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

Ravinder Nagpal,Thomas Becton,Shaohua Wang,Russel Read,Dalane W Kitzman,Jason Gagliano,Hariom Yadav,Sargurunathan Subashchandrabose,Shokouh Ahmadi,Joshua Hayes

doi:10.1038/s41598-018-30114-4

Ravinder Nagpal, Thomas Becton + Show 8 more

Open Access

https://doi.org/10.1038/s41598-018-30114-4

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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.

Highlights

IntroductionThe human gastrointestinal tract harbors a highly diverse and complex community of 1013 to 1014 microorganisms (collectively known as the gut microbiome) living in a symbiotic manner[1]
The human gastrointestinal tract harbors a highly diverse and complex community of 1013 to 1014 microorganisms living in a symbiotic manner[1]
We develop a consortium of 10 probiotic Lactobacillus and Enterococcus strains isolated from healthy infants’ gut, and demonstrate their effects on the gut microbiome composition and SCFAs levels in-vivo in healthy mice as well as ex-vivo in human feces

Summary

Introduction

The human gastrointestinal tract harbors a highly diverse and complex community of 1013 to 1014 microorganisms (collectively known as the gut microbiome) living in a symbiotic manner[1]. Specific probiotic strains can effectively prevent or treat diseases including inflammatory bowel disease[17], necrotizing enterocolitis[18], obesity/type 2 diabetes[19], and autoimmunity[20] in both rodent models and humans; the mechanisms underlying such benefits are not understood These reports have led to an extensive demand for probiotic supplements over the last decade, thereby prompting a massive increase in the development of new probiotic products for the consumer market. Probiotics are rapidly emerging as novel and natural therapeutic options; isolation and characterization of new strains with well-characterized mechanisms of action remain of considerable interest and importance In this context, we develop a consortium of 10 probiotic Lactobacillus and Enterococcus strains isolated from healthy infants’ gut, and demonstrate their effects on the gut microbiome composition and SCFAs levels in-vivo in healthy mice as well as ex-vivo in human feces

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