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1
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Nascimento da Silva K, Fávero AG, Ribeiro W, Ferreira CM, Sartorelli P, Cardili L, Bogsan CS, Bertaglia Pereira JN, de Cássia Sinigaglia R, Cristina de Moraes Malinverni A, Ribeiro Paiotti AP, Miszputen SJ, Ambrogini-Júnior O. Effects of kefir fermented milk beverage on sodium dextran sulfate (DSS)-induced colitis in rats. Heliyon 2022; 9:e12707. [PMID: 36685418 PMCID: PMC9852935 DOI: 10.1016/j.heliyon.2022.e12707] [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: 07/08/2022] [Revised: 11/14/2022] [Accepted: 12/22/2022] [Indexed: 12/29/2022] Open
Abstract
Background and aim The etiopathogenesis of inflammatory bowel disease (IBD) is associated with different factors such as genetic, infectious, immunological, and environmental, including modification of the gut microbiota. IBD's conventional pharmacological therapeutic approaches have become a challenge due to side effects, complications from prolonged use, and higher costs. Kefir fermented milk beverage is a functional food that has demonstrated multiple beneficial effects including anti-inflammatory and antioxidant activity. Alternative therapeutic strategies have been used for IBD as more natural products with low-cost and easy acquisition. The aim of this study is to evaluate the anti-inflammatory effects of kefir fermented milk beverage on sodium dextran sulfate (DSS)-induced colitis in rats. Methods We used 4 groups to perform this study: baseline control (BC), kefir control (KC), 5% untreated DSS-induced colitis (DSS), and 5% DSS-induced colitis treated with kefir (DSSK). The animals received fermented kefir milk beverage ad libitum for six days and the disease activity index was recorded daily. Colon samples were processed for Transmission Electron Microscopy and histopathological evaluation. We analyzed short fatty chain acids through the fecal sample using gas chromatography. Results Kefir supplementation was able to reduce the clinical activity index and inflammatory process evidenced by decreased neutrophil accumulation, decreased reticulum edema, and increased autophagosomes. Also, showed a trend to increase the levels of acetate and propionate. Conclusions Our results suggest that kefir fermented milk beverage may have an anti-inflammatory effect minimizing the intestinal damage of DSS-induced colitis.
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Affiliation(s)
- Karina Nascimento da Silva
- Division of Gastroenterology, Universidade Federal de São Paulo – Escola Paulista de Medicina, UNIFESP, SP, Brazil
| | - Aline Garnevi Fávero
- Division of Gastroenterology, Universidade Federal de São Paulo – Escola Paulista de Medicina, UNIFESP, SP, Brazil
| | - William Ribeiro
- Institute of Environmental, Chemistry and Pharmaceutical Sciences, Department of Pharmaceutics Sciences - Universidade Federal de São Paulo, Diadema, SP, Brazil
| | - Caroline Marcantonio Ferreira
- Institute of Environmental, Chemistry and Pharmaceutical Sciences, Department of Pharmaceutics Sciences - Universidade Federal de São Paulo, Diadema, SP, Brazil
| | - Patrícia Sartorelli
- Institute of Environmental, Chemistry and Pharmaceutical Sciences, Department of Pharmaceutics Sciences - Universidade Federal de São Paulo, Diadema, SP, Brazil
| | - Leonardo Cardili
- Laboratory of Experimental and Molecular Pathology, Department of Pathology - Universidade Federal de São Paulo, São Paulo, SP, Brazil
| | - Cristina Stewart Bogsan
- Laboratory of Fermented Foods of the Faculty of Pharmaceutical Sciences – University of São Paulo
| | | | | | | | - Ana Paula Ribeiro Paiotti
- Division of Gastroenterology, Universidade Federal de São Paulo – Escola Paulista de Medicina, UNIFESP, SP, Brazil,Corresponding author.
