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1
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Kadam O, Dalai S, Chauhan B, Guru RR, Mitra S, Raytekar N, Kumar R. Nanobiotechnology Unveils the Power of Probiotics: A Comprehensive Review on the Synergistic Role of Probiotics and Advanced Nanotechnology in Enhancing Geriatric Health. Cureus 2025; 17:e80478. [PMID: 40225478 PMCID: PMC11990693 DOI: 10.7759/cureus.80478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/12/2025] [Indexed: 04/15/2025] Open
Abstract
The geriatric population, comprising ages 65 and above, encounters distinct health obstacles because of physiological changes and heightened vulnerability to diseases. New technologies are being investigated to tackle the intricate health requirements of this population. Recent advancements in probiotics and nanotechnology offer promising strategies to enhance geriatric health by improving nutrient absorption, modulating gut microbiota, and delivering targeted therapeutic agents. Probiotics play a crucial role in maintaining gut homeostasis, reducing inflammation, and supporting metabolic functions. However, challenges such as limited viability and efficacy in harsh gastrointestinal conditions hinder their therapeutic potential. Advanced nanotechnology can overcome these constraints by enhancing the efficacy of probiotics through nano-encapsulation, controlled delivery, and improvement of bioavailability. This review explores the synergistic potential of probiotics and advanced nanotechnology in addressing age-related health concerns. It highlights key developments in probiotic formulations, nano-based delivery systems, and their combined impact on gut health, immunity, and neuroprotection. The convergence of probiotics and nanotechnology represents a novel and transformative approach to promoting healthy aging, paving the way for innovative therapeutic interventions.
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Affiliation(s)
- Onkar Kadam
- Biotechnology, Symbiosis Centre for Nanoscience and Nanotechnology, Symbiosis International (Deemed) University, Pune, IND
| | - Swayamprava Dalai
- Biotechnology, Symbiosis Centre for Nanoscience and Nanotechnology, Symbiosis International (Deemed) University, Pune, IND
| | - Bhawna Chauhan
- School of Biotech Engineering and Food Technology, Chandigarh University, Chandigarh, IND
| | - Rashmi Ranjan Guru
- Hospital Administration, All India Institute of Medical Sciences, Jodhpur, Jodhpur, IND
- Hospital Administration, Postgraduate Institute of Medical Education and Research, Chandigarh, Chandigarh, IND
| | - Subhodip Mitra
- Hospital Administration, All India Institute of Medical Sciences, Kalyani, Kolkata, IND
| | - Namita Raytekar
- Medical Technology, Symbiosis Institute of Health Sciences, Pune, IND
| | - Rahul Kumar
- Hospital Administration, Symbiosis University Hospital & Research Centre, Pune, IND
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2
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Zhu L, Yang X. Gut Microecological Prescription: A Novel Approach to Regulating Intestinal Micro-Ecological Balance. Int J Gen Med 2025; 18:603-626. [PMID: 39931312 PMCID: PMC11807788 DOI: 10.2147/ijgm.s504616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Accepted: 01/21/2025] [Indexed: 02/13/2025] Open
Abstract
The intestinal microecology is comprises intestinal microorganisms and other components constituting the entire ecosystem, presenting characteristics of stability and dynamic balance. Current research reveals intestinal microecological imbalances are related to various diseases. However, fundamental research and clinical applications have not been effectively integrated. Considering the importance and complexity of regulating the intestinal microecological balance, this study provides an overview of the high-risk factors affecting intestinal microecology and detection methods. Moreover, it proposes the definition of intestinal microecological imbalance and the definition, formulation, and outcomes of gut microecological prescription to facilitate its application in clinical practice, thus promoting clinical research on intestinal microecology and improving the quality of life of the population.
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Affiliation(s)
- Lingping Zhu
- The Affiliated Nanhua Hospital, Department of General Practice, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China
- School of Public Health, Fudan University, Shanghai, 200433, People’s Republic of China
| | - Xuefeng Yang
- The Affiliated Nanhua Hospital, Department of General Practice, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People’s Republic of China
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3
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Al-Matouq J, Al-Ghafli H, Alibrahim NN, Alsaffar N, Radwan Z, Ali MD. Unveiling the Interplay Between the Human Microbiome and Gastric Cancer: A Review of the Complex Relationships and Therapeutic Avenues. Cancers (Basel) 2025; 17:226. [PMID: 39858007 PMCID: PMC11763844 DOI: 10.3390/cancers17020226] [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: 11/25/2024] [Revised: 12/23/2024] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
The human microbiota plays a crucial role in maintaining overall health and well-being. The gut microbiota has been implicated in developing and progressing various diseases, including cancer. This review highlights the related mechanisms and the compositions that influence cancer pathogenesis with a highlight on gastric cancer. We provide a comprehensive overview of the mechanisms by which the microbiome influences cancer development, progression, and response to treatment, with a focus on identifying potential biomarkers for early detection, prevention strategies, and novel therapeutic interventions that leverage microbiome modulation. This comprehensive review can guide future research and clinical practices in understanding and harnessing the microbiome to optimize gastric cancer therapies.
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Affiliation(s)
- Jenan Al-Matouq
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Hawra Al-Ghafli
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Noura N. Alibrahim
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Nida Alsaffar
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Zaheda Radwan
- Department of Medical Laboratory Sciences, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia; (H.A.-G.); (N.N.A.); (N.A.); (Z.R.)
| | - Mohammad Daud Ali
- Department of Pharmacy, Mohammed Al-Mana College for Medical Sciences, Al Safa, Dammam 34222, Saudi Arabia;
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Shi M, Fan H, Liu H, Zhang Y. Effects of saponins R b1 and R e in American ginseng intervention on intestinal microbiota of aging model. Front Nutr 2024; 11:1435778. [PMID: 39346650 PMCID: PMC11428427 DOI: 10.3389/fnut.2024.1435778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2024] [Accepted: 08/27/2024] [Indexed: 10/01/2024] Open
Abstract
Aging brings about physiological dysfunction, disease, and eventual mortality. An increasing number of studies indicate that aging can easily lead to dysbiosis of the gut microbiota, which can further affect digestion, nerves, cognition, emotions, and more. Therefore, gut bacteria play an important role in regulating the physical functions of aging populations. While saponins, the primary components of American ginseng, are frequently utilized for treating common ailments in the elderly due to their potent antioxidant properties, there is a scarcity of comprehensive studies on aging organisms. This study focused on 18 month old aging mice and investigated the effects of single intervention and combined intervention of Rb1 and Re, the main components of Panax quinquefolium saponins, on the gut microbiota of aging mice. High throughput 16s RNA gene sequencing analysis was performed on the gut contents of the tested mice, and the results showed that Rb1 and Re had a significant impact on the gut microbiota. Rb1, Re, and Rb1 + Re can effectively enhance the diversity of gut microbiota, especially in the combined Rb1 + Re group, which can recover to the level of young mice. Re can promote the abundance of probiotics such as Lactobacillus, Lactobacillaceae, and Lactobacillus, and inhibit the abundance of harmful bacteria such as Enterobacteriaceae. This indicates that the intervention of Rb1, Re, and Rb1 + Re can maintain the homeostasis of gut microbiota, and the combined application of Rb1 + Re has a better effect. The relationship between aging, brain gut axis, and gut microbiota is very close. Saponins can improve the gut microbiota of aging individuals by maintaining the balance of gut microbiota and the normal function of the brain gut axis, enabling the body to achieve a gut microbiota homeostasis closer to that of young healthy mice.
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Affiliation(s)
- Mao Shi
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
- Jilin Provincial Center for Disease Control and Prevention, Changchun, China
| | - HongXiu Fan
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
| | - HongCheng Liu
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
| | - YanRong Zhang
- College of Food Science and Engineering, Jilin Agricultural University, Changchun, China
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Weaver L, Troester A, Jahansouz C. The Impact of Surgical Bowel Preparation on the Microbiome in Colon and Rectal Surgery. Antibiotics (Basel) 2024; 13:580. [PMID: 39061262 PMCID: PMC11273680 DOI: 10.3390/antibiotics13070580] [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: 05/15/2024] [Revised: 06/13/2024] [Accepted: 06/21/2024] [Indexed: 07/28/2024] Open
Abstract
Preoperative bowel preparation, through iterations over time, has evolved with the goal of optimizing surgical outcomes after colon and rectal surgery. Although bowel preparation is commonplace in current practice, its precise mechanism of action, particularly its effect on the human gut microbiome, has yet to be fully elucidated. Absent intervention, the gut microbiota is largely stable, yet reacts to dietary influences, tissue injury, and microbiota-specific byproducts of metabolism. The routine use of oral antibiotics and mechanical bowel preparation prior to intestinal surgical procedures may have detrimental effects previously thought to be negligible. Recent evidence highlights the sensitivity of gut microbiota to antibiotics, bowel preparation, and surgery; however, there is a lack of knowledge regarding specific causal pathways that could lead to therapeutic interventions. As our understanding of the complex interactions between the human host and gut microbiota grows, we can explore the role of bowel preparation in specific microbiome alterations to refine perioperative care and improve outcomes. In this review, we outline the current fund of information regarding the impact of surgical bowel preparation and its components on the adult gut microbiome. We also emphasize key questions pertinent to future microbiome research and their implications for patients undergoing colorectal surgery.
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Affiliation(s)
- Lauren Weaver
- Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA; (L.W.); (A.T.)
| | - Alexander Troester
- Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA; (L.W.); (A.T.)
| | - Cyrus Jahansouz
- Division of Colon & Rectal Surgery, Department of Surgery, University of Minnesota, 420 Delaware St. SE, MMC 450, Minneapolis, MN 55455, USA
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Chen HZ, Zeng YY, Cai GX, Gu WD, Yang Y. Differential analysis of serum immunology and gut microbiota in patients with gastrointestinal diseases. Front Microbiol 2024; 15:1323842. [PMID: 38751718 PMCID: PMC11094713 DOI: 10.3389/fmicb.2024.1323842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 04/05/2024] [Indexed: 05/18/2024] Open
Abstract
Objective Gastric and intestinal diseases possess distinct characteristics although they are interconnected. The primary objective of this study was to investigate the pathogenesis of gastrointestinal diseases through different analyses of clinical characteristics, serum immunology, and gut microbiota in patients with gastrointestinal diseases. Methods We collected serum samples from 89 patients with gastrointestinal diseases and 9 healthy controls for immunological assessment, stool samples for DNA extraction, library construction, sequencing, as well as clinical data for subsequent analysis. Results Regarding clinical characteristics, there were significant differences between the disease group and the healthy control (HC) group, particularly in terms of age, cancer antigen 125 (CA125), cancer antigen 199 (CA199), alpha-fetoprotein (AFP), total bilirubin (TBIL) and indirect bilirubin (IBIL). The intestinal disease (ID) group exhibited the highest IL-6 level, which significantly differed from the stomach disease (SD) group (p < 0.05). In comparing the HC with the ID groups, significant differences in abundance were detected across 46 species. The HC group displayed a greater abundance of Clostridiales, Clostridia, Firmicutes, Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, Actinobacteria, Veillonellaceae, Longum, Copri, Megamonas and Callidus than other species. Similarly, when comparing the HC with the SD groups, significant differences in abundance were identified among 49 species, with only one species that the Lachnospiraceae in the HC group exhibited a higher abundance than others. Furthermore, certain clinical characteristics, such as CA125, CA199, glucose (Glu), creatine kinase-MB (CKMB) and interleukin-22 (IL-22), displayed positive correlations with enriched gut species in the ID and SD groups, while exhibiting a negative correlation with the HC group. Conclusion The disturbance in human gut microbiota is intimately associated with the development and progression of gastrointestinal diseases. Moreover, the gut microbiota in the HC group was found more diverse than that in the ID and SD groups, and there were significant differences in microbial species among the three groups at different classification levels. Notably, a correlation was identified between specific clinical characteristics (e.g., CA125, CA199, Glu, CKMB and IL-22) and gut microbiota among patients with gastrointestinal diseases.
