Amino acid auxotrophies in human gut bacteria are linked to higher microbiome diversity and long-term stability

Abstract

Amino acid auxotrophies are prevalent among bacteria. They can govern ecological dynamics in microbial communities and indicate metabolic cross-feeding interactions among coexisting genotypes. Despite the ecological importance of auxotrophies, their distribution and impact on the diversity and function of the human gut microbiome remain poorly understood. This study performed the first systematic analysis of the distribution of amino acid auxotrophies in the human gut microbiome using a combined metabolomic, metagenomic, and metabolic modeling approach. Results showed that amino acid auxotrophies are ubiquitous in the colon microbiome, with tryptophan auxotrophy being the most common. Auxotrophy frequencies were found to be higher for those amino acids, that are also essential to the human host. Moreover, a higher overall abundance of auxotrophies was associated with greater microbiome diversity and stability, and the distribution of auxotrophs was found to be related to the human host's metabolome, including trimethylamine oxide, small aromatic acids, and secondary bile acids. Thus, our results suggest that amino acid auxotrophies are important factors that contribute to microbiome ecology and host-microbiome metabolic interactions.

Impact of Dietary Macromolecular Quantity and Quality on Host Assimilation of Microbially Derived Essential Amino Acids

“…For example, certain microbial groups were involved in the synthesis of a speci c set of AA ESS , suggesting cross-feeding of AA ESS between different members of the gut microbiota in response to dietary protein content. Our results are consistent with recent studies highlighting how AA auxotrophic gut bacteria can in uence gut microbiome dynamics (such as diversity and long-term stability) through the creation of niches for different microbial groups to occupy via metabolite cross-feeding [23]. Therefore, microbial groups capable of synthesizing subsets of AA ESS are likely responsible for the provisioning of AA ESS to not only other gut microbial members, but also to their mammalian hosts.…”

“…Our estimates of the relative proportion of microbial AA ESS used to synthesize mice muscle tissue are likely underestimates because they only consider the contribution of AA ESS synthesized de novo from dietary carbohydrates. However, gut microbes can synthesize AA ESS from a diverse pool of metabolite precursors, including non-essential AA, and therefore likely contribute even more microbially synthesized AA ESS to their host than reported here [23]. It should also be noted that microbial AA ESS d 13 C values were estimated using carbon isotope data for dietary carbohydrates and isotopic fractionation factors for bacteria grown on a sole carbon source [74,75].…”

“…Another bacterial family, Lachnospiraceae (Phylum Bacillota), differentially abundant in mice fed the low protein synthetic diet (Fig. 3; SI [23,110,115] and have the ability to synthesize all of these AA ESS [116].…”

“…In contrast, mice heavily relied on their intestinal microbes for AA ESS to build muscle regardless of protein treatment when fed more complex dietary substrates in the semi-natural diet. Further, complex nutritional environments appear to select for AA auxotrophic microbial communities by creating niches for different groups to occupy through metabolite cross-feeding [23]. Lastly, our estimates for microbial contribution of AA ESS to host muscle are likely conservative because they only include values from microbes synthesizing AA ESS from carbohydrate precursors.…”

“…Several sources of nitrogen are available for gut microbial AA synthesis including ammonia, urea, dietary-, host-, and microbially-derived AA, while carbohydrate fermentation provides a substantial pool of carbon precursors, namely acetate, carbon dioxide (CO 2 ), and to a lesser degree, propionate [13,20,22]. Recent evidence supports complex gut microbial community dynamics in which different microbial groups synthesize certain AA and participate in cross-feeding in which compounds produced by one bacterial taxon are further metabolized by other microbial groups [23]. The extent of AA cross-feeding among gut microbes is unknown, however, it is likely in uenced by their immediate nutritional environment and substrate availability.…”