| | - Sender Jankiel Miszputen
- Division of Gastroenterology, Universidade Federal de São Paulo – Escola Paulista de Medicina, UNIFESP, SP, Brazil
| | - Orlando Ambrogini-Júnior
- Division of Gastroenterology, Universidade Federal de São Paulo – Escola Paulista de Medicina, UNIFESP, SP, Brazil
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2
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Zheng L, Duan SL, Dai YC, Wu SC. Role of adherent invasive Escherichia coli in pathogenesis of inflammatory bowel disease. World J Clin Cases 2022; 10:11671-11689. [PMID: 36405271 PMCID: PMC9669839 DOI: 10.12998/wjcc.v10.i32.11671] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 09/04/2022] [Accepted: 10/11/2022] [Indexed: 02/05/2023] Open
Abstract
Gut microbiota imbalances play an important role in inflammatory bowel disease (IBD), but no single pathogenic microorganism critical to IBD that is specific to the IBD terminal ileum mucosa or can invade intestinal epithelial cells has been found. Invasive Escherichia coli (E. coli) adhesion to macrophages is considered to be closely related to the pathogenesis of inflammatory bowel disease. Further study of the specific biological characteristics of adherent invasive E. coli (AIEC) may contribute to a further understanding of IBD pathogenesis. This review explores the relationship between AIEC and the intestinal immune system, discusses the prevalence and relevance of AIEC in Crohn's disease and ulcerative colitis patients, and describes the relationship between AIEC and the disease site, activity, and postoperative recurrence. Finally, we highlight potential therapeutic strategies to attenuate AIEC colonization in the intestinal mucosa, including the use of phage therapy, antibiotics, and anti-adhesion molecules. These strategies may open up new avenues for the prevention and treatment of IBD in the future.
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Affiliation(s)
- Lie Zheng
- Department of Gastroenterology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an 322000, Shaanxi Province, China
| | - Sheng-Lei Duan
- Department of Gastroenterology, Shaanxi Provincial Hospital of Traditional Chinese Medicine, Xi’an 322000, Shaanxi Province, China
| | - Yan-Cheng Dai
- Department of Gastroenterology, Shanghai Traditional Chinese Medicine Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Shi-Cheng Wu
- Department of Proctology, Gansu Academy of Traditional Chinese Medicine, Gansu Hospital of Traditional Chinese Medicine, Lanzhou 730050, Gansu Province, China
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3
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Huang Y, Lin X, Yu S, Chen R, Chen W. Intestinal Engineered Probiotics as Living Therapeutics: Chassis Selection, Colonization Enhancement, Gene Circuit Design, and Biocontainment. ACS Synth Biol 2022; 11:3134-3153. [PMID: 36094344 DOI: 10.1021/acssynbio.2c00314] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Intestinal probiotics are often used for the in situ treatment of diseases, such as metabolic disorders, tumors, and chronic inflammatory infections. Recently, there has been an increased emphasis on intelligent, customized treatments with a focus on long-term efficacy; however, traditional probiotic therapy has not kept up with this trend. The use of synthetic biology to construct gut-engineered probiotics as live therapeutics is a promising avenue in the treatment of specific diseases, such as phenylketonuria and inflammatory bowel disease. These studies generally involve a series of fundamental design issues: choosing an engineered chassis, improving the colonization ability of engineered probiotics, designing functional gene circuits, and ensuring the safety of engineered probiotics. In this review, we summarize the relevant past research, the progress of current research, and discuss the key issues that restrict the widespread application of intestinal engineered probiotic living therapeutics.