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Affiliation(s)
- Huan Zhu Chen
- Biochemistry Teaching and Research Office of the Basic Department of the Medical College of Jiaying University, Meizhou, China
| | - Yu Yang Zeng
- Biochemistry Teaching and Research Office of the Basic Department of the Medical College of Jiaying University, Meizhou, China
| | - Guo Xiong Cai
- Laboratory Department of the Affiliated Hospital of the Medical College of Jiaying University, Meizhou, China
| | - Wei Dan Gu
- Laboratory Department of the Affiliated Hospital of the Medical College of Jiaying University, Meizhou, China
| | - YaLi Yang
- Biochemistry Teaching and Research Office of the Basic Department of the Medical College of Jiaying University, Meizhou, China
- Guangdong Provincial Key Laboratory of Conservation and Precision Utilization of Characteristic Agricultural Resources in Mountainous Areas, Meizhou, China
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7
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Apalowo OE, Adegoye GA, Obuotor TM. Microbial-Based Bioactive Compounds to Alleviate Inflammation in Obesity. Curr Issues Mol Biol 2024; 46:1810-1831. [PMID: 38534735 DOI: 10.3390/cimb46030119] [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: 02/07/2024] [Revised: 02/20/2024] [Accepted: 02/23/2024] [Indexed: 03/28/2024] Open
Abstract
The increased prevalence of obesity with several other metabolic disorders, including diabetes and non-alcoholic fatty liver disease, has reached global pandemic proportions. Lifestyle changes may result in a persistent positive energy balance, hastening the onset of these age-related disorders and consequently leading to a diminished lifespan. Although suggestions have been raised on the possible link between obesity and the gut microbiota, progress has been hampered due to the extensive diversity and complexities of the gut microbiota. Being recognized as a potential biomarker owing to its pivotal role in metabolic activities, the dysregulation of the gut microbiota can give rise to a persistent low-grade inflammatory state associated with chronic diseases during aging. This chronic inflammatory state, also known as inflammaging, induced by the chronic activation of the innate immune system via the macrophage, is controlled by the gut microbiota, which links nutrition, metabolism, and the innate immune response. Here, we present the functional roles of prebiotics, probiotics, synbiotics, and postbiotics as bioactive compounds by underscoring their putative contributions to (1) the reduction in gut hyperpermeability due to lipopolysaccharide (LPS) inactivation, (2) increased intestinal barrier function as a consequence of the upregulation of tight junction proteins, and (3) inhibition of proinflammatory pathways, overall leading to the alleviation of chronic inflammation in the management of obesity.
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Affiliation(s)
- Oladayo Emmanuel Apalowo
- Department of Food Science, Nutrition and Health Promotion, Mississippi State University, Starkville, MS 39762, USA
| | - Grace Adeola Adegoye
- Department of Nutrition and Health Science, Ball State University, Muncie, IN 47306, USA
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Li R, Roy R. Gut Microbiota and Its Role in Anti-aging Phenomenon: Evidence-Based Review. Appl Biochem Biotechnol 2023; 195:6809-6823. [PMID: 36930406 DOI: 10.1007/s12010-023-04423-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/07/2023] [Indexed: 03/18/2023]
Abstract
The gut microbiota widely varies from individual to individual, but the variation shows stability over a period of time. The presence of abundant bacterial taxa is a common structure that determines the microbiota of human being. The presence of this microbiota greatly varies from geographic location, sex, food habits and age. Microbiota existing within the gut plays a significant role in nutrient absorption, development of immunity, curing of diseases and various developmental phases. With change in age, chronology diversification and variation of gut microbiota are observed within human being. But it has been observed that with the enhancement of age the richness of the microbial diversity has shown a sharp decline. The enhancement of age also results in the drift of the characteristic of the microbes associated with the microbiota from commensals to pathogenic. Various studies have shown that age associated gut-dysbiosis may result in decrease in tlongevity along with unhealthy aging. The host signalling pathways regulate the presence of the gut microbiota and their longevity. The presence of various nutrients regulates the presence of various microbial species. Innate immunity can be triggered due to the mechanism of gut dysbiosis resulting in the development of various age-related pathological syndromes and early aging. The gut microbiota possesses the ability to communicate with the host system with the help of various types of biomolecules, epigenetic mechanisms and various types of signalling-independent pathways. Drift in this mechanism of communication may affect the life span along with the health of the host. Thus, this review would focus on the use of gut-microbiota in anti-aging and healthy conditions of the host system.
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Affiliation(s)
- Ruishan Li
- Guiyang Healthcare Vocational University, Guiyang, China.
| | - Rupak Roy
- SHRM Biotechnologies Pvt. Ltd, Kolkata, India
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Colletti A, Pellizzato M, Cicero AF. The Possible Role of Probiotic Supplementation in Inflammation: A Narrative Review. Microorganisms 2023; 11:2160. [PMID: 37764004 PMCID: PMC10535592 DOI: 10.3390/microorganisms11092160] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/01/2023] [Accepted: 08/17/2023] [Indexed: 09/29/2023] Open
Abstract
The fine balance between symbiotic and potentially opportunistic and/or pathogenic microorganisms can undergo quantitative alterations, which, when associated with low intestinal biodiversity, could be responsible for the development of gut inflammation and the so-called "intestinal dysbiosis". This condition is characterized by the disbalance of a fine synergistic mechanism involving the mucosal barrier, the intestinal neuroendocrine system, and the immune system that results in an acute inflammatory response induced by different causes, including viral or bacterial infections of the digestive tract. More frequently, however, dysbiosis is induced slowly and subtly by subliminal causal factors, resulting in a chronic condition related to different diseases affecting the digestive tract and other organs and apparatuses. Studies on animal models, together with studies on humans, highlight the significant role of the gut microbiota and microbiome in the occurrence of inflammatory conditions such as metabolic syndrome and cardiovascular diseases (CVDs); neurodegenerative, urologic, skin, liver, and kidney pathologies; and premature aging. The blood translocation of bacterial fragments has been found to be one of the processes linked to gut dysbiosis and responsible for the possible occurrence of "metabolic endotoxemia" and systemic inflammation, associated with an increased risk of oxidative stress and related diseases. In this context, supplementation with different probiotic strains has been shown to restore gut eubiosis, especially if administered in long-term treatments. The aim of this review is to describe the anti-inflammatory effects of specific probiotic strains observed in clinical trials and the respective indications, highlighting the differences in efficacy depending on strain, formulation, time and duration of treatment, and dosage used.
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Affiliation(s)
- Alessandro Colletti
- Department of Science and Drug Technology, University of Turin, 10124 Turin, Italy
- Italian Society of Nutraceutical Formulators (SIFNut), 31033 Treviso, Italy
| | - Marzia Pellizzato
- Italian Society of Nutraceutical Formulators (SIFNut), 31033 Treviso, Italy
| | - Arrigo Francesco Cicero
- Medical and Surgical Sciences Department, University of Bologna, 40126 Bologna, Italy;
- IRCCS AOUBO, 40138 Bologna, Italy
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10
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Roselló-Añón A, Chiappe C, Valverde-Vázquez MR, Sangüesa-Nebot MJ, Gómez-Cabrera MC, Pérez-Martínez G, Doménech-Fernández J. [Translated article] Pilot study to determine the association between gut microbiota and fragility hip fracture. Rev Esp Cir Ortop Traumatol (Engl Ed) 2023; 67:T279-T289. [PMID: 36878282 DOI: 10.1016/j.recot.2023.03.002] [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: 12/20/2022] [Accepted: 01/07/2023] [Indexed: 03/07/2023] Open
Abstract
INTRODUCTION Hip fractures are the most common cause of hospital admission to orthopaedic departments in Europe and they generate a major health problem. Therefore, it is of great interest to identify additional risk factors that will help us to better understand the pathophysiology of these fractures and improve our preventive capacity. There is sufficient data to support the theory of modulation of bone mass by gut microbiota (osteomicrobiology); however, there is a lack of human clinical studies directly linking microbiota to hip fracture risk. MATERIAL AND METHODS Observational, analytical, case-control study. The sample consisted of 50 patients and it was distributed as follows: 25 elderly patients with fragility hip fracture and 25 subjects without fracture. The intestinal microbiota was determined by DNA extraction from stool samples and 16S ribosomal DNA sequencing after generation of gene libraries. RESULTS Alpha diversity revealed an elevation of the estimators for the taxonomic class level in the hip fracture group. The orders Bacteroidales, Oscillospirales, Lachnospirales, Peptostreptococcales-Tissierellales and Enterobacterales were the dominant orders in both groups. In patients with fracture, a significant percentage increase in the orders Bacteroidales (p<.001) and Peptostreptococcales-Tissierellales (p<.005) was observed, as well as a decrease in the orders Lachnospirales (p<.001) compared to controls. CONCLUSIONS This study has found an association between a specific microbiota in elderly patients with fragility hip fracture. These findings open the door to new strategies to prevent hip fractures. Modification of the microbiota through probiotics may prove to be an effective method to reduce the risk of hip fracture.
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Affiliation(s)
- A Roselló-Añón
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Arnau de Vilanova, Valencia, Spain.
| | - C Chiappe
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Arnau de Vilanova, Valencia, Spain
| | - M R Valverde-Vázquez
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Arnau de Vilanova, Valencia, Spain
| | - M J Sangüesa-Nebot
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Arnau de Vilanova, Valencia, Spain
| | - M C Gómez-Cabrera
- Departamento de Fisiología, Facultad de Medicina, Universidad de Valencia, CIBERFES, Fundación Investigación Hospital Clínico Universitario/INCLIVA, Valencia, Spain
| | - G Pérez-Martínez
- Laboratory of Lactic acid Bacteria and Probiotics, Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (CSIC), Valencia, Spain
| | - J Doménech-Fernández
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Arnau de Vilanova, Valencia, Spain; Universidad Católica de Valencia, Valencia, Spain
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11
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Roselló-Añón A, Chiappe C, Valverde-Vázquez MR, Sangüesa-Nebot MJ, Gómez-Cabrera MC, Pérez-Martínez G, Doménech-Fernández J. Pilot study to determine the association between gut microbiota and fragility hip fracture. Rev Esp Cir Ortop Traumatol (Engl Ed) 2023; 67:279-289. [PMID: 36642372 DOI: 10.1016/j.recot.2023.01.002] [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: 12/20/2022] [Revised: 01/02/2023] [Accepted: 01/07/2023] [Indexed: 01/14/2023] Open
Abstract
INTRODUCTION Hip fractures are the most common cause of hospital admission to orthopaedic departments in Europe and they generate a major health problem. Therefore, it is of great interest to identify additional risk factors that will help us to better understand the pathophysiology of these fractures and improve our preventive capacity. There is sufficient data to support the theory of modulation of bone mass by gut microbiota (osteomicrobiology); however, there is a lack of human clinical studies directly linking microbiota to hip fracture risk. MATERIAL AND METHODS Observational, analytical, case-control study. The sample consisted of 50 patients and it was distributed as follows: 25 elderly patients with fragility hip fracture and 25 subjects without fracture. The intestinal microbiota was determined by DNA extraction from stool samples and 16S ribosomal DNA sequencing after generation of gene libraries. RESULTS Alpha diversity revealed an elevation of the estimators for the taxonomic class level in the hip fracture group. The orders Bacteroidales, Oscillospirales, Lachnospirales, Peptostreptococcales-Tissierellales and Enterobacterales were the dominant orders in both groups. In patients with fracture, a significant percentage increase in the orders Bacteroidales (p<.001) and Peptostreptococcales-Tissierellales (p<.005) was observed, as well as a decrease in the orders Lachnospirales (p<.001) compared to controls. CONCLUSIONS This study has found an association between a specific microbiota in elderly patients with fragility hip fracture. These findings open the door to new strategies to prevent hip fractures. Modification of the microbiota through probiotics may prove to be an effective method to reduce the risk of hip fracture.
