiosis, which can lead to multiple complications, but has also been shown to have a direct effect on the treatment efficiency.We, therefore, conducted a review of literature focusing on this triangular relationship involving the microbial communities from the gut, the host's disease, and the anticancer treatment. We focused specifically on the antimicrobial effects of anticancer chemotherapy, their impact on mutagenesis in bacteria, and the perspectives of using bacteria-based tools to help in the diagnostic and treatment of cancer.
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28
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Yu L, Zhao G, Wang L, Zhou X, Sun J, Li X, Zhu Y, He Y, Kofonikolas K, Bogaert D, Dunlop M, Zhu Y, Theodoratou E, Li X. A systematic review of microbial markers for risk prediction of colorectal neoplasia. Br J Cancer 2022; 126:1318-1328. [PMID: 35292756 PMCID: PMC9042911 DOI: 10.1038/s41416-022-01740-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 12/23/2021] [Accepted: 02/03/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Substantial evidence indicates that dysbiosis of the gut microbial community is associated with colorectal neoplasia. This review aims to systematically summarise the microbial markers associated with colorectal neoplasia and to assess their predictive performance. METHODS A comprehensive literature search of MEDLINE and EMBASE databases was performed to identify eligible studies. Observational studies exploring the associations between microbial biomarkers and colorectal neoplasia were included. We also included prediction studies that constructed models using microbial markers to predict CRC and adenomas. Risk of bias for included observational and prediction studies was assessed. RESULTS Forty-five studies were included to assess the associations between microbial markers and colorectal neoplasia. Nine faecal microbiotas (i.e., Fusobacterium, Enterococcus, Porphyromonas, Salmonella, Pseudomonas, Peptostreptococcus, Actinomyces, Bifidobacterium and Roseburia), two oral pathogens (i.e., Treponema denticola and Prevotella intermedia) and serum antibody levels response to Streptococcus gallolyticus subspecies gallolyticus were found to be consistently associated with colorectal neoplasia. Thirty studies reported prediction models using microbial markers, and 83.3% of these models had acceptable-to-good discrimination (AUROC > 0.75). The results of predictive performance were promising, but most of the studies were limited to small number of cases (range: 9-485 cases) and lack of independent external validation (76.7%). CONCLUSIONS This review provides insight into the evidence supporting the association between different types of microbial species and their predictive value for colorectal neoplasia. Prediction models developed from case-control studies require further external validation in high-quality prospective studies. Further studies should assess the feasibility and impact of incorporating microbial biomarkers in CRC screening programme.
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Affiliation(s)
- Lili Yu
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Gang Zhao
- Center for Disease Control and Prevention of Hangzhou, Hangzhou, China
| | - Lijuan Wang
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xuan Zhou
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jing Sun
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xinxuan Li
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yingshuang Zhu
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Yazhou He
- Department of Oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Sichuan, China
| | | | - Debby Bogaert
- Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
| | - Malcolm Dunlop
- Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
| | - Yimin Zhu
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Evropi Theodoratou
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK
- Cancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
| | - Xue Li
- Department of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
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29
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Zheng AR, Wei CK, Ni ZJ, Thakur K, Zhang JG, Wei ZJ. Gut modulatory effects of flaxseed derived Maillard reaction products in Sprague-Dawley rats during sub-chronic toxicity. Food Chem Toxicol 2022; 165:113115. [DOI: 10.1016/j.fct.2022.113115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/25/2022] [Accepted: 05/04/2022] [Indexed: 11/28/2022]
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30
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Bartolucci G, Pallecchi M, Menicatti M, Moracci L, Pucciarelli S, Agostini M, Crotti S. A method for assessing plasma free fatty acids from C2 to C18 and its application for the early detection of colorectal cancer. J Pharm Biomed Anal 2022; 215:114762. [DOI: 10.1016/j.jpba.2022.114762] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Revised: 03/31/2022] [Accepted: 04/05/2022] [Indexed: 12/19/2022]
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31
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Ozato N, Yamaguchi T, Mori K, Katashima M, Kumagai M, Murashita K, Katsuragi Y, Tamada Y, Kakuta M, Imoto S, Ihara K, Nakaji S. Two Blautia Species Associated with Visceral Fat Accumulation: A One-Year Longitudinal Study. BIOLOGY 2022; 11:biology11020318. [PMID: 35205184 PMCID: PMC8869763 DOI: 10.3390/biology11020318] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 02/14/2022] [Accepted: 02/14/2022] [Indexed: 12/14/2022]
Abstract
Simple Summary Intestinal microflora has been associated with obesity. While cardiovascular disorders are more strongly associated with visceral fat than the body mass index (BMI), the link between visceral fat area (VFA) and intestinal microflora has been little studied. In this study, we investigated the association between intestinal microflora and VFA and BMI using a longitudinal study (N = 767). We found that the intestinal microflora composition is significantly associated with VFA or BMI; however, the associated gut microbes differ. Furthermore, two gut species—Blautia hansenii and Blautia producta—were significantly and negatively associated with VFA accumulation. Abstract Intestinal microflora has been associated with obesity. While visceral fat is more strongly associated with cardiovascular disorder, a complication linked to obesity, than the body mass index (BMI), the association between intestinal microflora and obesity (as defined in terms of BMI) has been studied widely. However, the link between visceral fat area (VFA) and intestinal microflora has been little studied. In this study, we investigate the association between intestinal microflora and VFA and BMI using a longitudinal study on Japanese subjects with different VFA statuses (N = 767). Principal component analysis of the changes in intestinal microflora composition over the one-year study period revealed the different associations between intestinal microflora and VFA and BMI. As determined by 16S rRNA amplicon sequencing, changes in the abundance ratio of two microbial genera—Blautia and Flavonifractor—were significantly associated with VFA changes and changes in the abundance ratio of four different microbial genera were significantly associated with BMI changes, suggesting that the associated intestinal microbes are different. Furthermore, as determined by metagenomic shotgun sequences, changes in the abundance ratios of two Blautia species—Blautia hansenii and Blautia producta—were significantly and negatively associated with VFA changes. Our findings might be used to develop a new treatment for visceral fat.
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Affiliation(s)
- Naoki Ozato
- Department of Active Life Promotion Sciences, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (K.M.); (M.K.); (M.K.); (Y.K.)
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan;
- Correspondence: ; Tel.: +81-172-395-041
| | - Tohru Yamaguchi
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan;
| | - Kenta Mori
- Department of Active Life Promotion Sciences, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (K.M.); (M.K.); (M.K.); (Y.K.)
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan;
| | - Mitsuhiro Katashima
- Department of Active Life Promotion Sciences, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (K.M.); (M.K.); (M.K.); (Y.K.)
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan;
| | - Mika Kumagai
- Department of Active Life Promotion Sciences, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (K.M.); (M.K.); (M.K.); (Y.K.)
| | - Koichi Murashita
- COI Research Initiatives Organization, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan;
| | - Yoshihisa Katsuragi
- Department of Active Life Promotion Sciences, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (K.M.); (M.K.); (M.K.); (Y.K.)
- Health & Wellness Products Research Laboratories, Kao Corporation, Tokyo 131-8501, Japan;
| | - Yoshinori Tamada
- Innovation Center for Health Promotion, Hirosaki University, Hirosaki City 036-8562, Japan;
| | - Masanori Kakuta
- Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 113-8654, Japan; (M.K.); (S.I.)