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Affiliation(s)
- Yan Huang
- Team SZU-China at iGEM 2021, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China
| | - Xiaojun Lin
- Team SZU-China at iGEM 2021, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China
| | - Siyang Yu
- Team SZU-China at iGEM 2021, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China
| | - Ruiyue Chen
- Team SZU-China at iGEM 2021, Institute for Advanced Study, Shenzhen University, Shenzhen 518060, China
| | - Weizhao Chen
- Team SZU-China at iGEM 2021, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, China.,Shenzhen Key Laboratory for Microbial Gene Engineering, Shenzhen University, Shenzhen 518060, China
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Comparative Genomics and Pan-Genome Driven Prediction of a Reduced Genome of Akkermansia muciniphila. Microorganisms 2022; 10:microorganisms10071350. [PMID: 35889069 PMCID: PMC9315967 DOI: 10.3390/microorganisms10071350] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Revised: 06/25/2022] [Accepted: 07/02/2022] [Indexed: 02/01/2023] Open
Abstract
Akkermanisia muciniphila imparts important health benefits and is considered a next-generation probiotic. It is imperative to understand the genomic diversity and metabolic potential of the species for safer applications as probiotics. As it resides with both health-promoting and pathogenic bacteria, understanding the evolutionary patterns are crucial, but this area remains largely unexplored. Moreover, pan-genome has previously been established based on only a limited number of strains and without careful strain selection. The pan-genomics have become very important for understanding species diversity and evolution. In the current study, a systematic approach was used to find a refined pan-genome profile of A. muciniphila by excluding too-diverse strains based on average nucleotide identity-based species demarcation. The strains were divided into four phylogroups using a variety of clustering techniques. Horizontal gene transfer and recombination patterns were also elucidated. Evolutionary patterns revealed that different phylogroups were expanding differently. Furthermore, a comparative evaluation of the metabolic potential of the pan-genome and its subsections was performed. Lastly, the study combines functional annotation, persistent genome, and essential genes to devise an approach to determine a minimal genome that can systematically remove unwanted genes, including virulent factors. The selection of one strain to be used as a chassis for the prediction of a reduced genome was very carefully performed by analyzing several genomic parameters, including the number of unique genes and the resistance and pathogenic potential of the strains. The strategy could be applied to other microbes, including human-associated microbiota, towards a common goal of predicting a minimal or a reduced genome.
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5
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Li M, Yang L, Zhao L, Bai F, Liu X. Comparison of Intestinal Microbes in Noninfectious Anterior Scleritis Patients With and Without Rheumatoid Arthritis. Front Microbiol 2022; 13:925929. [PMID: 35756002 PMCID: PMC9218904 DOI: 10.3389/fmicb.2022.925929] [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: 04/22/2022] [Accepted: 05/23/2022] [Indexed: 11/16/2022] Open
Abstract
We compared intestinal microbes in anterior noninfectious scleritis patients with and without rheumatoid arthritis. Active noninfectious anterior scleritis patients without other immune diseases (G group, 16 patients) or with active rheumatoid arthritis (GY group, seven patients) were included in this study. Eight age- and sex-matched healthy subjects served as controls (N group). DNA was extracted from fecal samples. The V3-V4 16S rDNA region was amplified and sequenced by high-throughput 16S rDNA analysis, and microbial contents were determined. A significant decrease in species richness in the GY group was revealed by α- and β-diversity analyses (p = 0.02 and p = 0.004, respectively). At the genus level, 14 enriched and 10 decreased microbes in the G group and 13 enriched and 18 decreased microbes in the GY group were identified. Among them, four microbes were enriched in both the G and GY groups, including Turicibacter, Romboutsia, Atopobium, and Coprobacillus. Although two microbes (Lachnospiraceae_ND3007_group and Eggerthella) exhibited similar tendencies in the G and GY groups, changes in these microbes were more significant in the GY group (p < 0.05). Interaction analysis showed that Intestinibacter, Romboutsia, and Turicibacter, which were enriched in both the G and GY groups, correlated positively with each other. In addition, nine microbes were decreased in the GY group, which demonstrates a potential protective role for these microbes in the pathogenesis of scleritis via interactions with each other.
