scholarly journals A novel probiotics therapy for aging-related leaky gut and inflammation

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 672-672
Author(s):  
Shaohua Wang ◽  
Bo Wang ◽  
Sidharth Mishra ◽  
Shalini Jain ◽  
Jingzhong Ding ◽  
...  
Keyword(s):  
Older Adults ◽  
Gut Microbiota ◽  
Tight Junctions ◽  
The Elderly ◽  
Human Infant ◽  
Bile Salt Hydrolase ◽  
Low Grade ◽  
Human Origin ◽  
Leaky Gut ◽  
Healthy Human

Abstract Inflammaging characterized with increased low grade inflammation in older adults is common determinant of unhealthy aging; and is a major risk factor of morbidity and mortality in older adults. The precise origin of inflammation in older adults is not known, however, emerging evidence indicate that increased intestinal epithelial permeability (leaky gut) and abnormal (dysbiotic) gut microbiota could be one of the key source. However, no preventive and treatment therapies are available to reverse the leaky gut and microbiome dysbiosis in older adults. Here, we presented the evidence that a human-origin probiotics cocktail containing 5 Lactobacillus and 5 Enterococcus strains isolated from healthy human infant gut can ameliorate aging-related metabolic, physical and cognitive dysfunctions in older mice. We show that the Feeding this probiotic cocktail prevented high-fat diet–induced (HFD-induced) abnormalities in glycose metabolism and physical functions in older mice and reduced microbiota dysbiosis, leaky gut, inflammation. Probiotic-modulated gut microbiota reduced leaky gut by increasing tight junctions on intestinal epithelia, which in turn reduced inflammation. Mechanistically, probiotics increased bile salt hydrolase activity in older microbiota, which in turn increased taurine deconjugation from bile acids to increase free taurine abundance in the gut. We further show that taurine stimulated tight junctions and suppressed gut leakiness. Further, taurine increased life span, reduced adiposity and leaky gut, and enhanced physical function in Caenorhabditis elegans. Whether this novel human origin probiotic therapy could prevent or treat aging-related leaky gut and inflammation in the elderly by reversing microbiome dysbiosis requires evaluation.

scholarly journals Metformin Reduces Aging-Related Leaky Gut and Improves Cognitive Function by Beneficially Modulating Gut Microbiome/Goblet Cell/Mucin Axis

2020 ◽  
Vol 75 (7) ◽  
pp. e9-e21 ◽  
Author(s):  
Shokouh Ahmadi ◽  
Atefeh Razazan ◽  
Ravinder Nagpal ◽  
Shalini Jain ◽  
Bo Wang ◽  
...  
Keyword(s):  
Older Adults ◽  
Goblet Cell ◽  
Gut Microbiome ◽  
Cell Mass ◽  
Low Grade ◽  
Leaky Gut ◽  
High Fat ◽  
Differentiation Markers ◽  
Mucin Production ◽  
Goblet Cell Differentiation

Abstract Aging-related illnesses are increasing and effective strategies to prevent and/or treat them are lacking. This is because of a poor understanding of therapeutic targets. Low-grade inflammation is often higher in older adults and remains a key risk factor of aging-related morbidities and mortalities. Emerging evidence indicates that abnormal (dysbiotic) gut microbiome and dysfunctional gut permeability (leaky gut) are linked with increased inflammation in older adults. However, currently available drugs do not treat aging-related microbiome dysbiosis and leaky gut, and little is known about the cellular and molecular processes that can be targeted to reduce leaky gut in older adults. Here, we demonstrated that metformin, a safe Food and Drug Administration-approved antidiabetic drug, decreased leaky gut and inflammation in high-fat diet-fed older obese mice, by beneficially modulating the gut microbiota. In addition, metformin increased goblet cell mass and mucin production in the obese older gut, thereby decreasing leaky gut and inflammation. Mechanistically, metformin increased the goblet cell differentiation markers by suppressing Wnt signaling. Our results suggest that metformin can be used as a regimen to prevent and treat aging-related leaky gut and inflammation, especially in obese individuals and people with western-style high-fat dietary lifestyle, by beneficially modulating gut microbiome/goblet cell/mucin biology.

scholarly journals Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001037 ◽  
Author(s):  
Jean-Marie Berthelot ◽  
Jérémie Sellam ◽  
Yves Maugars ◽  
Francis Berenbaum
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Cartilage Degradation ◽  
Low Grade ◽  
New Paradigm ◽  
Healthy Human ◽  
Human Cartilage ◽  
Intact Cartilage ◽  
Low Grade Inflammation