- M&D Data Science Center, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Seiya Imoto
- Innovation Center for Health Promotion, Hirosaki University, Hirosaki City 036-8562, Japan;
| | - Kazushige Ihara
- Department of Social Medicine, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (K.I.); (S.N.)
| | - Shigeyuki Nakaji
- Department of Social Medicine, Graduate School of Medicine, Hirosaki University, Hirosaki City 036-8562, Japan; (K.I.); (S.N.)
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Han L, Azad MAK, Huang P, Wang W, Zhang W, Blachier F, Kong X. Maternal Supplementation With Different Probiotic Mixture From Late Pregnancy to Day 21 Postpartum: Consequences for Litter Size, Plasma and Colostrum Parameters, and Fecal Microbiota and Metabolites in Sows. Front Vet Sci 2022; 9:726276. [PMID: 35211537 PMCID: PMC8860973 DOI: 10.3389/fvets.2022.726276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 01/17/2022] [Indexed: 11/13/2022] Open
Abstract
The present study determined the effects of different probiotic mixture supplementation to sows from late pregnancy to day 21 postpartum on reproductive performance, colostrum composition, plasma biochemical parameters, and fecal microbiota and metabolites. A total of 80 pregnant sows were randomly assigned to one of four groups (20 sows per group). The sows in the control group (CON group) were fed a basal diet, and those in the BS-A+B, BS-A+BL, and BS-B+BL groups were fed basal diets supplemented with 250 g/t of different probiotic mixture containing either 125 g/t of Bacillus subtilis A (BS-A), Bacillus subtilis B (BS-B), and/or Bacillus licheniformis (BL), respectively. The trial period was from day 85 of pregnancy to day 21 postpartum. The results showed that different dietary probiotic mixture supplementation increased (P < 0.05) the average weaning weight and average daily gain of piglets, while dietary BS-A+BL supplementation increased the number of weaned piglets (P < 0.05), litter weight (P = 0.06), litter weight gain (P = 0.06), and litter daily gain (P = 0.06) at weaning compared with the CON group. Different dietary probiotic mixture supplementation improved (P < 0.05) the colostrum quality by increasing the fat and dry matter concentrations, as well as the protein and urea nitrogen concentrations in the BS-A+BL group. Dietary probiotic mixture BS-B+BL increased the plasma total protein on days 1 and 21 postpartum while decreased the plasma albumin on day 1 postpartum (P < 0.05). In addition, the plasma high-density lipoprotein-cholesterol was increased in the BS-A+B and BS-B+BL groups on day 21 postpartum, while plasma ammonia was decreased in the BS-A+B and BS-A+BL groups on day 1 and in the three probiotic mixtures groups on day 21 postpartum (P < 0.05). Dietary supplementation with different probiotic mixture also modified the fecal microbiota composition and metabolic activity in sows during pregnancy and postpartum stages. Collectively, these findings suggest that maternal supplementation with Bacillus subtilis in combination with Bacillus licheniformis are promising strategies for improving the reproductive performance and the overall health indicators in sows, as well as the growth of their offspring.
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Affiliation(s)
- Li Han
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Md. Abul Kalam Azad
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Pan Huang
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
| | - Wei Wang
- The Institute of Cell Transplantion and Gene Therapy, Centra-South University, the Engineering Center for Xenotransplantation, Changsha, China
| | | | - Francois Blachier
- UMR PNCA, INRAE, AgroParisTech, Université Paris-Saclay, Paris, France
| | - Xiangfeng Kong
- Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China
- *Correspondence: Xiangfeng Kong
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Yüksekal G, Sevimli Dikicier B, Koku Aydın B, Yılmaz K, Altındiş M, Köroğlu M. Investigation of intestinal microbiome in chronic spontaneous urticaria patients. Int J Dermatol 2022; 61:988-994. [PMID: 35100439 DOI: 10.1111/ijd.16054] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 11/16/2021] [Accepted: 12/17/2021] [Indexed: 01/14/2023]
Abstract
BACKGROUND Chronic urticaria is a disorder characterized by itchy erythematous plaques with edema lasting 6 weeks or more. The prevalence is 1%, and two thirds of these cases are "chronic spontaneous urticaria (CSU)." Drugs, food, infections, and systemic diseases may be etiologic factors for CSU, although it may be idiopathic. OBJECTIVES The aim of this study was to compare the diversity and distribution of the intestinal microbiome in CSU patients with that of healthy individuals. The hypothesis was to determine the probable association of intestinal microbiome with CSU. METHODS This study was conducted in Sakarya University Training and Research Hospital, Department of Dermatology. In this study, 20 CSU patients and 10 healthy volunteers were included. Stool samples were collected from all participants. 16S RNA sequencing and bioinformatic analysis were performed after isolation of DNA isolation from all samples. RESULTS Diversity in microorganisms, stool pH averages, Bristol scores, and the ratio of Firmicutes/Bacteroidetes were the significant changes between the two groups. LIMITATIONS Due to high cost involved in microbiota studies, only a limited number of patients and volunteers participated. CONCLUSION The alteration in the intestinal microbiota (dysbiosis) may be an essential factor for CSU development and may explain idiopathic cases.
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Affiliation(s)
- Gülcan Yüksekal
- Department of Dermatology, Yenikent State Hospital, Sakarya, Turkey
| | | | - Büşra Koku Aydın
- Department of Dermatology, Sakarya University Medical School, Sakarya, Turkey
| | - Kerem Yılmaz
- Department of Medical Microbiology, Sakarya University Medical School, Sakarya, Turkey
| | - Mustafa Altındiş
- Department of Medical Microbiology, Sakarya University Medical School, Sakarya, Turkey
| | - Mehmet Köroğlu
- Department of Medical Microbiology, Sakarya University Medical School, Sakarya, Turkey
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34
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Amoah YS, Rajasekharan SK, Reifen R, Shemesh M. Chickpea-Derived Prebiotic Substances Trigger Biofilm Formation by Bacillus subtilis. Nutrients 2021; 13:nu13124228. [PMID: 34959781 PMCID: PMC8704855 DOI: 10.3390/nu13124228] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 11/19/2021] [Accepted: 11/21/2021] [Indexed: 11/16/2022] Open
Abstract
Chickpea-based foods are known for their low allergenicity and rich nutritional package. As an essential dietary legume, chickpea is often processed into milk or hummus or as an industrial source of protein and starch. The current study explores the feasibility of using the chickpea-derived prebiotic substances as a scaffold for growing Bacillus subtilis (a prospective probiotic bacterium) to develop synbiotic chickpea-based functional food. We report that the chickpea-derived fibers enhance the formation of the B. subtilis biofilms and the production of the antimicrobial pigment pulcherrimin. Furthermore, electron micrograph imaging confirms the bacterial embedding onto the chickpea fibers, which may provide a survival tactic to shield and protect the bacterial population from environmental insults. Overall, it is believed that chickpea-derived prebiotic substances provide a staple basis for developing functional probiotics and synbiotic food.
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Affiliation(s)
- Yaa Serwaah Amoah
- Department of Food Sciences, Institute for Postharvest Technology and Food Sciences, Agricultural Research Organization (ARO), Volcani Institute, Rishon LeZion 7528809, Israel; (Y.S.A.); (S.K.R.)