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Affiliation(s)
- A Roselló-Añón
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Arnau de Vilanova, Valencia, España.
| | - C Chiappe
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Arnau de Vilanova, Valencia, España
| | - M R Valverde-Vázquez
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Arnau de Vilanova, Valencia, España
| | - M J Sangüesa-Nebot
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Arnau de Vilanova, Valencia, España
| | - M C Gómez-Cabrera
- Departamento de Fisiología, Facultad de Medicina, Universidad de Valencia, CIBERFES, Fundación Investigación Hospital Clínico Universitario/INCLIVA, Valencia, España
| | - G Pérez-Martínez
- Laboratory of Lactic acid bacteria and Probiotics, Department of Food Biotechnology, Instituto de Agroquímica y Tecnología de Alimentos, Consejo Superior de Investigaciones Científicas (CSIC), Valencia, España
| | - J Doménech-Fernández
- Servicio de Cirugía Ortopédica y Traumatología, Hospital Arnau de Vilanova, Valencia, España; Universidad Católica de Valencia, Valencia, España
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12
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Banaszak M, Górna I, Woźniak D, Przysławski J, Drzymała-Czyż S. Association between Gut Dysbiosis and the Occurrence of SIBO, LIBO, SIFO and IMO. Microorganisms 2023; 11:573. [PMID: 36985147 PMCID: PMC10052891 DOI: 10.3390/microorganisms11030573] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 02/21/2023] [Accepted: 02/22/2023] [Indexed: 03/03/2023] Open
Abstract
Gut microbiota is the aggregate of all microorganisms in the human digestive system. There are 1014 CFU/mL of such microorganisms in the human body, including bacteria, viruses, fungi, archaea and protozoa. The Firmicutes and Bacteroidetes bacteria phyla comprise 90% of the human gut microbiota. The microbiota support the healthy functioning of the human body by helping with digestion (mainly via short-chain fatty acids and amino acids) and producing short-chain fatty acids. In addition, it exhibits many physiological functions, such as forming the intestinal epithelium, intestinal integrity maintenance, the production of vitamins, and protection against pathogens. An altered composition or the number of microorganisms, known as dysbiosis, disrupts the body's homeostasis and can lead to the development of inflammatory bowel disease, irritable bowel syndrome, and metabolic diseases such as diabetes, obesity and allergies. Several types of disruptions to the gut microbiota have been identified: SIBO (Small Intestinal Bacterial Overgrowth), LIBO (Large Intestinal Bacterial Overgrowth), SIFO (Small Intestinal Fungal Overgrowth), and IMO (Intestinal Methanogen Overgrowth). General gastrointestinal problems such as abdominal pain, bloating, gas, diarrhoea and constipation are the main symptoms of dysbiosis. They lead to malabsorption, nutrient deficiencies, anaemia and hypoproteinaemia. Increased lipopolysaccharide (LPS) permeability, stimulating the inflammatory response and resulting in chronic inflammation, has been identified as the leading cause of microbial overgrowth in the gut. The subject literature is extensive but of limited quality. Despite the recent interest in the gut microbiome and its disorders, more clinical research is needed to determine the pathophysiology, effective treatments, and prevention of small and large intestinal microbiota overgrowth. This review was designed to provide an overview of the available literature on intestinal microbial dysbiosis (SIBO, LIBO, SIFO and IMO) and to determine whether it represents a real threat to human health.
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Affiliation(s)
- Michalina Banaszak
- Department of Bromatology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
- Poznan University of Medical Sciences Doctoral School, Poznan University of Medical Sciences, Bukowska 70, 60-812 Poznan, Poland
| | - Ilona Górna
- Department of Bromatology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Dagmara Woźniak
- Department of Bromatology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
- Poznan University of Medical Sciences Doctoral School, Poznan University of Medical Sciences, Bukowska 70, 60-812 Poznan, Poland
| | - Juliusz Przysławski
- Department of Bromatology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
| | - Sławomira Drzymała-Czyż
- Department of Bromatology, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland
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13
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Beer and Microbiota: Pathways for a Positive and Healthy Interaction. Nutrients 2023; 15:nu15040844. [PMID: 36839202 PMCID: PMC9966200 DOI: 10.3390/nu15040844] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/02/2023] [Accepted: 02/04/2023] [Indexed: 02/10/2023] Open
Abstract
Beer is one of the most consumed drinks worldwide. It contains numerous categories of antioxidants, phenolic products, traces of group B vitamins, minerals (selenium, silicon, potassium), soluble fibers and microorganisms. Low or moderate beer consumption, with or without alcohol, showed positive effects on health by stimulating the development of a healthy microbiota. In the present review we focused on four components responsible with interaction with gut microbiota: microorganisms, polyphenols, fiber and melanoidins, their presence in usual beers and on perspectives of development of fortified beers with enhanced effects on gut microbiota. Though microorganisms rarely escape pasteurization of beer, there are new unpasteurized types that might bring strains with probiotic effects. The polyphenols from beer are active on the gut microbiota stimulating its development, with consequent local anti-inflammatory and antioxidant effects. Their degradation products have prebiotic action and may combat intestinal dysbiosis. Beer contains dietary fiber such as non-starchy, non-digestible carbohydrates (β-glucans, arabinoxylans, mannose, fructose polymers, etc.) that relate with gut microbiota through fermentation, serving as a nutrient substrate. Another type of substances that are often considered close to fiber because they have an extremely low digestibility, melanoidins (melanosaccharides), give beer antioxidant and antibacterial properties. Though there are not many research studies in this area, the conclusion of this review is that beer seems a good candidate for a future functional food and that there are many pathways by which its ingredients can influence in a positive manner the human gut microbiota. Of course, there are many technological hinderances to overcome. However, designing functional beers fortified with fiber, antioxidants and probiotics, with a very low or no alcoholic content, will counteract the negative perception of beer consumption, will nullify the negative effects of alcohol, while simultaneously exerting a positive action on the gut microbiota.
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Choi Y, Choi SI, Kim N, Nam RH, Jang JY, Na HY, Shin CM, Lee DH, Min H, Kim YR, Seok YJ. Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids. Dig Dis Sci 2023; 68:2427-2440. [PMID: 36670324 DOI: 10.1007/s10620-023-07835-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2022] [Accepted: 01/09/2023] [Indexed: 01/22/2023]
Abstract
BACKGROUND/AIMS A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex. METHODS Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured. RESULTS HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation. CONCLUSIONS The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference.
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Affiliation(s)
- Yonghoon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Soo In Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea. .,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
| | - Ryoung Hee Nam
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Jae Young Jang
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Hee Young Na
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Huitae Min
- Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, South Korea
| | - Yeon-Ran Kim
- Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, South Korea
| | - Yeong-Jae Seok
- Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul, South Korea
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15
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Aggarwal N, Kitano S, Puah GRY, Kittelmann S, Hwang IY, Chang MW. Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies. Chem Rev 2023; 123:31-72. [PMID: 36317983 PMCID: PMC9837825 DOI: 10.1021/acs.chemrev.2c00431] [Citation(s) in RCA: 118] [Impact Index Per Article: 59.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Indexed: 01/12/2023]
Abstract
The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering.
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Affiliation(s)
- Nikhil Aggarwal
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
| | - Shohei Kitano
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
| | - Ginette Ru Ying Puah
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
- Wilmar-NUS
(WIL@NUS) Corporate Laboratory, National
University of Singapore, Singapore 117599, Singapore
- Wilmar
International Limited, Singapore 138568, Singapore
| | - Sandra Kittelmann
- Wilmar-NUS
(WIL@NUS) Corporate Laboratory, National
University of Singapore, Singapore 117599, Singapore
- Wilmar
International Limited, Singapore 138568, Singapore
| | - In Young Hwang
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
- Department
of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
- Singapore
Institute of Technology, Singapore 138683, Singapore
| | - Matthew Wook Chang
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
- Wilmar-NUS
(WIL@NUS) Corporate Laboratory, National
University of Singapore, Singapore 117599, Singapore
- Department
of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
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16
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Mozota M, Castro I, Gómez-Torres N, Arroyo R, Gutiérrez-Díaz I, Delgado S, Rodríguez JM, Alba C. Administration of Ligilactobacillus salivarius CECT 30632 to elderly during the COVID-19 pandemic: Nasal and fecal metataxonomic analysis and fatty acid profiling. Front Microbiol 2022; 13:1052675. [PMID: 36590434 PMCID: PMC9800801 DOI: 10.3389/fmicb.2022.1052675] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 11/30/2022] [Indexed: 12/23/2022] Open
Abstract
Elderly was the most affected population during the first COVID-19 and those living in nursing homes represented the most vulnerable group, with high mortality rates, until vaccines became available. In a previous article, we presented an open-label trial showing the beneficial effect of the strain Ligilactobacillus salivarius CECT 30632 (previously known as L. salivarius MP101) on the functional and nutritional status, and on the nasal and fecal inflammatory profiles of elderly residing in a nursing home highly affected by the pandemic. The objective of this post-hoc analysis was to elucidate if there were changes in the nasal and fecal bacteriomes of a subset of these patients as a result of the administration of the strain for 4 months and, also, its impact on their fecal fatty acids profiles. Culture-based methods showed that, while L. salivarius (species level) could not be detected in any of the fecal samples at day 0, L. salivarius CECT 30632 (strain level) was present in all the recruited people at day 120. Paradoxically, the increase in the L. salivarius counts was not reflected in changes in the metataxonomic analysis of the nasal and fecal samples or in changes in the fatty acid profiles in the fecal samples of the recruited people. Overall, our results indicate that L. salivarius CECT 30632 colonized, at least temporarily, the intestinal tract of the recruited elderly and may have contributed to improvements in their functional, nutritional, and immunological status, without changing the general structure of their nasal and fecal bacteriomes when assessed at the genus level. They also suggest the ability of low abundance bacteria to train immunity.
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Affiliation(s)
- Marta Mozota
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
| | - Irma Castro
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
| | - Natalia Gómez-Torres
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
| | - Rebeca Arroyo
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
| | - Isabel Gutiérrez-Díaz
- Department of Microbiology and Biochemistry, Dairy Research Institute of Asturias (IPLA-CSIC), Villaviciosa, Spain
| | - Susana Delgado
- Department of Microbiology and Biochemistry, Dairy Research Institute of Asturias (IPLA-CSIC), Villaviciosa, Spain
| | - Juan Miguel Rodríguez
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
| | - Claudio Alba
- Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
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17
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Hurvitz N, Elkhateeb N, Sigawi T, Rinsky-Halivni L, Ilan Y. Improving the effectiveness of anti-aging modalities by using the constrained disorder principle-based management algorithms. FRONTIERS IN AGING 2022; 3:1044038. [PMID: 36589143 PMCID: PMC9795077 DOI: 10.3389/fragi.2022.1044038] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 11/22/2022] [Indexed: 12/15/2022]
Abstract
Aging is a complex biological process with multifactorial nature underlined by genetic, environmental, and social factors. In the present paper, we review several mechanisms of aging and the pre-clinically and clinically studied anti-aging therapies. Variability characterizes biological processes from the genome to cellular organelles, biochemical processes, and whole organs' function. Aging is associated with alterations in the degrees of variability and complexity of systems. The constrained disorder principle defines living organisms based on their inherent disorder within arbitrary boundaries and defines aging as having a lower variability or moving outside the boundaries of variability. We focus on associations between variability and hallmarks of aging and discuss the roles of disorder and variability of systems in the pathogenesis of aging. The paper presents the concept of implementing the constrained disease principle-based second-generation artificial intelligence systems for improving anti-aging modalities. The platform uses constrained noise to enhance systems' efficiency and slow the aging process. Described is the potential use of second-generation artificial intelligence systems in patients with chronic disease and its implications for the aged population.
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Affiliation(s)
- Noa Hurvitz
- Faculty of Medicine, Hebrew University and Department of Medicine, Hadassah Medical Center, Jerusalem, Israel
| | - Narmine Elkhateeb
- Faculty of Medicine, Hebrew University and Department of Medicine, Hadassah Medical Center, Jerusalem, Israel
| | - Tal Sigawi
- Faculty of Medicine, Hebrew University and Department of Medicine, Hadassah Medical Center, Jerusalem, Israel
| | - Lilah Rinsky-Halivni
- Braun School of Public Health, Hebrew University of Jerusalem, Jerusalem, Israel,Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Yaron Ilan
- Faculty of Medicine, Hebrew University and Department of Medicine, Hadassah Medical Center, Jerusalem, Israel,*Correspondence: Yaron Ilan,
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18
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Ye J, Wu Z, Zhao Y, Zhang S, Liu W, Su Y. Role of gut microbiota in the pathogenesis and treatment of diabetes mullites: Advanced research-based review. Front Microbiol 2022; 13:1029890. [PMID: 36338058 PMCID: PMC9627042 DOI: 10.3389/fmicb.2022.1029890] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 09/26/2022] [Indexed: 02/05/2023] Open
Abstract
Gut microbiota plays an important role in the proper functioning of human organisms, while its dysbiosis is associated with disease in various body organs. Diabetes mellitus (DM) is a set of heterogeneous metabolic diseases characterized by hyperglycemia caused by direct or indirect insulin deficiency. There is growing evidence that gut microbiota dysbiosis is closely linked to the development of DM. Gut microbiota composition changes in type 1 diabetes mullites (T1DM) and type 2 diabetes mullites (T2DM) patients, which may cause gut leakiness and uncontrolled entry of antigens into the circulation system, triggering an immune response that damages the isle β cells or metabolic disorders. This review summarizes gut microbiota composition in healthy individuals and compares it to diabetes mullites patients. The possible pathogenesis by which gut microbiota dysbiosis causes DM, particularly gut leakiness and changes in gut microbiota metabolites is also discussed. It also presents the process of microbial-based therapies of DM.