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Affiliation(s)
- Mengyao Li
- Ophthalmologic Center of the Second Hospital, Jilin University, Changchun, China
| | - Li Yang
- Ophthalmologic Center of the Second Hospital, Jilin University, Changchun, China
| | - Liangliang Zhao
- Ophthalmologic Center of the Second Hospital, Jilin University, Changchun, China
| | - Feng Bai
- Ophthalmologic Center of the Second Hospital, Jilin University, Changchun, China
| | - Xiaoli Liu
- Ophthalmologic Center of the Second Hospital, Jilin University, Changchun, China
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6
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Xu L, Yang CS, Liu Y, Zhang X. Effective Regulation of Gut Microbiota With Probiotics and Prebiotics May Prevent or Alleviate COVID-19 Through the Gut-Lung Axis. Front Pharmacol 2022; 13:895193. [PMID: 35548347 PMCID: PMC9081431 DOI: 10.3389/fphar.2022.895193] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Accepted: 03/31/2022] [Indexed: 12/14/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) can disrupt the gut microbiota balance, and patients usually have intestinal disorders. The intestine is the largest immune organ of the human body, and gut microbes can affect the immune function of the lungs through the gut-lung axis. Many lines of evidence support the role of beneficial bacteria in enhancing human immunity, preventing pathogen colonization, and thereby reducing the incidence and severity of infection. In this article, we review the possible approach of modulating microbiota to help prevent and treat respiratory tract infections, including COVID-19, and discuss the possibility of using probiotics and prebiotics for this purpose. We also discuss the mechanism by which intestinal micro-flora regulate immunity and the effects of probiotics on the intestinal micro-ecological balance. Based on this understanding, we propose the use of probiotics and prebiotics to modulate gut microbiota for the prevention or alleviation of COVID-19 through the gut-lung axis.
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Affiliation(s)
- Lei Xu
- Department of Food Science and Engineering, Ningbo University, Ningbo, China
| | - Chung S. Yang
- Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers The State University of New Jersey, Piscataway, NJ, United States
- *Correspondence: Chung S. Yang, ; Xin Zhang,
| | - Yanan Liu
- Department of Food Science and Engineering, Ningbo University, Ningbo, China
| | - Xin Zhang
- Department of Food Science and Engineering, Ningbo University, Ningbo, China
- *Correspondence: Chung S. Yang, ; Xin Zhang,
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7
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Dibo M, Ventimiglia MS, Valeff N, Serradell MDLÁ, Jensen F. An overview of the role of probiotics in pregnancy-associated pathologies with a special focus on preterm birth. J Reprod Immunol 2022; 150:103493. [DOI: 10.1016/j.jri.2022.103493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Revised: 01/20/2022] [Accepted: 02/08/2022] [Indexed: 10/19/2022]
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8
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Design and in situ biosynthesis of precision therapies against gastrointestinal pathogens. CURRENT OPINION IN PHYSIOLOGY 2021. [DOI: 10.1016/j.cophys.2021.06.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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9
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Dey G, Mookherjee S. Probiotics-targeting new milestones from gut health to mental health. FEMS Microbiol Lett 2021; 368:6332281. [PMID: 34329424 DOI: 10.1093/femsle/fnab096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 07/28/2021] [Indexed: 12/15/2022] Open
Abstract
Conventional probiotic food research was primarily focused on their benefits for gut health. Recently with the confirmation that the gut microbiota has a bidirectional connection with the brain, it is being proposed that modification of the microbiota can possibly extirpate neurological diseases. Development of probiotic foods and formulations for neural health benefits has garnered interest, with a renewed focus. In this context, this review discusses the evidences collected on the anxiolytic and antidepressant effects of probiotics, especially during the time span of 2015-till now. Although, more clinical trials are necessary to elucidate the exact mechanism of probiotic mode of action but several of the established probiotic strains have been investigated and it appears that few of them have demonstrated their potential as 'psychobiotics'. The formulation of new psychobiotic-based therapeutics is in the spotlight. It is expected that in near future, biological effect of probiotics on neurological conditions will open up an entirely new avenue for personalized medication and healthcare in mental health, and they can be tailored according to the gut-microbiota of specific individuals.
