Metagenomic analysis reveals distinct patterns of gut lactobacillus prevalence, abundance, and geographical variation in health and disease

Lactobacilli are exploited extensively for food fermentation and biotechnology. Some food and gut isolates have been developed as probiotics, for which species that may be commensal to the human host are considered desirable. However, the robustness of defining original niches for lactobacilli – food, environment, the gut – is questionable, and culture-independent analyses of prevalence in different human populations is lacking. Here we analyzed the abundance of lactobacilli in 6,154 subjects from a database of highly curated fecal shotgun metagenomics data spanning 25 nationalities, with ages ranging from infancy to 102 years. Twenty-five species were detected, which we assigned into low, medium, and high prevalence groups. The microbiome of apparently healthy individuals could be categorized into 6 clusters or Lactobacillotypes (LbTypes), with three of the Lbtypes being dominated by L. delbrueckii, L. ruminis, L. casei, and the other three comprising a combination of different species. These Lactobacillus clusters exhibit distinct global abundance patterns. The cluster prevalences also display distinct age-specific trends influenced by geography, with overall lactobacillus prevalence increasing significantly with age in North America and Europe but declining with age in non-Westernized societies. Regression analysis stratified by regional location identified distinct associations of the Lactobacillotypes with age, BMI, and gender. Cirrhosis, fatty-liver, , IBD and T2D were characterized by net gain of lactobacilli, whereas hypertension patients harbored depleted lactobacillus levels. Collectively these data indicate that the species abundance of gut lactobacilli is moderated by geography, diet, and interaction with the whole microbiome, and has strong interactions with diseases associated with a western lifestyle.