DNA of gut microbiota can be found in synovium of osteoarthritis and rheumatoid arthritis. This finding could result from the translocation of still alive bacteria from gut to joints through blood, since the diversified dormant microbiota of healthy human blood can be transiently resuscitated in vitro. The recent finding of gut microbiome in human cartilage, which differed between osteoarthritis and controls, suggests that a similar trafficking of dead or alive bacteria from gut microbiota physiologically occurs between gut and epiphysial bone marrow. Subchondral microbiota could enhance cartilage healing and transform components of deep cartilage matrix in metabolites with immunosuppressive properties. The differences of microbiome observed between hip and knee cartilage, either in osteoarthritis or controls, might be the counterpart of subtle differences in chondrocyte metabolism, themselves in line with differences in DNA methylation according to joints. Although bacteria theoretically cannot reach chondrocytes from the surface of intact cartilage, some bacteria enter the vascular channels of the epiphysial growth cartilage in young animals, whereas others can infect chondrocytes in vitro. In osteoarthritis, the early osteochondral plate angiogenesis may further enhance the ability of microbiota to locate close to the deeper layers of cartilage, and this might lead to focal dysbiosis, low-grade inflammation, cartilage degradation, epigenetic changes in chondrocytes and worsening of osteoarthritis. More studies on cartilage across different ethnic groups, weights, and according to age, are needed, to confirm the silent presence of gut microbiota close to human cartilage and better understand its physiologic and pathogenic significance.

scholarly journals The Roles of the Gut Microbiota and Chronic Low-Grade Inflammation in Older Adults With Frailty

2021 ◽  
Vol 11 ◽  
Author(s):  
YuShuang Xu ◽  
XiangJie Liu ◽  
XiaoXia Liu ◽  
Di Chen ◽  
MengMeng Wang ◽  
...  
Keyword(s):  
Older Adults ◽  
Gut Microbiota ◽  
Chronic Inflammation ◽  
Healthy Aging ◽  
Low Grade ◽  
Age Related ◽  
Composition Structure ◽  
Low Grade Inflammation

Frailty is a major public issue that affects the physical health and quality of life of older adults, especially as the population ages. Chronic low-grade inflammation has been speculated to accelerate the aging process as well as the development of age-related diseases such as frailty. Intestinal homeostasis plays a crucial role in healthy aging. The interaction between the microbiome and the host regulates the inflammatory response. Emerging evidence indicates that in older adults with frailty, the diversity and composition structure of gut microbiota are altered. Age-associated changes in gut microbiota composition and in their metabolites contribute to increased gut permeability and imbalances in immune function. In this review, we aim to: identify gut microbiota changes in the aging and frail populations; summarize the role of chronic low-grade inflammation in the development of frailty; and outline how gut microbiota may be related to the pathogenesis of frailty, more specifically, in the regulation of gut-derived chronic inflammation. Although additional research is needed, the regulation of gut microbiota may represent a safe, easy, and inexpensive intervention to counteract the chronic inflammation leading to frailty.

scholarly journals Differences in Gut Microbiome Composition between Senior Orienteering Athletes and Community-Dwelling Older Adults

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2610
Author(s):  
Frida Fart ◽  
Sukithar Kochappi Rajan ◽  
Rebecca Wall ◽  
Ignacio Rangel ◽  
John Peter Ganda-Mall ◽  
...  
Keyword(s):  
Older Adults ◽  
Gut Microbiota ◽  
Gastrointestinal Symptoms ◽  
Well Being ◽  
The Elderly ◽  
Community Dwelling ◽  
Physically Active ◽  
Gastrointestinal Health ◽  
Faecalibacterium Prausnitzii ◽  
Community Dwelling Older Adults