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Affiliation(s)
- Gargi Dey
- School of Biotechnology, Campus 11, Kalinga Institute of Industrial Technology, Deemed to be University, Patia, Bhubaneswar, Odisha. PIN-751024, India
| | - Sohom Mookherjee
- School of Biotechnology, Campus 11, Kalinga Institute of Industrial Technology, Deemed to be University, Patia, Bhubaneswar, Odisha. PIN-751024, India.,Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT 84112, USA
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10
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Curciarello R, Canziani KE, Salto I, Barbiera Romero E, Rocca A, Doldan I, Peton E, Brayer S, Sambuelli AM, Goncalves S, Tirado P, Correa GJ, Yantorno M, Garbi L, Docena GH, Serradell MDLÁ, Muglia CI. Probiotic Lactobacilli Isolated from Kefir Promote Down-Regulation of Inflammatory Lamina Propria T Cells from Patients with Active IBD. Front Pharmacol 2021; 12:658026. [PMID: 33935778 PMCID: PMC8082687 DOI: 10.3389/fphar.2021.658026] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 03/04/2021] [Indexed: 01/17/2023] Open
Abstract
Ulcerative colitis and Crohn’s disease, the two main forms of inflammatory bowel disease (IBD), are immunologically mediated disorders. Several therapies are focused on activated T cells as key targets. Although Lactobacillus kefiri has shown anti-inflammatory effects in animal models, few studies were done using human mucosal T cells. The aim of this work was to investigate the immunomodulatory effects of this bacterium on intestinal T cells from patients with active IBD. Mucosal biopsies and surgical samples from IBD adult patients (n = 19) or healthy donors (HC; n = 5) were used. Lamina propria mononuclear cells were isolated by enzymatic tissue digestion, and entero-adhesive Escherichia coli-specific lamina propria T cells (LPTC) were expanded. The immunomodulatory properties of L. kefiri CIDCA 8348 strain were evaluated on biopsies and on anti-CD3/CD28-activated LPTC. Secreted cytokines were quantified by ELISA, and cell proliferation and viability were assessed by flow cytometry. We found that L. kefiri reduced spontaneous release of IL-6 and IL-8 from inflamed biopsies ex vivo. Activated LPTC from IBD patients showed low proliferative rates and reduced secretion of TNF-α, IL-6, IFN-γ and IL-13 in the presence of L. kefiri. In addition, L. kefiri induced an increased frequency of CD4+FOXP3+ LPTC along with high levels of IL-10. This is the first report showing an immunomodulatory effect of L. kefiri CIDCA 8348 on human intestinal cells from IBD patients. Understanding the mechanisms of interaction between probiotics and immune mucosal cells may open new avenues for treatment and prevention of IBD.