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Affiliation(s)
- Junjun Ye
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- Shantou University Medical College, Shantou, China
| | - Zezhen Wu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Yifei Zhao
- School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Shuo Zhang
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Shantou University Medical College, Shantou, China
- The First Affiliated Hospital of Shantou University Medical College, Shantou, China
| | - Weiting Liu
- School of Nursing, Anhui University of Chinese Medicine, Hefei, Anhui, China
| | - Yu Su
- Center of Teaching Evaluation and Faculty Development, Anhui University of Chinese Medicine, Hefei, China
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19
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Chu X, Hou Y, Meng Q, Croteau DL, Wei Y, De S, Becker KG, Bohr VA. Nicotinamide adenine dinucleotide supplementation drives gut microbiota variation in Alzheimer’s mouse model. Front Aging Neurosci 2022; 14:993615. [PMID: 36185477 PMCID: PMC9520302 DOI: 10.3389/fnagi.2022.993615] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 08/22/2022] [Indexed: 11/13/2022] Open
Abstract
Alzheimer’s disease (AD) is the most common neurodegenerative disease. Growing evidence suggests an important role for gut dysbiosis and gut microbiota-host interactions in aging and neurodegeneration. Our previous works have demonstrated that supplementation with the nicotinamide adenine dinucleotide (NAD+) precursor, nicotinamide riboside (NR), reduced the brain features of AD, including neuroinflammation, deoxyribonucleic acid (DNA) damage, synaptic dysfunction, and cognitive impairment. However, the impact of NR administration on the intestinal microbiota of AD remains unknown. In this study, we investigated the relationship between gut microbiota and NR treatment in APP/PS1 transgenic (AD) mice. Compared with wild type (WT) mice, the gut microbiota diversity in AD mice was lower and the microbiota composition and enterotype were significantly different. Moreover, there were gender differences in gut microbiome between female and male AD mice. After supplementation with NR for 8 weeks, the decreased diversity and perturbated microbial compositions were normalized in AD mice. This included the species Oscillospira, Butyricicoccus, Desulfovibrio, Bifidobacterium, Olsenella, Adlercreutzia, Bacteroides, Akkermansia, and Lactobacillus. Our results indicate an interplay between NR and host-microbiota in APP/PS1 mice, suggesting that the effect of NR on gut dysbiosis may be an important component in its therapeutic functions in AD.
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Affiliation(s)
- Xixia Chu
- DNA Repair Section, National Institute on Aging, Baltimore, MD, United States
| | - Yujun Hou
- DNA Repair Section, National Institute on Aging, Baltimore, MD, United States
- Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, China
| | - Qiong Meng
- Laboratory of Genetics and Genomics, National Institute on Aging, Baltimore, MD, United States
| | - Deborah L. Croteau
- DNA Repair Section, National Institute on Aging, Baltimore, MD, United States
- Laboratory of Genetics and Genomics, National Institute on Aging, Baltimore, MD, United States
| | - Yong Wei
- DNA Repair Section, National Institute on Aging, Baltimore, MD, United States
| | - Supriyo De
- Laboratory of Genetics and Genomics, National Institute on Aging, Baltimore, MD, United States
| | - Kevin G. Becker
- Laboratory of Genetics and Genomics, National Institute on Aging, Baltimore, MD, United States
| | - Vilhelm A. Bohr
- DNA Repair Section, National Institute on Aging, Baltimore, MD, United States
- *Correspondence: Vilhelm A. Bohr,
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20
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De Giani A, Sandionigi A, Zampolli J, Michelotti A, Tursi F, Labra M, Di Gennaro P. Effects of Inulin-Based Prebiotics Alone or in Combination with Probiotics on Human Gut Microbiota and Markers of Immune System: A Randomized, Double-Blind, Placebo-Controlled Study in Healthy Subjects. Microorganisms 2022; 10:microorganisms10061256. [PMID: 35744774 PMCID: PMC9229734 DOI: 10.3390/microorganisms10061256] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/15/2022] [Accepted: 06/19/2022] [Indexed: 01/01/2023] Open
Abstract
The gut microbiota is implicated in diverse interactions affecting human health. The present study reports a randomized, double-blind, placebo-controlled clinical study conducted by administering a new synbiotic formulation composed of two Lactobacillus strains (L. plantarum and L. acidophilus) and one Bifidobacterium strain (B. animalis subsp. lactis) and two types of fructans (fructo-oligosaccharides with a degree of polymerization of 3–5 and inulin-type fructans with 10 DP). The effects of this synbiotic were evaluated on healthy subjects for 28 days and the maintenance of its efficacy was evaluated at the end of a follow-up period of 28 days. The synbiotic treatment contributes to higher biodiversity of the gut microbiota, increasing the community richness with respect to the group with the prebiotics alone and the placebo group. Its positive effect is also reflected in the variation of microbial community structure favoring the beneficial short-chain fatty acids bacterial producers. The amelioration of the health status of the subjects was also established by the reduction of common infectious disease symptom incidence, the stimulation of the gut immune system showing a noteworthy variation of fecal β-defensin2 and calprotectin levels, and the modulation of the response of the respiratory tract’s immune system by salivary IgA as well as total antioxidant capacity biomarkers.
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Affiliation(s)
- Alessandra De Giani
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza Della Scienza 2, 20126 Milano, MI, Italy; (A.D.G.); (A.S.); (J.Z.); (M.L.)
| | - Anna Sandionigi
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza Della Scienza 2, 20126 Milano, MI, Italy; (A.D.G.); (A.S.); (J.Z.); (M.L.)
| | - Jessica Zampolli
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza Della Scienza 2, 20126 Milano, MI, Italy; (A.D.G.); (A.S.); (J.Z.); (M.L.)
| | - Angela Michelotti
- Complife Italia S.r.l., Via Angelini 21, 27028 San Martino Siccomario, PV, Italy; (A.M.); (F.T.)
| | - Francesco Tursi
- Complife Italia S.r.l., Via Angelini 21, 27028 San Martino Siccomario, PV, Italy; (A.M.); (F.T.)
| | - Massimo Labra
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza Della Scienza 2, 20126 Milano, MI, Italy; (A.D.G.); (A.S.); (J.Z.); (M.L.)
| | - Patrizia Di Gennaro
- Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza Della Scienza 2, 20126 Milano, MI, Italy; (A.D.G.); (A.S.); (J.Z.); (M.L.)
- Correspondence: ; Tel.: +39-0264482949; Fax: +39-0264483450
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Hou K, Wu ZX, Chen XY, Wang JQ, Zhang D, Xiao C, Zhu D, Koya JB, Wei L, Li J, Chen ZS. Microbiota in health and diseases. Signal Transduct Target Ther 2022; 7:135. [PMID: 35461318 PMCID: PMC9034083 DOI: 10.1038/s41392-022-00974-4] [Citation(s) in RCA: 1165] [Impact Index Per Article: 388.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 03/11/2022] [Accepted: 03/15/2022] [Indexed: 02/07/2023] Open
Abstract
The role of microbiota in health and diseases is being highlighted by numerous studies since its discovery. Depending on the localized regions, microbiota can be classified into gut, oral, respiratory, and skin microbiota. The microbial communities are in symbiosis with the host, contributing to homeostasis and regulating immune function. However, microbiota dysbiosis can lead to dysregulation of bodily functions and diseases including cardiovascular diseases (CVDs), cancers, respiratory diseases, etc. In this review, we discuss the current knowledge of how microbiota links to host health or pathogenesis. We first summarize the research of microbiota in healthy conditions, including the gut-brain axis, colonization resistance and immune modulation. Then, we highlight the pathogenesis of microbiota dysbiosis in disease development and progression, primarily associated with dysregulation of community composition, modulation of host immune response, and induction of chronic inflammation. Finally, we introduce the clinical approaches that utilize microbiota for disease treatment, such as microbiota modulation and fecal microbial transplantation.
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Affiliation(s)
- Kaijian Hou
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Zhuo-Xun Wu
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Xuan-Yu Chen
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Jing-Quan Wang
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Dongya Zhang
- Microbiome Research Center, Moon (Guangzhou) Biotech Ltd, Guangzhou, 510535, China
| | - Chuanxing Xiao
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Dan Zhu
- Department of Endocrine and Metabolic Diseases, Longhu Hospital, The First Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Jagadish B Koya
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
| | - Liuya Wei
- School of Pharmacy, Weifang Medical University, Weifang, Shandong, 261053, China
| | - Jilin Li
- Department of Cardiovascular, The Second Affiliated Hospital of Medical College of Shantou University, Shantou, Guangdong, 515000, China
| | - Zhe-Sheng Chen
- Department of Pharmaceutical Sciences, Institute for Biotechnology, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA
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22
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Chenhuichen C, Cabello-Olmo M, Barajas M, Izquierdo M, Ramírez-Vélez R, Zambom-Ferraresi F, Martínez-Velilla N. Impact of probiotics and prebiotics in the modulation of the major events of the aging process: A systematic review of randomized controlled trials. Exp Gerontol 2022; 164:111809. [DOI: 10.1016/j.exger.2022.111809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 04/08/2022] [Accepted: 04/11/2022] [Indexed: 11/27/2022]
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23
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Meng C, Feng S, Hao Z, Dong C, Liu H. Changes in gut microbiota composition with age and correlations with gut inflammation in rats. PLoS One 2022; 17:e0265430. [PMID: 35290412 PMCID: PMC8923432 DOI: 10.1371/journal.pone.0265430] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 03/02/2022] [Indexed: 11/18/2022] Open
Abstract
Increasing evidences indicate that gut microbiota composition is associated with multiple inflammatory diseases. However, little is known about how gut microbiota changes with age and correlations with gut inflammation at sexual maturity stage of healthy individuals. Elucidating the dynamic changes of gut microbiota in healthy individuals at the sexual maturity stage and correlations with gut inflammation can provide clues for early risk assessment of gut diseases at the sexual maturity stage. Here, the shift in gut bacteria and its relationship with gut inflammation at the sexual maturity stage were explored. Sprague–Dawley rats at the sexual maturity stage were used in this study. 16S rRNA gene sequencing was performed to decipher gut bacteria shifts from the 7th week to the 9th week, and enzyme-linked immunosorbent assay (ELISA) was used to measure gut inflammation and gut barrier permeability. We found an increase in bacterial richness with age and a decrease in bacterial diversity with age. The gut bacteria were primarily dominated by the phyla Firmicutes and Bacteroides and the genus Prevotella. The relative abundance of Firmicutes increased with age, and the relative abundance of Bacteroides decreased with age. There was a positive correlation between body weight and the Firmicutes:Bacteroides ratio. More and more gut microbiota participated in the host gut inflammation and barrier permeability regulation with age. Ruminococcus was the only gut bacteria participated in gut inflammation and barrier permeability regulation both in the 7th week and the 15th week. These results provide a better understanding of the relationship between gut bacteria and gut inflammation in sexually mature rats and show that Ruminococcus may be a potential indicator for early risk assessment of gut inflammation.
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Affiliation(s)
- Chen Meng
- Institute of Environmental Biology and Life Support Technology, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Siyuan Feng
- Institute of Environmental Biology and Life Support Technology, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
| | - Zikai Hao
- Institute of Environmental Biology and Life Support Technology, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
- State Key Laboratory of Software Development Environment, Beihang University, Beijing, China
| | - Chen Dong
- Laboratory of Sport Nutrition and Intelligent Cooking, Shandong Sport University, Jinan, China
- * E-mail: (CD); (HL)
| | - Hong Liu
- Institute of Environmental Biology and Life Support Technology, School of Biological Science and Medical Engineering, Beihang University, Beijing, China
- International Joint Research Center of Aerospace Biotechnology & Medical Engineering, Beihang University, Beijing, China
- * E-mail: (CD); (HL)
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24
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Davinelli S, Scapagnini G. Interactions between dietary polyphenols and aging gut microbiota: A review. Biofactors 2022; 48:274-284. [PMID: 34559427 DOI: 10.1002/biof.1785] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 08/26/2021] [Indexed: 12/14/2022]
Abstract
Aging induces significant shifts in the composition of gut microbiota associated with decreased microbial diversity. Age-related changes in gut microbiota include a loss of commensals and an increase in disease-associated pathobionts. These alterations are accelerated by lifestyle factors, such as poor nutritional habits, physical inactivity, and medications. Given that diet is one of the main drivers shaping the gut microbiota, nutritional interventions for restoring gut homeostasis are of great importance to the overall health of older adults. Polyphenols, ubiquitously present in fruits and vegetables, have emerged as promising anti-aging candidates because of their ability to modulate some of the common denominators of aging, including gut dysbiosis. These compounds can influence the composition of the gut microbiota, and gut bacteria metabolize polyphenols into bioactive compounds that produce relevant health effects. Although the role of polyphenols on the aging gut has not been fully characterized, accumulating evidence suggests that these compounds exert selective effects on the gut microbial community. Here, we discuss the reciprocal interactions between polyphenols and gut microbiota and summarize the latest findings on the effects of polyphenols on modulating intestinal bacteria during aging.
