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

Abstract

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.

In vivo screening of multiple bacterial strains identifies Lactobacillus rhamnosus Lb102 and Bifidobacterium animalis ssp. lactis Bf141 as probiotics that improve metabolic disorders in a mouse model of obesity

“…More profound changes in the gut microbiota composition may occur after administration of multiple probiotic strains, combined or not with prebiotics, as previously shown for the VSL#3 cocktail that contains 8 different strains (15). Nagpal et al (59) also recently reported that a new cocktail of 10 humanorigin lactic acid bacteria modulates gut microbiota composition within a few hours and up to 10 d, which was accompanied by the increase of SCFA production. The authors used a dose of 10 11 cfu/gavage, whereas in the current study, a dose of 10 9 cfu/gavage has been used, suggesting that differences in gut microbiota modulations between both studies could be related to the dose.…”

“…Nagpal et al . (59) also recently reported that a new cocktail of 10 human‐origin lactic acid bacteria modulates gut microbiota composition within a few hours and up to 10 d, which was accompanied by the increase of SCFA production. The authors used a dose of 10 11 cfu/gavage, whereas in the current study, a dose of 10 9 cfu/gavage has been used, suggesting that differences in gut microbiota modulations between both studies could be related to the dose.…”

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

“…Fan et al observed that bacteroides including Blautia producta and Bacteroides thetaiotaomicron directly affect C. albicans colonization through SCFAs 2 . Our recent studies found that the probiotics interventions increase the SCFAs production by modulating human and mice gut microbiome 92 . Therefore, future studies including characterization of probiotic or commensal bacteria to enhance the abundance of SCFA levels may form a novel approach to prevent and treat C. albicans colonization and subsequent pathogenesis.…”

“…Equal amount of snap frozen cecal content was weighed, dissolved in HPLC grade water and supernatants were collected after centrifugation (12,000 g, 10 min), while processing on ice. Concentrations of SCFAs (acetate, propionate and butyrate) were determined using a HPLC system (Waters-2695 Alliance HPLC system, Waters Corporation, Milford, MA, USA) equipped with Aminex HPX-87H column (Bio-Rad Laboratories, Hercules, CA) and DAD detector (210 nm), and eluting with H 2 SO 4 (0.005 N) mobile phase with a flow rate of 0.6 ml/min at 25°C, as described elsewhere 92 .…”

A Novel Index for Predicting Health Status Using Species-level Gut Microbiome Profiling

“…In this regard, we anticipate the emerging scenario wherein GMHI could aid the proper selection of healthy donors and stool samples. To this point, GMHI could further facilitate future efforts to define design-principles of a healthy gut microbiome and to establish rational strategies for restoring or maintaining wellness in the form of probiotic 'cocktail' communities 68,69 .…”