- The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel;
| | - Satish Kumar Rajasekharan
- Department of Food Sciences, Institute for Postharvest Technology and Food Sciences, Agricultural Research Organization (ARO), Volcani Institute, Rishon LeZion 7528809, Israel; (Y.S.A.); (S.K.R.)
| | - Ram Reifen
- The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel;
| | - Moshe Shemesh
- Department of Food Sciences, Institute for Postharvest Technology and Food Sciences, Agricultural Research Organization (ARO), Volcani Institute, Rishon LeZion 7528809, Israel; (Y.S.A.); (S.K.R.)
- Correspondence:
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35
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Zhang M, Wang Y, Zhao X, Liu C, Wang B, Zhou J. Mechanistic basis and preliminary practice of butyric acid and butyrate sodium to mitigate gut inflammatory diseases: a comprehensive review. Nutr Res 2021; 95:1-18. [PMID: 34757305 DOI: 10.1016/j.nutres.2021.08.007] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 08/19/2021] [Accepted: 08/26/2021] [Indexed: 01/02/2023]
Abstract
A key event featured in the early stage of chronic gut inflammatory diseases is the disordered recruitment and excess accumulation of immune cells in the gut lamina propria. This process is followed by the over-secretion of pro-inflammatory factors and the prolonged overactive inflammatory responses. Growing evidence has suggested that gut inflammatory diseases may be mitigated by butyric acid (BA) or butyrate sodium (NaB). Laboratory studies show that BA and NaB can enhance gut innate immune function through G-protein-mediated signaling pathways while mitigating the overactive inflammatory responses by inhibiting histone deacetylase. The regulatory effects may occur in both epithelial enterocytes and the immune cells in the lamina propria. Prior to further clinical trials, comprehensive literature reviews and rigid examination concerning the underlying mechanism are necessary. To this end, we collected and reviewed 197 published reports regarding the mechanisms, bioactivities, and clinical effects of BA and NaB to modulate gut inflammatory diseases. Our review found insufficient evidence to guarantee the safety of clinical practice of BA and NaB, either by anal enema or oral administration of capsule or tablet. The safety of clinical use of BA and NaB should be further evaluated. Alternatively, dietary patterns rich in "fruits, vegetables and beans" may be an effective and safe approach to prevent gut inflammatory disease, which elevates gut microbiota-dependent production of BA. Our review provides a comprehensive reference to future clinical trials of BA and NaB to treat gut inflammatory diseases.
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Affiliation(s)
- Mingbao Zhang
- Department of Gastroenterology and Hepatology, Second Hospital of Shandong University, Shandong University, 250012 China
| | - Yanan Wang
- Department of Gastroenterology and Hepatology, Second Hospital of Shandong University, Shandong University, 250012 China
| | - Xianqi Zhao
- School of Public Health, Cheeloo College of Medicine, Shandong University, 250012 China
| | - Chang Liu
- School of Public Health, Cheeloo College of Medicine, Shandong University, 250012 China
| | - Baozhen Wang
- Department of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, 250012 China.
| | - Jun Zhou
- Department of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, 250012 China.
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36
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Shimizu H, Arai K, Asahara T, Takahashi T, Tsuji H, Matsumoto S, Takeuchi I, Kyodo R, Yamashiro Y. Stool preparation under anaerobic conditions contributes to retention of obligate anaerobes: potential improvement for fecal microbiota transplantation. BMC Microbiol 2021; 21:275. [PMID: 34627158 PMCID: PMC8501685 DOI: 10.1186/s12866-021-02325-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2021] [Accepted: 09/20/2021] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Fecal microbiota transplantation (FMT) in patients with ulcerative colitis has shown variable efficacy depending on the protocol used. A previous randomized controlled trial reported that anaerobic preparation of donor stool contributes to improved efficacy. Despite the suggestion that viable obligate anaerobes would be decreased through aerobic handling, there have been only a limited number of reports on how these aerobic or anaerobic procedures affect the composition of viable microbiota in the fecal slurries used for FMT. METHODS We adopted 16S and 23S rRNA-targeted reverse transcription-quantitative polymerase chain reaction to quantify viable bacteria in fecal slurries. This study utilized specific primers designed to detect obligate anaerobes (including Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Bifidobacterium, Atopobium cluster, and Prevotella) and facultative anaerobes (including total lactobacilli, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus). We then calculated the ratio change (RC) between before and after mixing, and compared the resulting values between anaerobic-prep and aerobic-prep in samples fixed immediately after blending (RCAn0 vs. RCAe0) and in samples maintained (under anaerobic or aerobic conditions) for 1 h after blending (RCAn1 vs. RCAe1). RESULTS For most obligate anaerobes, the median RC tended to be less than 1, indicating that the number of obligate anaerobes was decreased by the blending procedure. However, in samples maintained for 1 h after blending, anaerobic-prep counteracted the decrease otherwise seen for the C. coccoides group and B. fragilis groups (P < 0.01 for both). The C. leptum subgroup also tended to show higher RC by anaerobic-prep than by aerobic-prep, although this effect was not statistically significant. Among facultative anaerobes, Enterobacteriaceae, Enterococcus, and Staphylococcus showed median RC values of more than 1, indicating that these organisms survived and even grew after mixing. Moreover, oxygen exposure had no significant influence on the survival of the facultative anaerobes. CONCLUSIONS The conditions under which the blending procedure was performed affected the proportion of live anaerobes in fecal slurries. The obligate anaerobes tended to be decreased by blending processes, but anaerobic-prep significantly mitigated this effect. Anaerobic-prep may improve the efficacy of FMT by permitting the efficient transfer of obligate anaerobes to patients with ulcerative colitis.
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Affiliation(s)
- Hirotaka Shimizu
- Division of Gastroenterology, Department of Medical Specialty, National Center for Child Health and Development, Tokyo, Japan. .,Department of Pediatrics and Adolescent Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan.
| | - Katsuhiro Arai
- Division of Gastroenterology, Department of Medical Specialty, National Center for Child Health and Development, Tokyo, Japan
| | - Takashi Asahara
- Yakult Central Institute, Tokyo, Japan.,Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Takuya Takahashi
- Yakult Central Institute, Tokyo, Japan.,Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Hirokazu Tsuji
- Yakult Central Institute, Tokyo, Japan.,Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Satoshi Matsumoto
- Yakult Central Institute, Tokyo, Japan.,Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Ichiro Takeuchi
- Division of Gastroenterology, Department of Medical Specialty, National Center for Child Health and Development, Tokyo, Japan.,Department of Pediatrics and Adolescent Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Reiko Kyodo
- Division of Gastroenterology, Department of Medical Specialty, National Center for Child Health and Development, Tokyo, Japan.,Department of Pediatrics and Adolescent Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Yuichiro Yamashiro
- Probiotics Research Laboratory, Juntendo University Graduate School of Medicine, Tokyo, Japan
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37
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Smet A, Kupcinskas J, Link A, Hold GL, Bornschein J. The Role of Microbiota in Gastrointestinal Cancer and Cancer Treatment: Chance or Curse? Cell Mol Gastroenterol Hepatol 2021; 13:857-874. [PMID: 34506954 PMCID: PMC8803618 DOI: 10.1016/j.jcmgh.2021.08.013] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 08/18/2021] [Accepted: 08/18/2021] [Indexed: 02/08/2023]
Abstract
The gastrointestinal (GI) tract is home to a complex and dynamic community of microorganisms, comprising bacteria, archaea, viruses, yeast, and fungi. It is widely accepted that human health is shaped by these microbes and their collective microbial genome. This so-called second genome plays an important role in normal functioning of the host, contributing to processes involved in metabolism and immune modulation. Furthermore, the gut microbiota also is capable of generating energy and nutrients (eg, short-chain fatty acids and vitamins) that are otherwise inaccessible to the host and are essential for mucosal barrier homeostasis. In recent years, numerous studies have pointed toward microbial dysbiosis as a key driver in many GI conditions, including cancers. However, comprehensive mechanistic insights on how collectively gut microbes influence carcinogenesis remain limited. In addition to their role in carcinogenesis, the gut microbiota now has been shown to play a key role in influencing clinical outcomes to cancer immunotherapy, making them valuable targets in the treatment of cancer. It also is becoming apparent that, besides the gut microbiota's impact on therapeutic outcomes, cancer treatment may in turn influence GI microbiota composition. This review provides a comprehensive overview of microbial dysbiosis in GI cancers, specifically esophageal, gastric, and colorectal cancers, potential mechanisms of microbiota in carcinogenesis, and their implications in diagnostics and cancer treatment.