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Affiliation(s)
- Sergio Davinelli
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
| | - Giovanni Scapagnini
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
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25
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Roviello G, Iannone LF, Bersanelli M, Mini E, Catalano M. The gut microbiome and efficacy of cancer immunotherapy. Pharmacol Ther 2022; 231:107973. [PMID: 34453999 DOI: 10.1016/j.pharmthera.2021.107973] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 07/07/2021] [Accepted: 07/27/2021] [Indexed: 12/14/2022]
Abstract
Cancer treatment has been deeply changed by immunotherapy, achieving unprecedented improvement in overall and progression-free survival in several advanced and metastatic cancers. Currently, immune checkpoint inhibitor (ICI) antibodies against cytotoxic T-lymphocyte antigen (CTLA-4) and programmed death/ligand 1 (PD-1/PD-L1) are being tested and approved for different tumors, ranging from melanoma to lung carcinoma. However, only a subgroup of patients can reach treatment benefits and long-term responses, and reliable biomarkers that can accurately predict clinical responses to immunotherapy are still unidentified. In the last decade, accumulating evidence seems to suggest the gut microbiota as one of the modulators that can alter the efficacy and toxicity of immunotherapy drugs (as well as chemotherapeutics), mainly acting through the local and systemic immune system. Herein, we reviewed the highly dynamic and complex microbiome-immune system interface, its bidirectional relationship with cancer immunotherapies, and explored the future possibilities and risks in manipulating the gut microbiome.
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Affiliation(s)
- Giandomenico Roviello
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy.
| | | | - Melissa Bersanelli
- Medical Oncology, University Hospital of Parma and Medicine and Surgery Department, University of Parma, Via Gramsci 14, 43126 Parma, Italy
| | - Enrico Mini
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy
| | - Martina Catalano
- Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy
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26
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Choi SI, Kim N, Nam RH, Park JH, Nho H, Yu JE, Song CH, Lee SM, Lee DH. Fecal Microbial Enterotypes Differentially Respond to a High-fat Diet Based on Sex in Fischer-344 Rats. J Cancer Prev 2021; 26:277-288. [PMID: 35047454 PMCID: PMC8749319 DOI: 10.15430/jcp.2021.26.4.277] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 12/23/2021] [Accepted: 12/24/2021] [Indexed: 11/03/2022] Open
Abstract
The gut microbiota interacts with the host gut environment, which is influenced by such factors as sex, age, and host diet. These factors induce changes in the microbial composition. The aim of this study was to identify differences in the gut microbiome of Fisher-344 (F344) rats fed a high-fat diet (HFD), depending on their age and sex. Fecal microbiomes from 6-, 31-, and 74-week-old, and 2-year-old both male and female rats (corresponding to 5-, 30-, 60-, and 80-year-old humans) were analyzed using 16S rRNA gene sequencing, phylogenetic investigation of communities by reconstruction of unobserved states, and enterotype (E) assessment. Moreover, the effect of an HFD on colonic epithelial cells was measured using real-time quantitative PCR. Alpha diversity decreased in the HFD group regardless of age and sex. Based on the enterotype clustering of the whole fecal microbiome, clusters from male rats were divided into E1 and E2 enterotypes, while clusters from female rats were divided into E1, E2, and E3 enterotypes. The female E3 group showed a significantly high abundance in the Ruminococcus genus and expression of Tlr2 mRNA, which may reflect compensation to the HFD. Moreover, the female E3 group showed a lower ratio of opportunistic pathogenic strains to commensal strains compared to the female E2 group. Administration of an HFD influenced the rat fecal microbiota in all assessed age groups, which could be further differentiated by sex. In particular, female rats showed a compensatory enterotype response to an HFD compared to male rats.
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Affiliation(s)
- Soo In Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Ryoung Hee Nam
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Heewon Nho
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jeong Eun Yu
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Chin-Hee Song
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Sun Min Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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27
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Wu L, Xie X, Liang T, Ma J, Yang L, Yang J, Li L, Xi Y, Li H, Zhang J, Chen X, Ding Y, Wu Q. Integrated Multi-Omics for Novel Aging Biomarkers and Antiaging Targets. Biomolecules 2021; 12:39. [PMID: 35053186 PMCID: PMC8773837 DOI: 10.3390/biom12010039] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 12/17/2021] [Accepted: 12/19/2021] [Indexed: 12/12/2022] Open
Abstract
Aging is closely related to the occurrence of human diseases; however, its exact biological mechanism is unclear. Advancements in high-throughput technology provide new opportunities for omics research to understand the pathological process of various complex human diseases. However, single-omics technologies only provide limited insights into the biological mechanisms of diseases. DNA, RNA, protein, metabolites, and microorganisms usually play complementary roles and perform certain biological functions together. In this review, we summarize multi-omics methods based on the most relevant biomarkers in single-omics to better understand molecular functions and disease causes. The integration of multi-omics technologies can systematically reveal the interactions among aging molecules from a multidimensional perspective. Our review provides new insights regarding the discovery of aging biomarkers, mechanism of aging, and identification of novel antiaging targets. Overall, data from genomics, transcriptomics, proteomics, metabolomics, integromics, microbiomics, and systems biology contribute to the identification of new candidate biomarkers for aging and novel targets for antiaging interventions.
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Affiliation(s)
- Lei Wu
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; (L.W.); (X.X.); (T.L.); (L.Y.); (J.Y.); (L.L.); (Y.X.); (H.L.); (J.Z.)
- School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China; (J.M.); (X.C.)
| | - Xinqiang Xie
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; (L.W.); (X.X.); (T.L.); (L.Y.); (J.Y.); (L.L.); (Y.X.); (H.L.); (J.Z.)
| | - Tingting Liang
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; (L.W.); (X.X.); (T.L.); (L.Y.); (J.Y.); (L.L.); (Y.X.); (H.L.); (J.Z.)
- School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China; (J.M.); (X.C.)
| | - Jun Ma
- School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China; (J.M.); (X.C.)
| | - Lingshuang Yang
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; (L.W.); (X.X.); (T.L.); (L.Y.); (J.Y.); (L.L.); (Y.X.); (H.L.); (J.Z.)
| | - Juan Yang
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; (L.W.); (X.X.); (T.L.); (L.Y.); (J.Y.); (L.L.); (Y.X.); (H.L.); (J.Z.)
- School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China; (J.M.); (X.C.)
| | - Longyan Li
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; (L.W.); (X.X.); (T.L.); (L.Y.); (J.Y.); (L.L.); (Y.X.); (H.L.); (J.Z.)
| | - Yu Xi
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; (L.W.); (X.X.); (T.L.); (L.Y.); (J.Y.); (L.L.); (Y.X.); (H.L.); (J.Z.)
| | - Haixin Li
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; (L.W.); (X.X.); (T.L.); (L.Y.); (J.Y.); (L.L.); (Y.X.); (H.L.); (J.Z.)
| | - Jumei Zhang
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; (L.W.); (X.X.); (T.L.); (L.Y.); (J.Y.); (L.L.); (Y.X.); (H.L.); (J.Z.)
| | - Xuefeng Chen
- School of Food and Biological Engineering, Shaanxi University of Science and Technology, Xi’an 710021, China; (J.M.); (X.C.)
| | - Yu Ding
- Department of Food Science and Technology, Institute of Food Safety and Nutrition, Jinan University, Guangzhou 510632, China
| | - Qingping Wu
- Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou 510070, China; (L.W.); (X.X.); (T.L.); (L.Y.); (J.Y.); (L.L.); (Y.X.); (H.L.); (J.Z.)
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28
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Li H, Ni J, Qing H. Gut Microbiota: Critical Controller and Intervention Target in Brain Aging and Cognitive Impairment. Front Aging Neurosci 2021; 13:671142. [PMID: 34248602 PMCID: PMC8267942 DOI: 10.3389/fnagi.2021.671142] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 05/07/2021] [Indexed: 12/12/2022] Open
Abstract
The current trend for the rapid growth of the global aging population poses substantial challenges for society. The human aging process has been demonstrated to be closely associated with changes in gut microbiota composition, diversity, and functional features. During the first 2 years of life, the gut microbiota undergoes dramatic changes in composition and metabolic functions as it colonizes and develops in the body. Although the gut microbiota is nearly established by the age of three, it continues to mature until adulthood, when it comprises more stable and diverse microbial species. Meanwhile, as the physiological functions of the human body deteriorated with age, which may be a result of immunosenescence and "inflammaging," the guts of elderly people are generally characterized by an enrichment of pro-inflammatory microbes and a reduced abundance of beneficial species. The gut microbiota affects the development of the brain through a bidirectional communication system, called the brain-gut-microbiota (BGM) axis, and dysregulation of this communication is pivotal in aging-related cognitive impairment. Microbiota-targeted dietary interventions and the intake of probiotics/prebiotics can increase the abundance of beneficial species, boost host immunity, and prevent gut-related diseases. This review summarizes the age-related changes in the human gut microbiota based on recent research developments. Understanding these changes will likely facilitate the design of novel therapeutic strategies to achieve healthy aging.
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Affiliation(s)
| | - Junjun Ni
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Sciences, Beijing Institute of Technology, Beijing, China
| | - Hong Qing
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Sciences, Beijing Institute of Technology, Beijing, China
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29
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Håkansson Å, Nuur Farma Megaelectra A, Persson J, Zhang S, Alsanius B, Olsson M, Jeppsson B. Immune response and gut microbiota of mice on a diet mimicking eating habits of elderly with risk of malnutrition development. Int J Food Sci Nutr 2021; 72:1071-1082. [PMID: 33840335 DOI: 10.1080/09637486.2021.1906212] [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] [Indexed: 10/21/2022]
Abstract
The number of elderlies is increasing but prevalence of malnutrition has been reported. The aim of the study was to determine the significance of short-term nutritional deficiencies in mice. Immune status was assessed through flow cytometry of leucocytes in Peyer's patches (PP) and mesenteric lymph nodes (MLN), and intestinal microbiota was evaluated by terminal restriction fragment length polymorphism (T-RFLP). C57BL/6NCrl mice fed standard diet (StD) or experimental diet high in fat, and low in carbohydrates, protein, fibre, vitamins, and minerals (ExpD) for 2 or 4 weeks. ExpD-animals gained less weight, increased liver lipids, and developed splenomegaly. Diet affected regulatory T-cells, gut homing receptors and TLR2 and TLR4 in PP and MLN and the microbiota was influenced. Partial least squares models on flow cytometry- and T-RFLP data demonstrated correlations between microbial communities and immune phenotyping. Our model shows similarities to malnourished elderly and interactions between intestinal bacteria and the immune system.
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Affiliation(s)
- Åsa Håkansson
- Department of Food Technology, Engineering and Nutrition, Chemical Center, Lund University, Lund, Sweden
| | | | - Jenny Persson
- Department of Food Technology, Engineering and Nutrition, Chemical Center, Lund University, Lund, Sweden
| | - Su Zhang
- Department of Clinical Sciences, Malmö, Surgery Research Unit and the Clinic of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden
| | - Beatrix Alsanius
- Department of Biosystems and Technology, Swedish University of Agricultural Sciences (SLU), Alnarp, Sweden
| | - Marie Olsson
- Department of Plant Breeding, SLU, Alnarp, Sweden
| | - Bengt Jeppsson
- Department of Clinical Sciences, Malmö, Surgery Research Unit and the Clinic of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden
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30
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Ojeda J, Ávila A, Vidal PM. Gut Microbiota Interaction with the Central Nervous System throughout Life. J Clin Med 2021; 10:1299. [PMID: 33801153 PMCID: PMC8004117 DOI: 10.3390/jcm10061299] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 03/12/2021] [Accepted: 03/17/2021] [Indexed: 02/08/2023] Open
Abstract
During the last years, accumulating evidence has suggested that the gut microbiota plays a key role in the pathogenesis of neurodevelopmental and neurodegenerative diseases via the gut-brain axis. Moreover, current research has helped to elucidate different communication pathways between the gut microbiota and neural tissues (e.g., the vagus nerve, tryptophan production, extrinsic enteric-associated neurons, and short chain fatty acids). On the other hand, altering the composition of gut microbiota promotes a state known as dysbiosis, where the balance between helpful and pathogenic bacteria is disrupted, usually stimulating the last ones. Herein, we summarize selected findings of the recent literature concerning the gut microbiome on the onset and progression of neurodevelopmental and degenerative disorders, and the strategies to modulate its composition in the search for therapeutical approaches, focusing mainly on animal models studies. Readers are advised that this is a young field, based on early studies, that is rapidly growing and being updated as the field advances.