Background: Gastrointestinal (GI) health is an important aspect of general health. Gastrointestinal symptoms are of specific importance for the elderly, an increasing group globally. Hence, promoting the elderly’s health and especially gastrointestinal health is important. Gut microbiota can influence gastrointestinal health by modulation of the immune system and the gut–brain axis. Diverse gut microbiota have been shown to be beneficial; however, for the elderly, the gut microbiota is often less diverse. Nutrition and physical activity, in particular, are two components that have been suggested to influence composition or diversity. Materials and Methods: In this study, we compared gut microbiota between two groups of elderly individuals: community-dwelling older adults and physically active senior orienteering athletes, where the latter group has less gastrointestinal symptoms and a reported better well-being. With this approach, we explored if certain gut microbiota were related to healthy ageing. The participant data and faecal samples were collected from these two groups and the microbiota was whole-genome sequenced and taxonomically classified with MetaPhlAn. Results: The physically active senior orienteers had a more homogeneous microbiota within the group and a higher abundance of Faecalibacterium prausnitzii compared to the community-dwelling older adults. Faecalibacterium prausnitzii has previously shown to have beneficial properties. Senior orienteers also had a lower abundance of Parasutterella excrementihominis and Bilophila unclassified, which have been associated with impaired GI health. We could not observe any difference between the groups in terms of Shannon diversity index. Interestingly, a subgroup of community-dwelling older adults showed an atypical microbiota profile as well as the parameters for gastrointestinal symptoms and well-being closer to senior orienteers. Conclusions: Our results suggest specific composition characteristics of healthy microbiota in the elderly, and show that certain components of nutrition as well as psychological distress are not as tightly connected with composition or diversity variation in faecal microbiota samples.

Understanding gut microbiota in elderly's health will enable intervention through probiotics

2014 ◽  
Vol 5 (3) ◽  
pp. 235-246 ◽  
Author(s):  
G. Pérez Martínez ◽  
C. Bäuerl ◽  
M.C. Collado
Keyword(s):  
Gut Microbiota ◽  
Clinical Symptoms ◽  
Adaptive Immune Response ◽  
The Elderly ◽  
Research Field ◽  
Low Grade ◽  
Intestinal Microbes ◽  
Adaptive Immune ◽  
Age Related ◽  
Inflammatory State

Today, advances in the public health system of most countries have managed to extend notably life expectancy, however, elderly's health remain as a very serious concern. The lifelong stimulation of innate and adaptive immune systems leads to immunosenescence and, as result, to a low ability to produce immunoglobulins against pathogens but also to a low-grade chronic inflammatory state (inflammaging) that is linked to most age-related health problems, such as dementia, Alzheimer or atherosclerosis. This inflammatory state could make the host more sensitive to intestinal microbes, or vice versa, as changes in the gut microbiota composition are related to the progression of diseases and frailty in the elderly population. It was considered that gut microbiota changed during aging, with an increase of Bacteroidetes vs. Firmicutes proportion and a reduction of bifidobacterial counts, however recent studies reported a great inter-individual variation among elderly and a significant relationship between gut microbiota, diet and institution or community living. Intervention studies of probiotics and prebiotics in elderly are not very abundant, but most cases showed that Bifidobacterium populations can efficiently be stimulated with a concomitant decrease of Enterobacteria. Furthermore, also some studies demonstrated that probiotics decreased the synthesis of pro-inflammatory cytokines which are upregulated in the elderly, such as interleukin (IL)-8, IL-6 or tumour necrosis factor ?, among others, and they increased the levels of activated lymphocytes, natural killer cells, phagocytic activity and even showed a greater response to influenza vaccination. This suggests that direct manipulation of the gut microbiota may improve adaptive immune response and reduce inflammatory secretions, therefore compensating immunosenescence effects, however, there are no records of their effect on clinical symptoms or risk for disease. Those facts reveal that this is an open research field with very good scientific perspectives and above all they could bring likely improvements in the wellbeing of our seniors.

scholarly journals Metformin Improves Cognition by Reducing Leaky Gut and Benefiting Gut Microbiome–Goblet Cell–Mucin Axis

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 133-133
Author(s):  
Hariom Yadav ◽  
Shokouh Ahmadi ◽  
Bo Wang ◽  
Jamie Justice ◽  
Jingzhong Ding ◽  
...  
Keyword(s):  
Older Adults ◽  
Goblet Cell ◽  
Gut Microbiome ◽  
Cell Mass ◽  
Low Grade ◽  
Leaky Gut ◽  
Differentiation Markers ◽  
Mucin Production ◽  
Effective Strategies ◽  
Goblet Cell Differentiation

Abstract Older adults are suffering from several aging-related illnesses including cognitive decline and effective strategies to prevent and/or treat them are lacking, because of a poor understanding of therapeutic targets. Low-grade inflammation is a key risk factor of aging-related morbidities and mortalities, and it is often higher in older adults. Although, precise reasons for increased inflammation remain unknown, however, emerging evidence indicates that abnormal (dysbiotic) gut microbiome and dysfunctional gut permeability (leaky gut) are linked with increased inflammation in older adults. However, no drugs are available to treat aging-related microbiome dysbiosis and leaky gut, and little is known about the cellular and molecular processes that can be targeted to reduce leaky gut in older adults. Here, we demonstrated that metformin, a safe FDA approved antidiabetic drug, decreased leaky gut and inflammation in older obese mice, by beneficially modulating the gut microbiota. In addition, metformin increased goblet cell mass and mucin production in the older gut, thereby decreasing leaky gut and inflammation. Mechanistically, metformin increased the goblet cell differentiation markers by suppressing Wnt signaling. Our results suggest that metformin can prevent and treat aging-related leaky gut and inflammation, by beneficially modulating gut microbiome/goblet cell/mucin biology.