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Affiliation(s)
- Annemieke Smet
- Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences; Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium
| | - Juozas Kupcinskas
- Institute for Digestive Research, Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, Germany
| | - Georgina L Hold
- Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, Australia
| | - Jan Bornschein
- Translational Gastroenterology Unit, Nuffield Department of Experimental Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
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Sulaiman I, Wu BG, Li Y, Tsay JC, Sauthoff M, Scott AS, Ji K, Koralov SB, Weiden M, Clemente JC, Jones D, Huang YJ, Stringer KA, Zhang L, Geber A, Banakis S, Tipton L, Ghedin E, Segal LN. Functional lower airways genomic profiling of the microbiome to capture active microbial metabolism. Eur Respir J 2021; 58:13993003.03434-2020. [PMID: 33446604 DOI: 10.1183/13993003.03434-2020] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 12/19/2020] [Indexed: 12/31/2022]
Abstract
BACKGROUND Microbiome studies of the lower airways based on bacterial 16S rRNA gene sequencing assess microbial community structure but can only infer functional characteristics. Microbial products, such as short-chain fatty acids (SCFAs), in the lower airways have significant impact on the host's immune tone. Thus, functional approaches to the analyses of the microbiome are necessary. METHODS Here we used upper and lower airway samples from a research bronchoscopy smoker cohort. In addition, we validated our results in an experimental mouse model. We extended our microbiota characterisation beyond 16S rRNA gene sequencing with the use of whole-genome shotgun (WGS) and RNA metatranscriptome sequencing. SCFAs were also measured in lower airway samples and correlated with each of the sequencing datasets. In the mouse model, 16S rRNA gene and RNA metatranscriptome sequencing were performed. RESULTS Functional evaluations of the lower airway microbiota using inferred metagenome, WGS and metatranscriptome data were dissimilar. Comparison with measured levels of SCFAs shows that the inferred metagenome from the 16S rRNA gene sequencing data was poorly correlated, while better correlations were noted when SCFA levels were compared with WGS and metatranscriptome data. Modelling lower airway aspiration with oral commensals in a mouse model showed that the metatranscriptome most efficiently captures transient active microbial metabolism, which was overestimated by 16S rRNA gene sequencing. CONCLUSIONS Functional characterisation of the lower airway microbiota through metatranscriptome data identifies metabolically active organisms capable of producing metabolites with immunomodulatory capacity, such as SCFAs.
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Affiliation(s)
- Imran Sulaiman
- Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA
| | - Benjamin G Wu
- Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA
| | - Yonghua Li
- Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA
| | - Jun-Chieh Tsay
- Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA
| | - Maya Sauthoff
- Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA
| | - Adrienne S Scott
- Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA
| | - Kun Ji
- Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA
| | - Sergei B Koralov
- Dept of Pathology, New York University School of Medicine, New York, NY, USA
| | - Michael Weiden
- Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA
| | - Jose C Clemente
- Dept of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Drew Jones
- Dept of Biochemistry and Molecular Pharmacology and Dept of Radiation Oncology, New York University School of Medicine, New York, NY, USA
| | - Yvonne J Huang
- Division of Pulmonary and Critical Care Medicine, Dept of Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Kathleen A Stringer
- Dept of Clinical Pharmacy, College of Pharmacy, and Division of Pulmonary and Critical Care Medicine, Dept of Medicine, School of Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Lingdi Zhang
- Center for Genomics and Systems Biology, Dept of Biology, New York University, New York, NY, USA
| | - Adam Geber
- Center for Genomics and Systems Biology, Dept of Biology, New York University, New York, NY, USA
| | - Stephanie Banakis
- Center for Genomics and Systems Biology, Dept of Biology, New York University, New York, NY, USA
| | - Laura Tipton
- Center for Genomics and Systems Biology, Dept of Biology, New York University, New York, NY, USA
| | - Elodie Ghedin
- Center for Genomics and Systems Biology, Dept of Biology, New York University, New York, NY, USA.,Dept of Epidemiology, School of Global Public Health, New York University, New York, NY, USA
| | - Leopoldo N Segal
- Division of Pulmonary, Critical Care, and Sleep Medicine, Dept of Medicine, New York University School of Medicine, New York, NY, USA
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Oh YJ, Nam K, Kim Y, Lee SY, Kim HS, Kang JI, Lee SY, Hwang KT. Effect of a Nutritionally Balanced Diet Comprising Whole Grains and Vegetables Alone or in Combination with Probiotic Supplementation on the Gut Microbiota. Prev Nutr Food Sci 2021; 26:121-131. [PMID: 34316477 PMCID: PMC8276713 DOI: 10.3746/pnf.2021.26.2.121] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 04/04/2021] [Accepted: 04/19/2021] [Indexed: 11/23/2022] Open
Abstract
Dysbiosis is a microbial imbalance, which often causes diseases and can be triggered by diet. Here, we deter-mined the effect of a nutritionally balanced diet rich in vegetables and whole grains alone and/or in combination with probiotics on the gut microbiota of healthy adults. We conducted a parallel-group randomized trial enrolling 63 healthy participants who were administered either a balanced diet (B-diet group), a probiotic capsule containing Lactobacillus plantarum PMO 08 (probiotics group), or a balanced diet plus probiotic capsule (synbiotics group) once daily for 2 weeks. The gut microbiota of each participant was analyzed via 16S ribosomal RNA MiSeq-based sequencing. Gastrointestinal symptoms and defecation habits were evaluated using questionnaires. The B-diet group showed significantly reduced Firmicutes-to-Bacteroidetes ratio (P<0.05) and abundances of the genera Blautia (P<0.01), Dorea (P<0.05), and Lachnoclostridium (P<0.05). Furthermore, the abundance of Bacteroides increased (P<0.05) compared to baseline levels. In the synbiotics group, Lactobacillus abundance increased significantly (P<0.05) and defecation difficulty decreased (P<0.05), confirming a synergistic effect of combined intake. All groups showed a significant reduction in the abundance of Clostridiaceae (P<0.001) and alleviation of bloating symptoms (P<0.05). Moreover, the relative abundance of Faecalibacterium significantly increased in the probiotics group (P<0.05). Therefore, the individual or combined intake of a nutritionally balanced diet and L. plantarum PMO 08 beneficially modifies the gut microbiota with the potential to alleviate gastrointestinal symptoms and improve defecation habits.