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Affiliation(s)
- Jorge Ojeda
- Neuroimmunology and Regeneration of the Central Nervous System Unit, Biomedical Science Research Laboratory, Basic Sciences Department, Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción 4090541, Chile;
| | - Ariel Ávila
- Developmental Neurobiology Unit, Biomedical Science Research Laboratory, Basic Sciences Department, Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción 4090541, Chile;
| | - Pía M. Vidal
- Neuroimmunology and Regeneration of the Central Nervous System Unit, Biomedical Science Research Laboratory, Basic Sciences Department, Faculty of Medicine, Universidad Católica de la Santísima Concepción, Concepción 4090541, Chile;
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31
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Ale EC, Binetti AG. Role of Probiotics, Prebiotics, and Synbiotics in the Elderly: Insights Into Their Applications. Front Microbiol 2021; 12:631254. [PMID: 33584631 PMCID: PMC7876055 DOI: 10.3389/fmicb.2021.631254] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 01/04/2021] [Indexed: 12/17/2022] Open
Abstract
Elderly people are an important part of the global population who suffer from the natural processes of senescence, which lead to changes in the gut microbiota composition. These modifications have a great impact on their quality of life, bringing a general putrefactive and inflammatory status as a consequence. Some of the most frequent conditions related to this status are constipation, undernutrition, neurodegenerative diseases, susceptibility to opportunistic pathogens, and metabolic disbalance, among others. For these reasons, there is an increasing interest in improving their quality of life by non-invasive treatments such as the consumption of probiotics, prebiotics, and synbiotics. The aim of the present mini-review is to describe the benefits of these functional supplements/food according to the most recent clinical and pre-clinical studies published during the last decade. In addition, insights into several aspects we consider relevant to improve the quality of future studies are provided.
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Affiliation(s)
- Elisa C Ale
- Instituto de Lactología Industrial (CONICET-UNL), Facultad de Ingeniería Química (UNL), Santa Fe, Argentina
| | - Ana G Binetti
- Instituto de Lactología Industrial (CONICET-UNL), Facultad de Ingeniería Química (UNL), Santa Fe, Argentina
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32
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Lincoln KD. Race, Obesity, and Mental Health Among Older Adults in the United States: A Literature Review. Innov Aging 2020; 4:igaa031. [PMID: 32923693 PMCID: PMC7477914 DOI: 10.1093/geroni/igaa031] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Indexed: 12/24/2022] Open
Abstract
Rising rates of obesity among older adults in the United States are a serious public health concern. While the physical health consequences of obesity are well documented, the mental health consequences are less understood. This is especially the case among older adults in general and among racial and ethnic minority older adults in particular. Available studies document a link between obesity and a variety of mental health disorders. However, findings from this body of evidence are inconsistent, especially when race and ethnicity are considered. This article examines research on obesity and mental health among older adults and identifies risk factors, causal mechanisms, and methodological approaches that help clarify the equivocal nature of the literature. Promising research and future directions include studies that consider a wide array of contextual factors and population heterogeneity.
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Affiliation(s)
- Karen D Lincoln
- Suzanne Dworak-Peck School of Social Work, University of Southern California, Los Angeles
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33
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Lowe JR, Briggs AM, Whittle S, Stephenson MD. A systematic review of the effects of probiotic administration in inflammatory arthritis. Complement Ther Clin Pract 2020; 40:101207. [PMID: 32771911 DOI: 10.1016/j.ctcp.2020.101207] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2019] [Revised: 05/27/2020] [Accepted: 06/01/2020] [Indexed: 12/28/2022]
Abstract
OBJECTIVE To systematically identify and appraise evidence of the formulation specific effects and population specific responses of probiotics in inflammatory arthritis. METHODS MEDLINE (PubMed), CINAHL, EMBASE, and SCOPUS databases were searched for studies utilising probiotics in populations with inflammatory arthritis. The Joanna Briggs Institute (JBI) method was used to conduct the systematic review. A single reviewer undertook screening and data extraction. Two independent reviewers assessed the quality of evidence using JBI tools. RESULTS The search identified 5876 unique articles, with 154 potentially relevant full text articles retrieved. Twelve studies met the inclusion criteria and were included in the review, of which ten (83%) were randomised control trials (RCT) and two (17%) were quasi-experimental studies. Four studies included a variety of spondyloarthopathies (SpAs) and eight studies focused on rheumatoid arthritis (RA). Probiotics were supplied for a median of 60 days and mode of 56 days across all included studies (range 7-365 days). Overall, 17 different probiotics were supplied in colony forming units (CFU) per 24 hrs ranging from 1 × 108 to 2.25 × 1011. The order of probiotics supplied to the most participants and across the most studies was Lactobacillales. There was no statistical difference in the relative risk (RR) of minor adverse events between probiotic and control groups (RR 1.02, 95% CI 0.69 to 1.51) when including nil event studies. Meta-analysis identified a statistically significant benefit of probiotics on quality of life with a standard mean difference (SMD) of -0.37 (95% CI -0.59,-0.15) with subgroup analysis favouring Lactobacillales-only formulations. Small but statistically significant reductions in pain were identified, with a mean difference (MD) of -8.97 (95% CI-15.38, -2.56) on a 100mm visual analogue scale, independent of formulation. Meta-analysis confirmed the known statistically significant benefit of probiotics on the inflammatory marker C-reactive protein (CRP) concentration MD (mg/L) -2.33 (95% CI -4.26, -0.41), with subgroup analysis demonstrating a greater effect in RA and from combined Bifidobacteriales and Lactobacillales formulations. CONCLUSION This review indicates there may be differential benefits to combined formulations of Bifidobacteriales and Lactobacillales compared to purely Lactobacillales formulations, with respect to reducing pain, lowering CRP and improving quality of life. It also suggests variable benefits associated with the type of inflammatory arthritis. Relatively less benefit for lowering CRP was attributed to individuals with SpA compared to individuals with RA. Generalisability of results to clinical practice is limited by the dominant demographic of older individuals with established disease beyond the 'therapeutic window of intervention'. Small but statistically significant benefits require confirmation in clinical studies with greater consideration to potentially confounding factors of age, gender, diet and individual microbial signature.
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Affiliation(s)
- Judith R Lowe
- Joanna Briggs Institute, University of Adelaide, South Australia, Australia.
| | - Andrew M Briggs
- School of Physiotherapy and Exercise Science, Curtin University, Western Australia, Australia.
| | - Sam Whittle
- Department of Rheumatology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
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Piggott DA, Tuddenham S. The gut microbiome and frailty. Transl Res 2020; 221:23-43. [PMID: 32360945 PMCID: PMC8487348 DOI: 10.1016/j.trsl.2020.03.012] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 03/26/2020] [Accepted: 03/27/2020] [Indexed: 12/12/2022]
Abstract
The human microbiome is constituted by an extensive network of organisms that lie at the host/environment interface and transduce signals that play vital roles in human health and disease across the lifespan. Frailty is a critical aging-related syndrome marked by diminished physiological reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes including death. While recent studies suggest the microbiome may impact key pathways critical to frailty pathophysiology, direct evaluation of the microbiome-frailty relationship remains limited. In this article, we review the complex interplay of biological, behavioral, and environmental factors that may influence shifts in gut microbiome composition and function in aging populations and the putative implications of such shifts for progression to frailty. We discuss HIV infection as a key prototype for elucidating the complex pathways via which the microbiome may precipitate frailty. Finally, we review considerations for future research efforts.
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Affiliation(s)
- Damani A Piggott
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Maryland.
| | - Susan Tuddenham
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Potential prebiotic activities of soybean peptides Maillard reaction products on modulating gut microbiota to alleviate aging-related disorders in D-galactose-induced ICR mice. J Funct Foods 2020. [DOI: 10.1016/j.jff.2019.103729] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
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Kim M, Benayoun BA. The microbiome: An emerging key player in aging and longevity. TRANSLATIONAL MEDICINE OF AGING 2020. [DOI: 10.1016/j.tma.2020.07.004] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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Luo D, Chen K, Li J, Fang Z, Pang H, Yin Y, Rong X, Guo J. Gut microbiota combined with metabolomics reveals the metabolic profile of the normal aging process and the anti-aging effect of FuFang Zhenshu TiaoZhi(FTZ) in mice. Biomed Pharmacother 2019; 121:109550. [PMID: 31704617 DOI: 10.1016/j.biopha.2019.109550] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 10/06/2019] [Accepted: 10/08/2019] [Indexed: 12/19/2022] Open
Abstract
The aging process is accompanied by changes in the gut microbiota and metabolites. This study aimed to reveal the relationship between gut microbiota and the metabolome at different ages, as well as the anti-aging effect of FTZ, which is an effective clinical prescription for the treatment of hyperlipidemia and diabetes. METHODS In the present study, mice were randomly divided into different age and FTZ treatment groups. The aging-relevant behavioral phenotype the levels of blood glucose, cholesterol, triglycerides, low density lipoprotein cholesterol, free fatty acids, high density lipoprotein-cholesterol and cytokine TNF-α,IL-6, IL-8 in the serum were measured. Changes of serum metabolties were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-Q-TOF/MS). Gut microbiota were identified using 16S rDNA sequencing. RESULTS Our results indicated that with age, the aging-relevant behavioral phenotype appeared, glucose and lipid metabolism disordered, secretion levels of cytokine TNF-α, IL-6 and IL-8 increased.The Firmicutes/Bacteroidetes ratio changed with age, first increasing and then decreasing, and the microbial diversity and the community richness of the aging mice were improved by FTZ. The abundance of opportunistic bacteria decreased (Lactobacillus murinus, Erysipelatoclostridium), while the levels of protective bacteria such as Butyricimonas, Clostridium and Akkermansia increased. Metabolic analysis identified 24 potential biomarkers and 10 key pathways involving arachidonic acid metabolism, phospholipid metabolism, fatty acid metabolism, taurine and hypotaurine metabolism. Correlation analysis between the gut microbiota and biomarkers suggested that the relative abundance of protective bacteria was negatively correlated with the levels of leukotriene E4, 20-HETE and arachidonic acid, which was different from protective bacteria. CONCLUSION Shifts of gut microbiota and metabolomic profiles were observed in the mice during the normal aging process, and treatment with FTZ moderately corrected the aging, which may be mediated via interference with arachidonic acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, taurine and hypotaurine metabolism and gut microbiota in mice.
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Affiliation(s)
- Duosheng Luo
- Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China
| | - Kechun Chen
- Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China
| | - Jingbiao Li
- Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China
| | - Zhaoyan Fang
- Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China
| | - Huiting Pang
- Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China
| | - Yifan Yin
- Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China
| | - Xianglu Rong
- Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China
| | - Jiao Guo
- Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China; Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China.