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Affiliation(s)
- Renata Curciarello
- Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Asociado CIC PBA, La Plata, Argentina
| | - Karina E Canziani
- Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Asociado CIC PBA, La Plata, Argentina
| | - Ileana Salto
- Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Asociado CIC PBA, La Plata, Argentina
| | - Emanuel Barbiera Romero
- Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Asociado CIC PBA, La Plata, Argentina
| | - Andrés Rocca
- Unidad Endoscopía, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Ciudad Autónoma de Buenos Aires, Argentina
| | - Ivan Doldan
- Unidad Endoscopía, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Ciudad Autónoma de Buenos Aires, Argentina
| | - Emmanuel Peton
- Unidad de Proctología, Departamento de Cirugía, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Ciudad Autónoma de Buenos Aires, Argentina
| | - Santiago Brayer
- Unidad de Proctología, Departamento de Cirugía, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Ciudad Autónoma de Buenos Aires, Argentina
| | - Alicia M Sambuelli
- Sección de Enfermedades Inflamatorias Del Intestino, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Ciudad Autónoma de Buenos Aires, Argentina
| | - Silvina Goncalves
- Sección de Enfermedades Inflamatorias Del Intestino, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Ciudad Autónoma de Buenos Aires, Argentina
| | - Pablo Tirado
- Sección de Enfermedades Inflamatorias Del Intestino, Hospital de Gastroenterología Dr. Carlos Bonorino Udaondo, Ciudad Autónoma de Buenos Aires, Argentina
| | - Gustavo J Correa
- Área de Enfermedad Inflamatoria Intestinal, Sala de Endoscopía, Servicio de Gastroenterología, Hospital Interzonal General de Agudos General San Martín, La Plata, Argentina
| | - Martín Yantorno
- Área de Enfermedad Inflamatoria Intestinal, Sala de Endoscopía, Servicio de Gastroenterología, Hospital Interzonal General de Agudos General San Martín, La Plata, Argentina
| | - Laura Garbi
- Área de Enfermedad Inflamatoria Intestinal, Sala de Endoscopía, Servicio de Gastroenterología, Hospital Interzonal General de Agudos General San Martín, La Plata, Argentina
| | - Guillermo H Docena
- Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Asociado CIC PBA, La Plata, Argentina
| | - María de Los Ángeles Serradell
- Cátedra de Microbiología, Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, La Plata, Argentina
| | - Cecilia I Muglia
- Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), CONICET-Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Asociado CIC PBA, La Plata, Argentina
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Singh TP, Natraj BH. Next-generation probiotics: a promising approach towards designing personalized medicine. Crit Rev Microbiol 2021; 47:479-498. [PMID: 33822669 DOI: 10.1080/1040841x.2021.1902940] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Second brain, forgotten organ, individual's identity card, and host's fingerprint are the few collective terms that are often used to describe the gut microbiome because of its variability, accountability, and its role in deciding the host's health. Also, the understanding of this host health-gut microbiota relationship can create an opportunity to control an individual's health by manipulating the gut microbiota composition. Several approaches like administration of probiotic, prebiotics, synbiotics, faecal microbiota transplantation have been tried to mitigate the dysbiosis originated ill effects. But the effects of these approaches are highly generic and non-specific. This creates the necessity to design personalized medicine that focuses on treatment of specific disease considering the individual specific gut microbiome. The health promoting commensals could be the new promising prophylactic and therapeutic agents for designing personalized medicine. These commensals are designated as next-generation probiotics (NGPs) and their unusual characteristics, unknown identity and special growth requirements have presented difficulties for researcher, industrial exploitation, and regulatory agencies. In this perspective, this review discusses the concept of NGPs, NGP candidates as tool for designing personalized medicine, designer probiotics as NGPs, required regulatory framework, and propose a road map to develop the NGP based product.
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Affiliation(s)
- Tejinder Pal Singh
- Dairy Microbiology Department, College of Dairy Science and Technology, Lala Lajpat Rai University of Veterinary and Animal Science, Hisar, India
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12
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Zhou Z, Chen X, Sheng H, Shen X, Sun X, Yan Y, Wang J, Yuan Q. Engineering probiotics as living diagnostics and therapeutics for improving human health. Microb Cell Fact 2020; 19:56. [PMID: 32131831 PMCID: PMC7055047 DOI: 10.1186/s12934-020-01318-z] [Citation(s) in RCA: 74] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 02/26/2020] [Indexed: 02/08/2023] Open
Abstract
The gut microbiota that inhabit our gastrointestinal tract are well known to play an important role in maintaining human health in many aspects, including facilitating the digestion and absorption of nutrients, protecting against pathogens and regulating immune system. Gut microbiota dysbiosis is associated with a lot of diseases, such as inflammatory bowel disease, allergy, obesity, cardiovascular and neurodegenerative diseases and cancers. With the increasing knowledge of the microbiome, utilization of probiotic bacteria in modulating gut microbiota to prevent and treat a large number of disorders and diseases has gained much interest. In recent years, aided by the continuous development of tools and techniques, engineering probiotic microbes with desired characteristics and functionalities to benefit human health has made significant progress. In this paper, we summarize the recent advances in design and construction of probiotics as living diagnostics and therapeutics for probing and treating a series of diseases including metabolic disorders, inflammation and pathogenic bacteria infections. We also discuss the current challenges and future perspectives in expanding the application of probiotics for disease treatment and detection. We intend to provide insights and ideas for engineering of probiotics to better serve disease therapy and human health.