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Affiliation(s)
- Young Joo Oh
- Pulmuone Co., Ltd., Seoul 06367, Korea.,Department of Food and Nutrition, and Research Institute of Human Ecology, Seoul National University, Seoul 08826, Korea
| | - Kisun Nam
- Pulmuone Co., Ltd., Seoul 06367, Korea
| | | | | | - Hyung Sook Kim
- Department of Food and Nutrition, The University of Suwon, Gyeonggi 18323, Korea
| | | | | | - Keum Taek Hwang
- Department of Food and Nutrition, and Research Institute of Human Ecology, Seoul National University, Seoul 08826, Korea
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40
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Watanabe D, Murakami H, Ohno H, Tanisawa K, Konishi K, Todoroki-Mori K, Tsunematsu Y, Sato M, Ogata Y, Miyoshi N, Kubota N, Kunisawa J, Wakabayashi K, Kubota T, Watanabe K, Miyachi M. Stool pattern is associated with not only the prevalence of tumorigenic bacteria isolated from fecal matter but also plasma and fecal fatty acids in healthy Japanese adults. BMC Microbiol 2021; 21:196. [PMID: 34182940 PMCID: PMC8240356 DOI: 10.1186/s12866-021-02255-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 06/09/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Colibactin-producing Escherichia coli containing polyketide synthase (pks+ E. coli) has been shown to be involved in colorectal cancer (CRC) development through gut microbiota analysis in animal models. Stool status has been associated with potentially adverse gut microbiome profiles from fecal analysis in adults. We examined the association between stool patterns and the prevalence of pks+ E. coli isolated from microbiota in fecal samples of 224 healthy Japanese individuals. RESULTS Stool patterns were determined through factorial analysis using a previously validated questionnaire that included stool frequency, volume, color, shape, and odor. Factor scores were classified into tertiles. The prevalence of pks+ E. coli was determined by using specific primers for pks+ E. coli in fecal samples. Plasma and fecal fatty acids were measured via gas chromatography-mass spectrometry. The prevalence of pks+ E. coli was 26.8%. Three stool patterns identified by factorial analysis accounted for 70.1% of all patterns seen (factor 1: lower frequency, darker color, and harder shape; factor 2: higher volume and softer shape; and factor 3: darker color and stronger odor). Multivariable-adjusted odds ratios (95% confidence intervals) of the prevalence of pks+ E. coli for the highest versus the lowest third of the factor 1 score was 3.16 (1.38 to 7.24; P for trend = 0.006). This stool pattern exhibited a significant positive correlation with fecal isobutyrate, isovalerate, valerate, and hexanoate but showed a significant negative correlation with plasma eicosenoic acid and α-linoleic acid, as well as fecal propionate and succinate. No other stool patterns were significant. CONCLUSIONS These results suggest that stool patterns may be useful in the evaluation of the presence of tumorigenic bacteria and fecal fatty acids through self-monitoring of stool status without the requirement for specialist technology or skill. Furthermore, it may provide valuable insight about effective strategies for the early discovery of CRC.
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Affiliation(s)
- Daiki Watanabe
- Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, 162-8636, Japan
| | - Haruka Murakami
- Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, 162-8636, Japan
| | - Harumi Ohno
- Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, 162-8636, Japan
| | - Kumpei Tanisawa
- Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, 162-8636, Japan
| | - Kana Konishi
- Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, 162-8636, Japan
| | - Kikue Todoroki-Mori
- Department of Clinical Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, 162-8636, Japan
| | - Yuta Tsunematsu
- Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan
| | - Michio Sato
- Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan
| | - Yuji Ogata
- Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan
| | - Noriyuki Miyoshi
- School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan
| | - Naoto Kubota
- Department of Clinical Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, 162-8636, Japan
| | - Jun Kunisawa
- Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Osaka, 567-0085, Japan
| | - Keiji Wakabayashi
- School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan
| | - Tetsuya Kubota
- Department of Clinical Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, 162-8636, Japan.,Intestinal Microbiota Project, Kanagawa Institute of Industrial Science and Technology, Kanagawa, 243-0435, Japan.,Division of Diabetes and Metabolism, The Institute for Medical Science, Asahi Life Foundation, Tokyo, 103-0002, Japan
| | - Kenji Watanabe
- Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 422-8526, Japan
| | - Motohiko Miyachi
- Department of Physical Activity Research, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Tokyo, 162-8636, Japan. .,Faculty of Sport Sciences, Waseda University, Saitama, 359-1192, Japan.
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41
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Bhaskaran NA, Kumar L. Treating colon cancers with a non-conventional yet strategic approach: An overview of various nanoparticulate systems. J Control Release 2021; 336:16-39. [PMID: 34118336 DOI: 10.1016/j.jconrel.2021.06.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 06/06/2021] [Accepted: 06/07/2021] [Indexed: 12/18/2022]
Abstract
Regardless of progress in therapy management which are developed for colon cancer (CC), it remains the third most common cause of mortality due to cancers around the world. Conventional medicines pose side effects due to untoward action on non-target cells. Their inability to deliver drugs to the affected regions of the colon locally, in a reproducible manner raises a concern towards the efficacy of therapy. In this regard, nanoparticles emerged as a promising drug delivery system due to their flexibility in designing, drug release modulation and cancer cell targeting. Not only are nanoparticles making their way into colon cancer research in the revolution of conventional onco-therapeutics, but they also offer promising scope in the development of colon cancer vaccines and theranostic tools. However, there are challenges with respect to drug delivery using nanoparticles, which may hamper the delivery of these novel carriers to the colon. The present review addresses recent advents in nanotechnology for colon-specific drug delivery (CDDS) which may help to overcome the existing challenges and intends to recognize futuristic potentials in the treatment of CC with CDDS.
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Affiliation(s)
- N A Bhaskaran
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Udupi, Karnataka, India
| | - L Kumar
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Udupi, Karnataka, India.
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42
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El-Sayed A, Aleya L, Kamel M. The link among microbiota, epigenetics, and disease development. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2021; 28:28926-28964. [PMID: 33860421 DOI: 10.1007/s11356-021-13862-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 04/06/2021] [Indexed: 06/12/2023]
Abstract
The microbiome is a community of various microorganisms that inhabit or live on the skin of humans/animals, sharing the body space with their hosts. It is a sort of complex ecosystem of trillions of commensals, symbiotic, and pathogenic microorganisms, including trillions of bacteria, archaea, protozoa, fungi, and viruses. The microbiota plays a role in the health and disease status of the host. Their number, species dominance, and viability are dynamic. Their long-term disturbance is usually accompanied by serious diseases such as metabolic disorders, cardiovascular diseases, or even cancer. While epigenetics is a term that refers to different stimuli that induce modifications in gene expression patterns without structural changes in the inherited DNA sequence, these changes can be reversible or even persist for several generations. Epigenetics can be described as cell memory that stores experience against internal and external factors. Results from multiple institutions have contributed to the role and close interaction of both microbiota and epigenetics in disease induction. Understanding the mechanisms of both players enables a better understanding of disease induction and development and also opens the horizon to revolutionary therapeutic approaches. The present review illustrates the roles of diet, microbiome, and epigenetics in the induction of several chronic diseases. In addition, it discusses the application of epigenetic data to develop diagnostic biomarkers and therapeutics and evaluate their safety for patients. Understanding the interaction among all these elements enables the development of innovative preventive/therapeutic approaches for disease control.
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Affiliation(s)
- Amr El-Sayed
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt
| | - Lotfi Aleya
- Chrono-Environnement Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, F-25030, Besançon Cedex, France
| | - Mohamed Kamel
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.