scholarly journals Mechanisms Linking the Gut-Muscle Axis With Muscle Protein Metabolism and Anabolic Resistance: Implications for Older Adults at Risk of Sarcopenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Konstantinos Prokopidis ◽  
Edward Chambers ◽  
Mary Ni Lochlainn ◽  
Oliver C. Witard
Keyword(s):  
Older Adults ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Gut Microbiota ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Low Grade ◽  
Anabolic Resistance ◽  
Amino Acid Availability ◽  
Low Grade Inflammation

Aging is associated with a decline in skeletal muscle mass and function—termed sarcopenia—as mediated, in part, by muscle anabolic resistance. This metabolic phenomenon describes the impaired response of muscle protein synthesis (MPS) to the provision of dietary amino acids and practice of resistance-based exercise. Recent observations highlight the gut-muscle axis as a physiological target for combatting anabolic resistance and reducing risk of sarcopenia. Experimental studies, primarily conducted in animal models of aging, suggest a mechanistic link between the gut microbiota and muscle atrophy, mediated via the modulation of systemic amino acid availability and low-grade inflammation that are both physiological factors known to underpin anabolic resistance. Moreover, in vivo and in vitro studies demonstrate the action of specific gut bacteria (Lactobacillus and Bifidobacterium) to increase systemic amino acid availability and elicit an anti-inflammatory response in the intestinal lumen. Prospective lifestyle approaches that target the gut-muscle axis have recently been examined in the context of mitigating sarcopenia risk. These approaches include increasing dietary fiber intake that promotes the growth and development of gut bacteria, thus enhancing the production of short-chain fatty acids (SCFA) (acetate, propionate, and butyrate). Prebiotic/probiotic/symbiotic supplementation also generates SCFA and may mitigate low-grade inflammation in older adults via modulation of the gut microbiota. Preliminary evidence also highlights the role of exercise in increasing the production of SCFA. Accordingly, lifestyle approaches that combine diets rich in fiber and probiotic supplementation with exercise training may serve to produce SCFA and increase microbial diversity, and thus may target the gut-muscle axis in mitigating anabolic resistance in older adults. Future mechanistic studies are warranted to establish the direct physiological action of distinct gut microbiota phenotypes on amino acid utilization and the postprandial stimulation of muscle protein synthesis in older adults.

scholarly journals Aging, Gut Microbiota and Metabolic Diseases: Management through Physical Exercise and Nutritional Interventions

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 16
Author(s):  
María Juárez-Fernández ◽  
David Porras ◽  
María Victoria García-Mediavilla ◽  
Sara Román-Sagüillo ◽  
Javier González-Gallego ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Gut Microbiota ◽  
Healthy Aging ◽  
Metabolic Diseases ◽  
The Elderly ◽  
Low Grade ◽  
Mortality And Morbidity ◽  
Nutritional Interventions ◽  
Global Epidemic ◽  
Physiological Homeostasis

Gut microbiota (GM) is involved in the maintenance of physiological homeostasis, thus the alteration of its composition and functionality has been associated with many pathologies such as metabolic diseases, and could also be linked with the progressive degenerative process in aging. Nowadays, life expectancy is continuously rising, so the number of elder people and the consequent related pathologies demand new strategies to achieve healthy aging. Besides, actual lifestyle patterns make metabolic diseases a global epidemic with increasing trends, responsible for a large mortality and morbidity in adulthood and also compromising the health status of later stages of life. Metabolic diseases and aging share a profile of low-grade inflammation and innate immunity activation, which may have disturbances of GM composition as the leading mechanism. Thus, GM emerges as a therapeutic target with a double impact in the elderly, counteracting both aging itself and the frequent metabolic diseases in this population. This review summarizes the role and compositional changes of the GM in aging and its modulation through nutritional interventions and physical exercise as a strategy to counteract the aging process and the related metabolic diseases.