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Affiliation(s)
- Zhao Zhou
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 15# Beisanhuan East Road, Chaoyang District, Beijing, 100029, China
| | - Xin Chen
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 15# Beisanhuan East Road, Chaoyang District, Beijing, 100029, China
| | - Huakang Sheng
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 15# Beisanhuan East Road, Chaoyang District, Beijing, 100029, China
| | - Xiaolin Shen
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 15# Beisanhuan East Road, Chaoyang District, Beijing, 100029, China
| | - Xinxiao Sun
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 15# Beisanhuan East Road, Chaoyang District, Beijing, 100029, China
| | - Yajun Yan
- College of Engineering, The University of Georgia, Athens, GA, 30602, USA
| | - Jia Wang
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 15# Beisanhuan East Road, Chaoyang District, Beijing, 100029, China.
| | - Qipeng Yuan
- State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, 15# Beisanhuan East Road, Chaoyang District, Beijing, 100029, China.
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13
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Engineered Lactococcus lactis Secreting IL-23 Receptor-Targeted REX Protein Blockers for Modulation of IL-23/Th17-Mediated Inflammation. Microorganisms 2019; 7:microorganisms7050152. [PMID: 31137908 PMCID: PMC6560508 DOI: 10.3390/microorganisms7050152] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2019] [Revised: 05/09/2019] [Accepted: 05/23/2019] [Indexed: 12/13/2022] Open
Abstract
Lactococcus lactis, a probiotic bacterium of food origin, has recently been demonstrated as a suitable strain for the production and in vivo delivery of therapeutically important proteins into the gut. We aimed to engineer recombinant L. lactis cells producing/secreting REX binding proteins that have been described as IL-23 receptor (IL-23R) blockers and IL-23R antagonists suppressing the secretion of cytokine IL-17A, a pivotal step in the T-helper Th17-mediated pro-inflammatory cascade, as well as in the development of autoimmune diseases, including inflammatory bowel disease (IBD). To reach this goal, we introduced cDNA sequences coding for REX009, REX115, and REX125 proteins into plasmid vectors carrying a Usp45 secretion signal, a FLAG tag sequence consensus, and a LysM-containing cA surface anchor (AcmA), thus allowing cell-surface peptidoglycan anchoring. These plasmids, or their non-FLAG/non-AcmA versions, were introduced into L. lactis host cells, thus generating unique recombinant L. lactis-REX strains. We demonstrate that all three REX proteins are expressed in L. lactis cells and are efficiently displayed on the bacterial surface, as tested by flow cytometry using an anti-FLAG antibody conjugate. Upon 10-fold concentration of the conditioned media, a REX125 secretory variant can be detected by Western blotting. To confirm that the FLAG/non-FLAG REX proteins displayed by L. lactis retain their binding specificity, cell-surface interactions of REX proteins with an IL-23R-IgG chimera were demonstrated by flow cytometry. In addition, statistically significant binding of secreted REX009 and REX115 proteins to bacterially produced, soluble human IL-23R was confirmed by ELISA. We conclude that REX-secreting L. lactis strains were engineered that might serve as IL-23/IL-23R blockers in an experimentally induced mouse model of colitis.
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