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Lu Y, Li N, Zhu X, Pan J, Wang Y, Lan Y, Li Y, Wang A, Sun J, Liu C. Comparative analysis of excretion of six major compounds of Polygonum orientale L. extract in urine, feces and bile under physiological and myocardial ischemia conditions in rats using UPLC-MS/MS. Biomed Chromatogr 2021; 35:e5174. [PMID: 33998022 DOI: 10.1002/bmc.5174] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 03/25/2021] [Accepted: 04/19/2021] [Indexed: 11/07/2022]
Abstract
Polygonum orientale L. is a traditional Chinese medicine having extensive pharmacological activities including antimyocardial ischemia (MI) injury properties. Isoorientin, orientin, vitexin, quercitrin, astragalin and protocatechuic acid are the main compounds in P. orientale extract. The aim of this study was to establish an ultra-performance liquid chromatography-tandem mass spectrometry method for the determination of the content of these compounds in urine, feces and bile samples simultaneously and application of the method in a comparative excretion study in normal and MI model rats after oral administration of P. orientale extract. Chromatographic seperation was conducted on an Agilent Eclipse Plus C18 column with the mobile phase consisting of 0.1% formic acid-acetonitrile and 0.1% formic acid-water. Negative ion multiple reaction monitoring mode was used for quantification. The six compounds had good linearity (r ≥ 0.9921) and acceptable accuracy ranging from 10.10 to -5.82% The relative standard deviations of within-day precision and inter-day precision were <10.45 and 13.44%, respectively. The extraction recovery of the six analytes ranged from 80.31 to 101.47% and the matrix effect was 82.56-102.88%, indicating that the preparations of sample collected form urine, feces and bile were stable throughout analysis. The excretion amount of the six analytes increased in both normal and MI model rats' urine, feces and bile in a 24 h period and became stable between 36 and 48 h after administration. The total excretion rate of six compounds was <5% in urine, feces and bile of normal and MI model rats. The excretion peak period for all compounds in MI rats was slower than that in normal rats. This excretion study provides insights for further application and research on P. orientale.
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Affiliation(s)
- Yuan Lu
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China
| | - Na Li
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China.,School of Pharmacy, Guizhou Medical University, Guiyang, China
| | - Xiaoqin Zhu
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China.,School of Pharmacy, Guizhou Medical University, Guiyang, China
| | - Jie Pan
- Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China
| | - Yonglin Wang
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China
| | - Yanyu Lan
- Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China
| | - Yongjun Li
- Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China
| | - Aimin Wang
- Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China
| | - Jia Sun
- State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, China
| | - Chunhua Liu
- Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, China
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Wang L, Wu J, Chen J, Dou W, Zhao Q, Han J, Liu J, Su W, Li A, Liu P, An Z, Xu C, Sun Y. Advances in reconstructing intestinal functionalities in vitro: From two/three dimensional-cell culture platforms to human intestine-on-a-chip. Talanta 2021; 226:122097. [PMID: 33676654 DOI: 10.1016/j.talanta.2021.122097] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/02/2021] [Accepted: 01/05/2021] [Indexed: 12/20/2022]
Abstract
Standard two/three dimensional (2D/3D)-cell culture platforms have facilitated the understanding of the communications between various cell types and their microenvironments. However, they are still limited in recapitulating the complex functionalities in vivo, such as tissue formation, tissue-tissue interface, and mechanical/biochemical microenvironments of tissues and organs. Intestine-on-a-chip platforms offer a new way to mimic intestinal behaviors and functionalities by constructing in vitro intestinal models in microfluidic devices. This review summarizes the advances and limitations of the state-of-the-art 2D/3D-cell culture platforms, animal models, intestine chips, and the combined multi-organ chips related with intestines. Their applications to studying intestinal functions, drug testing, and disease modeling are introduced. Different intestinal cell sources are compared in terms of gene expression abilities and the recapitulated intestinal morphologies. Among these cells, cells isolated form human intestinal tissues and derived from pluripotent stem cells appear to be more suitable for in vitro reconstruction of intestinal organs. Key challenges of current intestine-on-a-chip platforms and future directions are also discussed.
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Affiliation(s)
- Li Wang
- Advanced Micro and Nano-instruments Center, School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China
| | - Jian Wu
- Advanced Micro and Nano-instruments Center, School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China
| | - Jun Chen
- Advanced Micro and Nano-instruments Center, School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China.
| | - Wenkun Dou
- Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Rd, Toronto, Ontario, M5S 3G8, Canada
| | - Qili Zhao
- Institute of Robotics and Automatic Information System (IRAIS) and the Tianjin Key Laboratory of Intelligent Robotic (tjKLIR), Nankai University, Tianjin, 300350, China
| | - Junlei Han
- Advanced Micro and Nano-instruments Center, School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China
| | - Jinliang Liu
- Advanced Micro and Nano-instruments Center, School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China
| | - Weiguang Su
- Advanced Micro and Nano-instruments Center, School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China
| | - Anqing Li
- Advanced Micro and Nano-instruments Center, School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China
| | - Pengbo Liu
- Advanced Micro and Nano-instruments Center, School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China
| | - Zhao An
- Changhai Hospital, Second Military Medical University, Shanghai, 200433, China
| | - Chonghai Xu
- Advanced Micro and Nano-instruments Center, School of Mechanical & Automotive Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China
| | - Yu Sun
- Department of Mechanical and Industrial Engineering, University of Toronto, 5 King's College Rd, Toronto, Ontario, M5S 3G8, Canada
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Raba G, Adamberg S, Adamberg K. Acidic pH enhances butyrate production from pectin by faecal microbiota. FEMS Microbiol Lett 2021; 368:6232156. [PMID: 33864456 DOI: 10.1093/femsle/fnab042] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Accepted: 04/15/2021] [Indexed: 12/17/2022] Open
Abstract
Environmental pH and gut transit rate are the key factors determining the dynamics of colonic microbiota. In this study, the effect of changing pH on the composition and metabolism of pooled faecal microbiota was elucidated at physiologically relevant dilution rates Dhigh = 0.2 and Dlow = 0.05 1/h. The results showed the best adaptability of Bacteroides ovatus within the pH range 6.0-8.0 at both dilution rates. The butyrate producing Faecalibacterium and Coprococcus comes were extremely sensitive to pH > 7.5, while the abundance of Akkermansia muciniphila increased significantly at pH >7 at Dhigh, causing a pH-dependant shift in the dynamics of mucin degrading species. Increased gas formation was observed at pH < 6.5. Substantially more CO2 was produced at Dlow than at Dhigh (18-29 vs 12-23 mmol per L medium, respectively). Methane was produced only at Dlow and pH > 7, consistent with the simultaneous increased abundance of Methanobrevibacter smithii. Our study confirmed the importance of pH in the development of faecal microbiota in pectin-supplemented medium. Fermentation of other dietary fibres can be studied using the same approach. The significance of pH should be more emphasized in gut research and diagnostics.
