Strain-level variation controls nutrient niche occupancy by health-associated <i>Anaerostipes hadrus</i>

Nutrient niche access by the gut microbiota impacts community assembly and dynamics, the production of host-benefiting short-chain fatty acids (SCFAs), and pathogen inhibition through colonization resistance. Furthermore, deciphering if and how niche access varies on a strain level will be important as individual strains of gut microbes are selected for inclusion in new live biotherapeutic products. Despite this, for many gut anaerobes, nutrient niche occupancy and impacts of strain variation remain unknown. Here, we examined nutrient niches of <i>Anaerostipes hadrus</i> (AH)<i>,</i> a butyrate-producing member of the <i>Lachnospiraceae</i> family. We found that AH isolates encode a carbohydrate metabolism gene repertoire that is distinct from other <i>Lachnospiraceae</i>. Furthermore, tested AH isolates show variation in carbohydrate-related genes between strains and large numbers of genes associated with horizontal gene transfer events. Functionally, we demonstrate that AH isolates exhibit strain-specific patterns of nutrient niche access that can be associated with the gain, loss, and disruption of gene clusters enabling specific carbohydrate metabolism. This strain-specific carbohydrate use drives variable SCFA production. Unexpectedly, strains exhibit differential preferences for carbohydrates, which alter SCFA profiles in environments with multiple possible nutrient niches available. Furthermore, when strains of AH interact in an environment with multiple nutrient niches available, strain-strain interactions result in varying SCFA profiles that extend beyond the additive effects of individual strain behavior. Altogether, these results demonstrate the importance of evaluating strain-level variation in the design of future live biotherapeutic products.