scholarly journals Effects of Litchi on Systemic Low-Grade Inflammation and the Structure and Function of Gut Microbiota in HFA Mice

2020 ◽  
Author(s):  
Dongfang Sun ◽  
Chen Wang ◽  
Lijun Sun ◽  
Lianhua Hu ◽  
Yaling Wang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Gut Microbiota ◽  
Dose Group ◽  
Cell Junction ◽  
Mucosal Barrier ◽  
High Dose ◽  
Low Grade ◽  
Healthy Human ◽  
Intestinal Mucosal Barrier ◽  
Low Grade Inflammation

Abstract Background: Certain foods are known as “heating” foods in Chinese medicine as over consumption of them can lead to symptoms known as “heating up”, which have been shown to be symptoms of systemic low-grade inflammation. However, the mechanism by which these foods cause inflammation is not clear. In this study, we investigated dysbacteriosis of gut microbiota as a possible cause of inflammation by litchi, a typical “heating” food. Human flora-associated (HFA) mice model was constructed by first sterilizing their guts by oral administration of antibiotics, and then transplantation of fecal microbial suspension from a healthy human adult. After gavaging the mice with litchi powder suspension at low, medium and high doses (400, 800, 1600 mg/kg·d-1 respectively) for 7 days, the serum level of inflammatory cytokines, gut microbiota and the integrity of intestinal mucosal barrier were measured.Result: The intervention of litchi significantly increased the diversity of mice gut flora. The ratio of Bacteroidetes/Firmicutes and the abundance of Actinobacteria increased significantly. At the genus level, the abundance of Phascolarctobacterium, Akkermansia, Megasomonas and Lactobacillus generally decreased, while the abundance of Prevotella and Bacteroides increased significantly, especially in the high litchi dose group. The abundance of Bilophila increased significantly only in high dose group. litchi intervention caused serum TNF-α level to increase by more than two times and LPS level to double, but a decrease in IL-1β and IL-6 levels. Medium and high dose litchi intervention caused a widening of intestinal epithelial cell junction complex, and general weakening of the intestinal mucosal barrier as well as reduced efficiency of gut microbiota in energy conversion. Conclusion: This study confirmed the notion in Chinese medicine that as a “heating” food, litchi when consumed excessively can lead to low degree systematic inflammation and demonstrated that this is linked to its ability to cause dysbacteriosis of the gut microbiota and weakening of the intestinal mucosal tissues.

scholarly journals Leukocyte count, systemic inflammation, and health status in older adults: a narrative review

2018 ◽  
Vol 81 (1) ◽  
pp. 81-101 ◽  
Author(s):  
Piotr Chmielewski
Keyword(s):  
Older Adults ◽  
Systemic Inflammation ◽  
Molecular Mechanisms ◽  
Leukocyte Count ◽  
The Elderly ◽  
Low Grade ◽  
Associated Diseases ◽  
Increased Risk ◽  
Leukocyte Counts ◽  
Normal Leukocyte

Abstract Epidemiological and clinical studies suggest that elevated leukocyte count within the normal range can predict cardiovascular and total mortality in older adults. These findings are remarkable because this simple and common laboratory test is included in routine medical check-ups. It is well known that chronic systemic inflammation (inflammaging) is one of the hallmarks of aging and an important component of obesity-associated insulin resistance that can lead to type 2 diabetes and other health problems in both overweight individuals and elderly people. To understand the molecular mechanisms linking increased systemic inflammation with aging-associated diseases and elevated leukocyte counts in the elderly is to unravel the multiplicity of molecular factors and mechanisms involved in chronic low-grade systemic inflammation, the gradual accumulation of random molecular damage, age-related diseases, and the process of leukopoiesis. There are several possible mechanisms through which chronic low-grade systemic inflammation is associated with both higher leukocyte count and a greater risk of aging-associated conditions in older adults. For example, the IL-6 centric model predicts that this biomediator is involved in chronic systemic inflammation and leukopoiesis, thereby suggesting that elevated leukocyte count is a signal of poor health in older adults. Alternatively, an increase in neutrophil and monocyte counts can be a direct cause of cardiovascular events in the elderly. Interestingly, some authors assert that the predictive ability of elevated leukocyte counts with regard to cardiovascular and allcause mortality among older adults surpass the predictive value of total cholesterol. This review reports the recent findings on the links between elevated but normal leukocyte counts and the increased risks of all-cause, cardiovascular, and cancer mortality. The possible molecular mechanisms linking higher but normal leukocyte counts with increased risk of aging-associated diseases in the elderly are discussed here.

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