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Affiliation(s)
- Grete Raba
- Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn, Estonia
| | - Signe Adamberg
- Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn, Estonia
| | - Kaarel Adamberg
- Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn, Estonia.,Center of Food and Fermentation Technologies, Akadeemia tee 15A, Tallinn, Estonia
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Hanus M, Parada-Venegas D, Landskron G, Wielandt AM, Hurtado C, Alvarez K, Hermoso MA, López-Köstner F, De la Fuente M. Immune System, Microbiota, and Microbial Metabolites: The Unresolved Triad in Colorectal Cancer Microenvironment. Front Immunol 2021; 12:612826. [PMID: 33841394 PMCID: PMC8033001 DOI: 10.3389/fimmu.2021.612826] [Citation(s) in RCA: 112] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2020] [Accepted: 03/02/2021] [Indexed: 12/16/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide. As with other cancers, CRC is a multifactorial disease due to the combined effect of genetic and environmental factors. Most cases are sporadic, but a small proportion is hereditary, estimated at around 5-10%. In both, the tumor interacts with heterogeneous cell populations, such as endothelial, stromal, and immune cells, secreting different signals (cytokines, chemokines or growth factors) to generate a favorable tumor microenvironment for cancer cell invasion and metastasis. There is ample evidence that inflammatory processes have a role in carcinogenesis and tumor progression in CCR. Different profiles of cell activation of the tumor microenvironment can promote pro or anti-tumor pathways; hence they are studied as a key target for the control of cancer progression. Additionally, the intestinal mucosa is in close contact with a microorganism community, including bacteria, bacteriophages, viruses, archaea, and fungi composing the gut microbiota. Aberrant composition of this microbiota, together with alteration in the diet-derived microbial metabolites content (such as butyrate and polyamines) and environmental compounds has been related to CRC. Some bacteria, such as pks+ Escherichia coli or Fusobacterium nucleatum, are involved in colorectal carcinogenesis through different pathomechanisms including the induction of genetic mutations in epithelial cells and modulation of tumor microenvironment. Epithelial and immune cells from intestinal mucosa have Pattern-recognition receptors and G-protein coupled receptors (receptor of butyrate), suggesting that their activation can be regulated by intestinal microbiota and metabolites. In this review, we discuss how dynamics in the gut microbiota, their metabolites, and tumor microenvironment interplays in sporadic and hereditary CRC, modulating tumor progression.
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Affiliation(s)
- Michelle Hanus
- Laboratory of Innate Immunity, Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
| | - Daniela Parada-Venegas
- Laboratory of Innate Immunity, Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
| | - Glauben Landskron
- Laboratory of Innate Immunity, Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
| | | | - Claudia Hurtado
- Research Core, Academic Department, Clínica Las Condes, Santiago, Chile
| | - Karin Alvarez
- Cancer Center, Clínica Universidad de los Andes, Santiago, Chile
| | - Marcela A. Hermoso
- Laboratory of Innate Immunity, Program of Immunology, Faculty of Medicine, Institute of Biomedical Sciences, Universidad de Chile, Santiago, Chile
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47
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Eisele Y, Mallea PM, Gigic B, Stephens WZ, Warby CA, Buhrke K, Lin T, Boehm J, Schrotz-King P, Hardikar S, Huang LC, Pickron TB, Scaife CL, Viskochil R, Koelsch T, Peoples AR, Pletneva MA, Bronner M, Schneider M, Ulrich AB, Swanson EA, Toriola AT, Shibata D, Li CI, Siegel EM, Figueiredo J, Janssen KP, Hauner H, Round J, Ulrich CM, Holowatyj AN, Ose J. Fusobacterium nucleatum and Clinicopathologic Features of Colorectal Cancer: Results From the ColoCare Study. Clin Colorectal Cancer 2021; 20:e165-e172. [PMID: 33935016 DOI: 10.1016/j.clcc.2021.02.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 02/08/2021] [Accepted: 02/24/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Fusobacterium nucleatum (Fn), a bacterium associated with a wide spectrum of infections, has emerged as a key microbe in colorectal carcinogenesis. However, the underlying mechanisms and clinical relevance of Fn in colorectal cancer (CRC) remain incompletely understood. PATIENTS AND METHODS We examined associations between Fn abundance and clinicopathologic characteristics among 105 treatment-naïve CRC patients enrolled in the international, prospective ColoCare Study. Electronic medical charts, including pathological reports, were reviewed to document clinicopathologic features. Quantitative real-time polymerase chain reaction (PCR) was used to amplify/detect Fn DNA in preoperative fecal samples. Multinomial logistic regression was used to analyze associations between Fn abundance and patient sex, age, tumor stage, grade, site, microsatellite instability, body mass index (BMI), alcohol consumption, and smoking history. Cox proportional hazards models were used to investigate associations of Fn abundance with overall survival in adjusted models. RESULTS Compared to patients with undetectable or low Fn abundance, patients with high Fn abundance (n = 22) were 3-fold more likely to be diagnosed with rectal versus colon cancer (odds ratio [OR] = 3.01; 95% confidence interval [CI], 1.06-8.57; P = .04) after adjustment for patient sex, age, BMI, and study site. Patients with high Fn abundance also had a 5-fold increased risk of being diagnosed with rectal cancer versus right-sided colon cancer (OR = 5.32; 95% CI, 1.23-22.98; P = .03). There was no statistically significant association between Fn abundance and overall survival. CONCLUSION Our findings suggest that Fn abundance in fecal samples collected prior to surgery varies by tumor site among treatment-naïve CRC patients. Overall, fecal Fn abundance may have diagnostic and prognostic significance in the clinical management of CRC.
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Affiliation(s)
- Yannick Eisele
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT; Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Patrick M Mallea
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT
| | - Biljana Gigic
- Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany
| | - W Zac Stephens
- Department of Pathology, University of Utah, Salt Lake City, UT
| | - Christy A Warby
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT
| | - Kate Buhrke
- Department of Pathology, University of Utah, Salt Lake City, UT
| | - Tengda Lin
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT
| | - Juergen Boehm
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT
| | - Petra Schrotz-King
- Division of Preventive Oncology, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany
| | - Sheetal Hardikar
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT
| | - Lyen C Huang
- Division of General Surgery, Department of Surgery, School of Medicine, University of Utah, Salt Lake City, UT
| | - T Bartley Pickron
- Division of General Surgery, Department of Surgery, School of Medicine, University of Utah, Salt Lake City, UT
| | - Courtney L Scaife
- Division of General Surgery, Department of Surgery, School of Medicine, University of Utah, Salt Lake City, UT
| | - Richard Viskochil
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT
| | - Torsten Koelsch
- Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany
| | - Anita R Peoples
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT
| | - Maria A Pletneva
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Pathology, University of Utah, Salt Lake City, UT
| | - Mary Bronner
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Pathology, University of Utah, Salt Lake City, UT
| | - Martin Schneider
- Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany
| | - Alexis B Ulrich
- Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany
| | - Eric A Swanson
- Department of Pathology, University of Utah, Salt Lake City, UT
| | | | - David Shibata
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN
| | - Christopher I Li
- Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA
| | - Erin M Siegel
- Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
| | - Jane Figueiredo
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA
| | - Klaus-Peter Janssen
- Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany
| | - Hans Hauner
- Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; Else Kröner-Fresenius-Centre for Nutritional Medicine, School of Life Sciences, Technical University of Munich, Munich, Germany
| | - June Round
- Department of Pathology, University of Utah, Salt Lake City, UT
| | - Cornelia M Ulrich
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT
| | - Andreana N Holowatyj
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN; Vanderbilt-Ingram Cancer Center, Nashville, TN.
| | - Jennifer Ose
- Huntsman Cancer Institute, Salt Lake City, UT; Department of Population Health Sciences, University of Utah, Salt Lake City, UT.