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Cryan JF, O'Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, Codagnone MG, Cussotto S, Fulling C, Golubeva AV, Guzzetta KE, Jaggar M, Long-Smith CM, Lyte JM, Martin JA, Molinero-Perez A, Moloney G, Morelli E, Morillas E, O'Connor R, Cruz-Pereira JS, Peterson VL, Rea K, Ritz NL, Sherwin E, Spichak S, Teichman EM, van de Wouw M, Ventura-Silva AP, Wallace-Fitzsimons SE, Hyland N, Clarke G, Dinan TG. The Microbiota-Gut-Brain Axis. Physiol Rev 2019; 99:1877-2013. [PMID: 31460832 DOI: 10.1152/physrev.00018.2018] [Citation(s) in RCA: 2652] [Impact Index Per Article: 442.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
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Affiliation(s)
- John F. Cryan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Kenneth J. O'Riordan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Caitlin S. M. Cowan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Kiran V. Sandhu
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Thomaz F. S. Bastiaanssen
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Marcus Boehme
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Martin G. Codagnone
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Sofia Cussotto
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Christine Fulling
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Anna V. Golubeva
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Katherine E. Guzzetta
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Minal Jaggar
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Caitriona M. Long-Smith
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Joshua M. Lyte
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Jason A. Martin
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Alicia Molinero-Perez
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Gerard Moloney
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Emanuela Morelli
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Enrique Morillas
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Rory O'Connor
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Joana S. Cruz-Pereira
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Veronica L. Peterson
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Kieran Rea
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Nathaniel L. Ritz
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Eoin Sherwin
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Simon Spichak
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Emily M. Teichman
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Marcel van de Wouw
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Ana Paula Ventura-Silva
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Shauna E. Wallace-Fitzsimons
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Niall Hyland
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
| | - Timothy G. Dinan
- APC Microbiome Ireland, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland; Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland; and Department of Physiology, University College Cork, Cork, Ireland
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Dillon SM, Liu J, Purba CM, Christians AJ, Kibbie JJ, Castleman MJ, McCarter MD, Wilson CC. Age-related alterations in human gut CD4 T cell phenotype, T helper cell frequencies, and functional responses to enteric bacteria. J Leukoc Biol 2019; 107:119-132. [PMID: 31573727 DOI: 10.1002/jlb.5a0919-177rr] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Revised: 09/16/2019] [Accepted: 09/24/2019] [Indexed: 12/21/2022] Open
Abstract
Intestinal lamina propria (LP) CD4 T cells play critical roles in maintaining intestinal homeostasis and in immune responses to enteric microbes, yet little is known regarding whether they contribute to age-associated intestinal immune dysfunction. In this study, we evaluated the direct ex vivo frequency, activation/inhibitory phenotype, death profiles, and in vitro functional responses of human jejunum LP CD4 T cells, including Th1, Th17, and Th22 subsets isolated from younger (<45 years) and older (>65years) persons. Expression of the co-inhibitory molecule CTLA-4 was significantly lower in older CD4 T cells, whereas expression of HLA-DR, CD38, CD57, and PD-1 were not significantly different between groups. Total CD4 T cell frequencies were similar between age groups, but lower frequencies and numbers of Th17 cells were observed directly ex vivo in older samples. Older Th17 and Th1 cells proliferated to a lesser degree following in vitro exposure to bacterial antigens vs. their younger counterparts. Levels of spontaneous cell death were increased in older CD4 T cells; however, cellular death profiles following activation did not differ based on age. Thus, small intestinal CD4 T cells from older persons have altered phenotypic and functional profiles including reduced expression of a co-inhibitory molecule, increased spontaneous cell death, and both reduced frequencies and altered functional responses of specific Th cell subsets. These changes may contribute to altered intestinal homeostasis and loss of protective gut immunity with aging.
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Affiliation(s)
- Stephanie M Dillon
- Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jay Liu
- Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Christine M Purba
- Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Allison J Christians
- Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Jon J Kibbie
- Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Moriah J Castleman
- Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Martin D McCarter
- Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Cara C Wilson
- Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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Branca JJ, Gulisano M, Nicoletti C. Intestinal epithelial barrier functions in ageing. Ageing Res Rev 2019; 54:100938. [PMID: 31369869 DOI: 10.1016/j.arr.2019.100938] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 07/19/2019] [Accepted: 07/24/2019] [Indexed: 12/11/2022]
Abstract
The intestinal epithelial barrier protects the mucosa of the gastrointestinal (GI)-tract and plays a key role in maintaining the host homeostasis. It encompasses several elements that include the intestinal epithelium and biochemical and immunological products, such as the mucus layer, antimicrobial peptides (AMPs) and secretory immunologlobulin A (sIgA). These components are interlinked with the large microbial community inhabiting the gut to form a highly sophisticated biological system that plays an important role on many aspects of human health both locally and systemically. Like any other organ and tissue, the intestinal epithelial barrier is affected by the ageing process. New insights have surfaced showing that critical functions, including intestinal stem cell regeneration and regulation of the intestinal crypt homeostasis, barrier integrity, production of regulatory cytokines, and epithelial innate immunity to pathogenic antigens change across life. Here we review the age-associated changes of the various components of the intestinal epithelial barrier and we highlight the necessity to elucidate further the mechanisms underlying these changes. Expanding our knowledge in this area is a goal of high medical relevance and it will help to define intervention strategies to ameliorate the quality of life of the ever-expanding elderly population.
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Casati M, Ferri E, Azzolino D, Cesari M, Arosio B. Gut microbiota and physical frailty through the mediation of sarcopenia. Exp Gerontol 2019; 124:110639. [PMID: 31226349 DOI: 10.1016/j.exger.2019.110639] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 06/12/2019] [Accepted: 06/17/2019] [Indexed: 12/18/2022]
Abstract
The changing physiology and lifestyle of older people affect the gut microbiota composition. In particular, the age-related diet modifications can alter the gut microbiota biodiversity and determine the relative abundance of specific microbial taxa, resulting in microbiota dysbiosis with negative consequences for the host physiology. Unhealthy microbiota may then induce an acceleration of the age-related physiological changes, consequently concurring at determining the characteristic complexity of frail older persons. One of the major clinical manifestations of frailty is represented by the individual's physical decline. Besides of a well-established clinical phenotype of frailty, the qualitative and quantitative skeletal muscle impairment (i.e., sarcopenia) is today of particular interest for potentially serving as target for (pharmacological and non-pharmacological) interventions to prevent incident disability. Evidence suggests that gut microbiota is able to influence the skeletal muscle homeostasis via microbiota-dependent metabolites, thus representing the possible biological substratum for the sarcopenia onset. In fact, the rearrangements of gut microbiota as well as the alteration of its functions contribute at increasing the anabolic resistance, releasing pro-inflammatory mediators, determining mitochondrial abnormalities with consequent oxidation, and causing insulin resistance. In this article, the link between gut microbiota and physical frailty is discussed. It is especially explained the role that sarcopenia may play in this likely bidirectional relationship.
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Affiliation(s)
- Martina Casati
- Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy.
| | - Evelyn Ferri
- Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy.
| | - Domenico Azzolino
- Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Via Pace 9, 20122 Milan, Italy.
| | - Matteo Cesari
- Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Via Pace 9, 20122 Milan, Italy.
| | - Beatrice Arosio
- Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Via Pace 9, 20122 Milan, Italy.
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Smith LK, Wissel EF. Microbes and the Mind: How Bacteria Shape Affect, Neurological Processes, Cognition, Social Relationships, Development, and Pathology. PERSPECTIVES ON PSYCHOLOGICAL SCIENCE 2019; 14:397-418. [DOI: 10.1177/1745691618809379] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Recent data suggest that the human body is not so exclusively human after all. Specifically, humans share their bodies with approximately 10 trillion microorganisms, collectively known as the microbiome. Chief among these microbes are bacteria, and there is a growing consensus that they are critical to virtually all facets of normative functioning. This article reviews the ways in which bacteria shape affect, neurological processes, cognition, social relationships, development, and psychological pathology. To date, the vast majority of research on interactions between microbes and humans has been conducted by scientists outside the field of psychology, despite the fact that psychological scientists are experts in many of the topics being explored. This review aims to orient psychological scientists to the most relevant research and perspectives regarding the microbiome so that we might contribute to the now widespread, interdisciplinary effort to understand the relationship between microbes and the mind.
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Affiliation(s)
- Leigh K. Smith
- Department of Psychology, University of California, Davis
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Liu J, Johnson R, Dillon S, Kroehl M, Frank DN, Tuncil YE, Zhang X, Ir D, Robertson CE, Seifert S, Higgins J, Hamaker B, Wilson CC, Erlandson KM. Among older adults, age-related changes in the stool microbiome differ by HIV-1 serostatus. EBioMedicine 2019; 40:583-594. [PMID: 30685386 PMCID: PMC6413415 DOI: 10.1016/j.ebiom.2019.01.033] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 01/14/2019] [Accepted: 01/14/2019] [Indexed: 12/18/2022] Open
Abstract
Background HIV-1 infection and physiological aging are independently linked to elevated systemic inflammation and changes in enteric microbial communities (dysbiosis). However, knowledge of the direct effect of HIV infection on the aging microbiome and potential links to systemic inflammation is lacking. Methods In a cross-sectional study of older people living with HIV (PLWH) (median age 61.5 years, N = 14) and uninfected controls (median 58 years, n = 22) we compared stool microbiota, levels of microbial metabolites (short-chain fatty acid levels, SCFA) and systemic inflammatory biomarkers by HIV serostatus and age. Findings HIV and age were independently associated with distinct changes in the stool microbiome. For example, abundances of Enterobacter and Paraprevotella were higher and Eggerthella and Roseburia lower among PLWH compared to uninfected controls. Age-related microbiome changes also differed by HIV serostatus. Some bacteria with inflammatory potential (e.g. Escherichia) increased with age among PLWH, but not controls. Stool SCFA levels were similar between the two groups yet patterns of associations between individual microbial taxa and SCFA levels differed. Abundance of various genera including Escherichia and Bifidobacterium positively associated with inflammatory biomarkers (e.g. soluble Tumor Necrosis Factor Receptors) among PLWH, but not among controls. Interpretation The age effect on the gut microbiome and associations between microbiota and microbial metabolites or systemic inflammation differed based on HIV serostatus, raising important implications for the impact of therapeutic interventions, dependent on HIV serostatus or age.
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Affiliation(s)
- Jay Liu
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Rachel Johnson
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA
| | - Stephanie Dillon
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Miranda Kroehl
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA
| | - Daniel N Frank
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Yunus E Tuncil
- Food Engineering Department, Ordu University, Ordu, Turkey; Department of Food Science, Purdue University, Lafayette, IN, USA
| | - Xiaowei Zhang
- Department of Food Science, Purdue University, Lafayette, IN, USA
| | - Diana Ir
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Charles E Robertson
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Sharon Seifert
- Department of Pharmacology, Children's Hospital Colorado, Aurora, CO, USA
| | - Janine Higgins
- Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Bruce Hamaker
- Department of Food Science, Purdue University, Lafayette, IN, USA
| | - Cara C Wilson
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
| | - Kristine M Erlandson
- Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
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What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases. Microorganisms 2019; 7:microorganisms7010014. [PMID: 30634578 PMCID: PMC6351938 DOI: 10.3390/microorganisms7010014] [Citation(s) in RCA: 1989] [Impact Index Per Article: 331.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Revised: 12/15/2018] [Accepted: 01/09/2019] [Indexed: 02/06/2023] Open
Abstract
Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human's gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host⁻microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.
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Aging, Immunity, and Neuroinflammation: The Modulatory Potential of Nutrition. NUTRITION AND IMMUNITY 2019. [PMCID: PMC7123246 DOI: 10.1007/978-3-030-16073-9_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/03/2022]
Abstract
Aging influences an organism’s entire physiology, affecting functions at the molecular, cellular, and systemic levels and increasing susceptibility to many major chronic diseases. The changes in the immune system that accompany human aging are very complex and are generally referred to as immunosenescence. The factors and mechanisms of immunosenescence are multiple and include, among others, defects in the bone marrow, thymic involution, and intrinsic defects in the formation, maturation, homeostasis, and migration of peripheral lymphocytes. Aging affects both the innate and adaptive arms of the immune system. The process of aging is commonly accompanied by low-grade inflammation thought to contribute to neuroinflammation and to many age-related diseases. Numerous attempts to define the role of chronic inflammation in aging have implicated chronic oxidative stress, mitochondrial damage, immunosenescence, epigenetic modifications, and other phenomena. Several lifestyle strategies, such as intervening to provide an adequate diet and physical and mental activity, have been shown to result in improved immune and neuroprotective functions, a decrease in oxidative stress and inflammation, and a potential increase in individual longevity. The studies published thus far describe a critical role for nutrition in maintaining the immune response of the aged, but they also indicate the need for a more in-depth, holistic approach to determining the optimal nutritional and behavioral strategies that would maintain immune and other physiological systems in elderly people. In this chapter, we focus first on the age-related changes of the immune system. Further, we discuss possible deleterious influences of immunosenescence and low-grade inflammation (inflammaging) on neurodegenerative processes in the normally aging brain. Finally, we consider our current understanding of the modulatory potential of nutrition that may mediate anti-inflammatory effects and thus positively affect immunity and the aging brain.
