Hariom Yadav

Probiotics Mediated Modulation of Gut-Flora Might Be a Biotherapeutical Approach for Obesity and Type 2 Diabetes

these evidences doesn’t exclude the differential efficacy of probiotics in human subjects, hence very well controlled/ designed studies are urgently needed to check the efficacy of probiotics in human health against obesity and diabetes. A deeper knowledge of our gut ecology will be mandatory in the hope to target much more specific probiotic intervention. In this regards it is of interest the recent intriguing review from Rastmanesh [13] suggesting that a high-polyphenol and selectively-restricted probiotic diet could represent a novel strategy for planning a successful dietary regimen and/or neutraceutical/ pharmaceutical preparations to achieve and maintain a normal body weight in obese individuals. Overall, such studies will also give opportunities to industries to think about the risk vs safety of probiotic formulations for obesity and diabetes in consumers, worldwide.

Gut Microbiome Composition in Non-human Primates Consuming a Western or Mediterranean Diet

The mammalian gastrointestinal tract harbors a highly diverse and dynamic community of bacteria. The array of this gut bacterial community, which functions collectively as a fully unified organ in the host metabolism, varies greatly among different host species and can be shaped by long-term nutritional interventions. Non-human primates, our close phylogenetic relatives and ancestors, provide an excellent model for studying diet-microbiome interaction; however, compared to clinical and rodent studies, research targeting primate gut microbiome has been limited. Herein, we analyze the gut microbiome composition in female cynomolgus macaques (Macaca fascicularis; n = 20) after the long-term (2.5 years) consumption of diets designed to mimic recent human Western- (WD; n = 10) or Mediterranean-type (MD; n = 10) diets. Microbiome diversity in MD consumers was significantly higher by the Shannon diversity index compared to the WD consumers, with similar but non-significant trends noted for the diversity metrics of species richness (Chao 1), observed operational taxonomic units (OTUs) and phylogenetic diversity (PD) whole Tree. Compared to the MD, the WD group demonstrated a higher Firmicutes-Bacteroides ratio and a significantly higher abundance of families Clostridiacea and Lactobacillaceae. Further analyses reveal significantly higher abundance of genera Lactobacillus, Clostridium, Faecalibacterium, and Oscillospira and lower abundance of Ruminococcus and Coprococcus in MD consumers relative to WD consumers. OTUs belonging to several species also show significant differences between the two groups, with Lactobacillus species demonstrating a prominently higher abundance in the MD consumers. The data reveal several differences in the gut microbiome of primates consuming the two different diets and should be useful for further studies aimed at understanding the diet-microbiome-health interactions in primates.

Gut microbiome and aging: Physiological and mechanistic insights

The development of human gut microbiota begins as soon as the neonate leaves the protective environment of the uterus (or maybe in-utero) and is exposed to innumerable microorganisms from the mother as well as the surrounding environment. Concurrently, the host responses to these microbes during early life manifest during the development of an otherwise hitherto immature immune system. The human gut microbiome, which comprises an extremely diverse and complex community of microorganisms inhabiting the intestinal tract, keeps on fluctuating during different stages of life. While these deviations are largely natural, inevitable and benign, recent studies show that unsolicited perturbations in gut microbiota configuration could have strong impact on several features of host health and disease. Our microbiota undergoes the most prominent deviations during infancy and old age and, interestingly, our immune health is also in its weakest and most unstable state during these two critical stages of life, indicating that our microbiota and health develop and age hand-in-hand. However, the mechanisms underlying these interactions are only now beginning to be revealed. The present review summarizes the evidences related to the age-associated changes in intestinal microbiota and vice-versa, mechanisms involved in this bi-directional relationship, and the prospective for development of microbiota-based interventions such as probiotics for healthy aging.

Antibiotic-induced decreases in the levels of microbial-derived short-chain fatty acids promote gastrointestinal colonization of Candida albicans

Candida albicans is the fourth most common cause of systemic nosocomial infections, posing a significant risk in immunocompromised individuals. As the majority of systemic C. albicans infections stem from endogenous gastrointestinal (GI) colonization, understanding the mechanisms associated with GI colonization is essential in the development of novel methods to prevent C. albicans-related mortality. In this study, we investigated the role of microbial-derived short-chain fatty acids (SCFAs) including acetate, butyrate, and propionate on growth, morphogenesis, and GI colonization of C. albicans. Our results indicate that cefoperazone-treated mice susceptible to C. albicans infection had significantly decreased levels of SCFAs in the cecal contents that correlate with a higher fungal load in the feces. Further, using in vivo concentration of SCFAs, we demonstrated that SCFAs inhibit the growth, germ tube, hyphae and biofilm development of C. albicans in vitro. Collectively, results from this study demonstrate that antibiotic-induced decreases in the levels of SCFAs in the cecum enhances the growth and GI colonization of C. albicans.

Human-origin probiotic cocktail increases short-chain fatty acid production via modulation of mice and human gut microbiome

The gut bacteria producing metabolites like short-chain fatty acids (SCFAs; e.g., acetate, propionate and butyrate), are frequently reduced in Patients with diabetes, obesity, autoimmune disorders, and cancers. Hence, microbiome modulators such as probiotics may be helpful in maintaining or even restoring normal gut microbiome composition to benefit host health. Herein, we developed a human-origin probiotic cocktail with the ability to modulate gut microbiota to increase native SCFA production. Following a robust protocol of isolation, characterization and safety validation of infant gut-origin Lactobacillus and Enterococcus strains with probiotic attributes (tolerance to simulated gastric and intestinal conditions, adherence to intestinal epithelial cells, absence of potential virulence genes, cell-surface hydrophobicity, and susceptibility to common antibiotics), we select 10 strains (5 from each genera) out of total 321 isolates. A single dose (oral gavage) as well as 5 consecutive doses of this 10-strain probiotic cocktail in mice modulates gut microbiome and increases SCFA production (particularly propionate and butyrate). Inoculation of these probiotics in human feces also increases SCFA production along with microbiome modulation. Results indicate that human-origin probiotic lactobacilli and enterococci could ameliorate gut microbiome dysbiosis and hence may prove to be a potential therapy for diseases involving reduced SCFAs production in the gut.

Obesity-Linked Gut Microbiome Dysbiosis Associated with Derangements in Gut Permeability and Intestinal Cellular Homeostasis Independent of Diet

This study aimed to determine the association between non-high-fat diet-induced obesity- (non-DIO-) associated gut microbiome dysbiosis with gut abnormalities like cellular turnover of intestinal cells, tight junctions, and mucin formation that can impact gut permeability. We used leptin-deficient (Lepob/ob) mice in comparison to C57BL/6J control mice, which are fed on identical diets, and performed comparative and correlative analyses of gut microbiome composition, gut permeability, intestinal structural changes, tight junction-mucin formation, cellular turnover, and stemness genes. We found that obesity impacted cellular turnover of the intestine with increased cell death and cell survival/proliferation gene expression with enhanced stemness, which are associated with increased intestinal permeability, changes in villi/crypt length, and decreased expression of tight junctions and mucus synthesis genes along with dysbiotic gut microbiome signature. Obesity-induced gut microbiome dysbiosis is also associated with abnormal intestinal organoid formation characterized with decreased budding and higher stemness. Results suggest that non-DIO-associated gut microbiome dysbiosis is associated with changes in the intestinal cell death versus cell proliferation homeostasis and functions to control tight junctions and mucous synthesis-regulating gut permeability.