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Kanazawa A, Aida M, Yoshida Y, Kaga H, Katahira T, Suzuki L, Tamaki S, Sato J, Goto H, Azuma K, Shimizu T, Takahashi T, Yamashiro Y, Watada H. Effects of Synbiotic Supplementation on Chronic Inflammation and the Gut Microbiota in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study. Nutrients 2021; 13:nu13020558. [PMID: 33567701 PMCID: PMC7914668 DOI: 10.3390/nu13020558] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2020] [Revised: 01/27/2021] [Accepted: 02/04/2021] [Indexed: 12/23/2022] Open
Abstract
The aim of this study was to investigate the effects of 24-week synbiotic supplementation on chronic inflammation and the gut microbiota in obese patients with type 2 diabetes. We randomized 88 obese patients with type 2 diabetes to one of two groups for 24 weeks: control or synbiotic (Lacticaseibacillus paracasei strain Shirota (previously Lactobacillus casei strain Shirota) and Bifidobacterium breve strain Yakult, and galactooligosaccharides). The primary endpoint was the change in interleukin-6 from baseline to 24 weeks. Secondary endpoints were evaluation of the gut microbiota in feces and blood, fecal organic acids, high-sensitivity C-reactive protein, lipopolysaccharide-binding protein, and glycemic control. Synbiotic administration for 24 weeks did not significantly affect changes in interleukin-6 from baseline to 24 weeks (0.35 ± 1.99 vs. −0.24 ± 1.75 pg/mL, respectively). Relative to baseline, however, at 24 weeks after synbiotic administration there were positive changes in the counts of Bifidobacterium and total lactobacilli, the relative abundances of Bifidobacterium species such as Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and the concentrations of acetic and butyric acids in feces. No significant changes in inflammatory markers were found in the synbiotic group compared to the control group. However, synbiotic administration at least partially improved the gut environment in obese patients with type 2 diabetes.
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Affiliation(s)
- Akio Kanazawa
- Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (H.K.); (T.K.); (L.S.); (S.T.); (J.S.); (H.G.); (K.A.); (T.S.); (H.W.)
- Correspondence: ; Tel.: +81-3-5802-1579
| | - Masanori Aida
- Food Research Department, Yakult Central Institute, Tokyo 186-8650, Japan; (M.A.); (Y.Y.)
| | - Yasuto Yoshida
- Food Research Department, Yakult Central Institute, Tokyo 186-8650, Japan; (M.A.); (Y.Y.)
| | - Hideyoshi Kaga
- Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (H.K.); (T.K.); (L.S.); (S.T.); (J.S.); (H.G.); (K.A.); (T.S.); (H.W.)
| | - Takehiro Katahira
- Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (H.K.); (T.K.); (L.S.); (S.T.); (J.S.); (H.G.); (K.A.); (T.S.); (H.W.)
| | - Luka Suzuki
- Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (H.K.); (T.K.); (L.S.); (S.T.); (J.S.); (H.G.); (K.A.); (T.S.); (H.W.)
| | - Shoko Tamaki
- Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (H.K.); (T.K.); (L.S.); (S.T.); (J.S.); (H.G.); (K.A.); (T.S.); (H.W.)
| | - Junko Sato
- Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (H.K.); (T.K.); (L.S.); (S.T.); (J.S.); (H.G.); (K.A.); (T.S.); (H.W.)
| | - Hiromasa Goto
- Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (H.K.); (T.K.); (L.S.); (S.T.); (J.S.); (H.G.); (K.A.); (T.S.); (H.W.)
| | - Kosuke Azuma
- Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (H.K.); (T.K.); (L.S.); (S.T.); (J.S.); (H.G.); (K.A.); (T.S.); (H.W.)
| | - Tomoaki Shimizu
- Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (H.K.); (T.K.); (L.S.); (S.T.); (J.S.); (H.G.); (K.A.); (T.S.); (H.W.)
| | - Takuya Takahashi
- Yakult Honsha European Research Center for Microbiology, 9052 Gent-Zwijnaarde, Belgium;
| | - Yuichiro Yamashiro
- Probiotics Research Laboratory, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan;
| | - Hirotaka Watada
- Department of Metabolism & Endocrinology, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan; (H.K.); (T.K.); (L.S.); (S.T.); (J.S.); (H.G.); (K.A.); (T.S.); (H.W.)
- Center for Therapeutic Innovations in Diabetes, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
- Center for Identification of Diabetic Therapeutic Targets, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
- Sportology Center, Graduate School of Medicine, Juntendo University, Tokyo 113-8421, Japan
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Verediano TA, Viana ML, das G.V. Tostes M, Costa NM. The Potential Prebiotic Effects of Yacon (Smallanthus sonchifolius) in Colorectal Cancer. CURRENT NUTRITION & FOOD SCIENCE 2021. [DOI: 10.2174/1573401316999200605160433] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Background:
Colorectal cancer is caused by genetic predisposition and lifestyle risk factors
and is associated with altered homeostasis of the intestinal microbiota. Evidence suggests that
chronic infection and inflammation contribute to carcinogenic mutagenesis and promote cancer initiation
and progression. Food components with prebiotic properties, such as fructooligosaccharides
(FOS), promote intestinal integrity and health benefits. Yacon (Smallanthus sonchifolius) is an abundant
source of FOS, which are fermented by beneficial bacteria, improving the intestinal environment
affected by colorectal cancer.
Objective:
In the current review, the aim was to discuss colorectal cancer and its inflammatory process
of development. Also, some general aspects concerning yacon roots and its prebiotic properties
are described. Finely, the beneficial effects of yacon to reduce intestinal parameters altered due to
colorectal cancer are summarized.
Conclusion:
It was verified that yacon might improve immunological parameters, intestinal barrier,
intestinal microbiota, and inflammation in induced colorectal cancer in animals, especially. Researches
with humans must be further investigated to prove these positive effects.
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Affiliation(s)
- Thaísa A. Verediano
- Department of Pharmacy and Nutrition, Center for Exact Natural and Health Sciences, Federal University of Espirito Santo, Alegre-ES, Brazil
| | - Mirelle L. Viana
- Department of Pharmacy and Nutrition, Center for Exact Natural And Health Sciences, Federal University of Espirito Santo, Alegre-ES, Brazil
| | - Maria das G.V. Tostes
- Department of Pharmacy and Nutrition, Center for Exact Natural And Health Sciences, Federal University of Espirito Santo, Alegre-ES, Brazil
| | - Neuza M.B. Costa
- Department of Pharmacy and Nutrition, Center for Exact Natural And Health Sciences, Federal University of Espirito Santo, Alegre-ES, Brazil
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Abstract
The use of fecal inoculums for in vitro fermentation models requires a viable gut microbiota, capable of fermenting the unabsorbed nutrients. Fresh samples from human donors are used; however, the availability of fresh fecal inoculum and its inherent variability is often a problem. This study aimed to optimize a method of preserving pooled human fecal samples for in vitro fermentation studies. Different conditions and times of storage at −20 °C were tested. In vitro fermentation experiments were carried out for both fresh and frozen inoculums, and the metabolic profile compared. In comparison with the fresh, the inoculum frozen in a PBS and 30% glycerol solution, had a significantly lower (p < 0.05) bacterial count (<1 log CFU/mL). However, no significant differences (p < 0.05) were found between the metabolic profiles after 48 h. Hence, a PBS and 30% glycerol solution can be used to maintain the gut microbiota viability during storage at −20 °C for at least 3 months, without interfering with the normal course of colonic fermentation.
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