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Xu K, Guo Y, Li Z, Wang Z. Aging Biomarkers and Novel Targets for Anti-Aging Interventions. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1178:39-56. [PMID: 31493221 DOI: 10.1007/978-3-030-25650-0_3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The aging population worldwide is expanding at an increasing rate. By 2050, approximately a quarter of the world population will consist of the elderly. To slow down the aging process, exploration of aging biomarkers and the search for novel antiaging targets have attracted much interest. Nonetheless, because aging research is costly and time-consuming and the aging process is complicated, aging research is considered one of the most difficult biological fields. Here, providing a broader definition of aging biomarkers, we review cutting-edge research on aging biomarkers at the molecular, cellular, and organismal levels, thus shedding light on the relations between aging and telomeres, longevity proteins, a senescence-associated secretory phenotype, the gut microbiota and metabolic patterns. Furthermore, we evaluate the suitability of these aging biomarkers for the development of novel antiaging targets on the basis of the most recent research on this topic. We also discuss the possible implications and some controversies regarding these biomarkers for therapeutic interventions in aging and age-related disease processes. We have attempted to cover all of the latest research on aging biomarkers in our review but there are countless studies on aging biomarkers, and the topic of aging interventions will continue to deepen even further. We hope that our review can serve as a reference for better characterization of aging and as inspiration for the screening of antiaging drugs as well as give some clues to further research into aging biomarkers and antiaging targets.
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Affiliation(s)
- Kang Xu
- Protein Science Key Laboratory of the Ministry of Education, School of Pharmaceutical Sciences, Tsinghua University, Beijing, People's Republic of China
| | - Yannan Guo
- Protein Science Key Laboratory of the Ministry of Education, School of Pharmaceutical Sciences, Tsinghua University, Beijing, People's Republic of China
| | - Zhongchi Li
- Protein Science Key Laboratory of the Ministry of Education, School of Pharmaceutical Sciences, Tsinghua University, Beijing, People's Republic of China
| | - Zhao Wang
- Protein Science Key Laboratory of the Ministry of Education, School of Pharmaceutical Sciences, Tsinghua University, Beijing, People's Republic of China.
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Prattichizzo F, Giuliani A, Mensà E, Sabbatinelli J, De Nigris V, Rippo MR, La Sala L, Procopio AD, Olivieri F, Ceriello A. Pleiotropic effects of metformin: Shaping the microbiome to manage type 2 diabetes and postpone ageing. Ageing Res Rev 2018; 48:87-98. [PMID: 30336272 DOI: 10.1016/j.arr.2018.10.003] [Citation(s) in RCA: 77] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 09/13/2018] [Accepted: 10/10/2018] [Indexed: 02/06/2023]
Abstract
Metformin is the first-choice therapy to lower glycaemia and manage type 2 diabetes. Continuously emerging epidemiological data and experimental models are showing additional protective effects of metformin against a number of age-related diseases (ARDs), e.g., cardiovascular diseases and cancer. This evidence has prompted the design of a specific trial, i.e., the Targeting Aging with Metformin (TAME) trial, to test metformin as an anti-ageing molecule. However, a unifying or prevailing mechanism of action of metformin is still debated. Here, we summarize the epidemiological data linking metformin to ARD prevention. Then, we dissect the deeply studied mechanisms of action explaining its antihyperglycemic effect and the putative mechanisms supporting its anti-ageing properties, focusing on studies using clinically pertinent doses. We hypothesize that the molecular observations obtained in different models with metformin could be indirectly mediated by its effect on gut flora. Novel evidence suggests that metformin reshapes the human microbiota, promoting the growth of beneficial bacterial species and counteracting the expansion of detrimental bacterial species. In turn, this action would influence the balance between pro- and anti-inflammatory circulating factors, thereby promoting glycaemic control and healthy ageing. This framework may reconcile diverse observations, providing information for designing further studies to elucidate the complex interplay between metformin and the metabiome harboured in mammalian body compartments, thereby paving the way for innovative, bacterial-based therapeutics to manage type 2 diabetes and foster a longer healthspan.
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Affiliation(s)
| | - Angelica Giuliani
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| | - Emanuela Mensà
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| | - Jacopo Sabbatinelli
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| | - Valeria De Nigris
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Maria Rita Rippo
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy
| | | | - Antonio Domenico Procopio
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy; Center of Clinical Pathology and Innovative Therapy, Italian National Research Centre on Aging, IRCCS INRCA, Ancona, Italy
| | - Fabiola Olivieri
- Department of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy; Center of Clinical Pathology and Innovative Therapy, Italian National Research Centre on Aging, IRCCS INRCA, Ancona, Italy
| | - Antonio Ceriello
- IRCCS MultiMedica, Milan, Italy; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Spain
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Lee SM, Kim N, Yoon H, Nam RH, Lee DH. Microbial Changes and Host Response in F344 Rat Colon Depending on Sex and Age Following a High-Fat Diet. Front Microbiol 2018; 9:2236. [PMID: 30298061 PMCID: PMC6160749 DOI: 10.3389/fmicb.2018.02236] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Accepted: 09/03/2018] [Indexed: 12/14/2022] Open
Abstract
Gut microbiota, an important component that affects host health, change rapidly and directly in response to altered diet composition. Recently, the role of diet–microbiome interaction on the development of colon cancer has been the focus of interest. Colon cancer occurs more frequently in an aged population, and in males. However, the effect of dietary changes on the gut microbiome has been studied mainly in young males, even though it may vary with age and sex. The aim of this study was to investigate microbial changes and host response in the colons of male and female 6-week-old (young) and 2-year-old (old) Fisher-344 rats exposed to a high-fat diet (HFD). Our results showed that exposure to HFD for 8 weeks decreased the species richness of microbiota (Chao1) and increased Firmicutes/Bacteroidetes ratio only in aged rats, and not in young rats. Sex differences underlying the alteration by HFD in the gut microbiome were observed in the microbiome of aged rats. For instance, the abundance ratio of Akkermansia muciniphila and Desulfovibrio spp. increased in response to HFD in young rats and female aged rats, but not in male aged rats. Histological inflammation and cell proliferation of colon mucosa (indexed by Ki67) were significantly increased by HFD even in young rats; aged rats showed significantly higher cell proliferation in the HFD group than in the control. The HFD-induced decrease of species richness and the increase in specific species (Desulfovibrio spp. and Clostridium lavalense), which produce carcinogenic compounds such as H2S and N-nitroso compounds, were significantly correlated with Ki67 index. In colon mucosa, the concentration of myeloperoxidase was increased by HFD only in males, and not in females. In conclusion, the results suggest a link between HFD-induced gut dysbiosis (particularly the low species richness and high abundance ratios of Desulfovibrio spp. and C. lavalense) and cell proliferation of colon mucosa (indicated by Ki67 IHC). In addition, sex differences influence the response of gut microbiome to HFD particularly in old age. Such sex differences in the gut microbiota might be related to sex differences in inflammation in the colon mucosa.
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Affiliation(s)
- Sun Min Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.,Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, South Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Ryoung Hee Nam
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.,Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea.,Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul, South Korea
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Wu J, Ren W, Li L, Luo M, Xu K, Shen J, Wang J, Chang G, Lu Y, Qi Y, Xu B, He Y, Hu Y. Effect of Aging and Glucagon-like Peptide 2 on Intestinal Microbiota in SD Rats. Aging Dis 2018; 9:566-577. [PMID: 30090647 PMCID: PMC6065291 DOI: 10.14336/ad.2017.1001] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2017] [Accepted: 10/01/2017] [Indexed: 01/24/2023] Open
Abstract
Recent research suggests that intestinal microbiota affect the aging process. Glucagon-like peptide 2 (GLP-2), a growth factor found in the intestinal mucosal epithelium, reduces intestinal permeability and affects intestinal microbiota. The relationship between aging, GLP-2, and intestinal microbiota are still not well understood. The current study examined the influence of aging and GLP-2 on the intestinal microbiota of rats. Twelve 3-month old male SD rats were randomly divided into two groups: a young control group (group C) and a young GLP-2 treatment group (group G). Twelve 26-month old male SD rats were randomly divided into two groups: an aged control group (group L) and an aged GLP-2 treatment group (group T). GLP-2 was intraperitoneally injected into rats from group G and group T for 14 days. Plasma GLP-2 concentration was evaluated by ELISA tests. Fresh intestinal stool samples were collected from each group and total fecal bacterial genomic DNA was extracted from the associated rats. The bacterial composition of fecal samples was analyzed by Miseq high-throughput sequencing and comparison with SRA databases. Overall, the diversity of intestinal microbiota significantly decreases with age in SD rats, while GLP-2 has no significant effect on the diversity of intestinal microbiota. Upon aging, there is a reduction in probiotic bacteria and a concomitant increase in pathogenic bacteria in rats. Treatment with GLP-2 results in a significant reduction in the prevalence of pathogenic bacterial genera and an increase in some potential benefit bacteria in aged rats. In addition, treatment with GLP-2 results in an increase in several probiotics and a reduction in the prevalence of pathogenic bacterial genera in young rats.
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Affiliation(s)
- Jiayu Wu
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Weiying Ren
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Li Li
- 2Department of Internal Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Man Luo
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Kan Xu
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jiping Shen
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jia Wang
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Guilin Chang
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yi Lu
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yiming Qi
- 2Department of Internal Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Binger Xu
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yuting He
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yu Hu
- 1Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai 200032, China
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Zeng X, Su W, Liu H, Zheng Y, Chen T, Zhang W, Yan Z, Bai Y, Yao H. Simultaneous determination of rosuvastatin, naringin and naringenin in rat plasma by RRLC-MS/MS and its application to a pharmacokinetic drug interaction study. J Chromatogr Sci 2018; 56:611-618. [PMID: 29701749 DOI: 10.1093/chromsci/bmy034] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2017] [Accepted: 04/04/2018] [Indexed: 01/12/2023]
Abstract
A rapid resolution liquid chromatography tandem mass spectrometry method was developed and validated for simultaneous determination of rosuvastatin, naringin and naringenin in rat plasma. Chromatographic separation of analytes and internal standard (fluvastatin for rosuvastatin, while isoquercitrin for naringin and naringenin) was performed on Agilent Poroshell 120 EC-C18 column (3.0 × 50 mm, 2.7 μm) using gradient elution with a mobile phase of methanol and water, both with 0.1% formic acid (v/v). The detection was operated in multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 579.1→270.8 for naringin, m/z 270.9→150.7 for naringenin, m/z 463.1→299.8 for isoquercitrin in negative ionization mode, and m/z 482.2→258.1 for rosuvastatin, m/z 412.1→224.1 for fluvastatin in positive ionization mode. Polarity switch (negative-positive-negative ionization mode) was performed in a total runtime of 5.0 min. The method was validated over a concentration range of 10-2,000 ng/mL for the above three analytes. The intra-day and inter-day precisions and accuracies of the quality control samples at low, medium and high concentration levels exhibited relative standard deviations <10% and the accuracy values ranged from -7.2% to 8.4%. The proposed method was successfully applied to the pharmacokinetic drug interaction study of rosuvastatin combined with naringin in rats.
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Affiliation(s)
- Xuan Zeng
- Guangdong Key Laboratory of Plant Resources, Guangdong Engineering and Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou, People's Republic of China
| | - Weiwei Su
- Guangdong Key Laboratory of Plant Resources, Guangdong Engineering and Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou, People's Republic of China
| | - Hong Liu
- Guangdong Key Laboratory of Plant Resources, Guangdong Engineering and Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou, People's Republic of China
| | - Yuying Zheng
- Guangdong Key Laboratory of Plant Resources, Guangdong Engineering and Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou, People's Republic of China
| | - Taobin Chen
- Guangdong Key Laboratory of Plant Resources, Guangdong Engineering and Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou, People's Republic of China
| | - Weijian Zhang
- Guangdong Key Laboratory of Plant Resources, Guangdong Engineering and Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou, People's Republic of China
| | - Zenghao Yan
- Guangdong Key Laboratory of Plant Resources, Guangdong Engineering and Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou, People's Republic of China
| | - Yang Bai
- Guangdong Key Laboratory of Plant Resources, Guangdong Engineering and Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou, People's Republic of China
| | - Hongliang Yao
- Guangdong Key Laboratory of Plant Resources, Guangdong Engineering and Technology Research Center for Quality and Efficacy Reevaluation of Post-Market Traditional Chinese Medicine, School of Life Sciences, Sun Yat-sen University, No. 135, Xingang Xi Road, Guangzhou, People's Republic of China
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