Underfeeding and oral vancomycin perturb the human gut microbiome and impair nutrient absorption

Studies in mice and humans have indicated that the trillions of microorganisms within the gastrointestinal tract (the gut microbiome) may impact nutrient absorption but direct evidence in humans is lacking. To address this knowledge gap, we conducted a two-phase extended inpatient study in which we directly measured stool calorie loss, a reflection of absorbed nutrients, during dietary (under versus overfeeding) and pharmacologic (oral vancomycin versus placebo) interventions intended to alter the gut microbiome. Food and stool calories were measured by bomb calorimetry. Percent calorie loss was calculated (stool calories/ingested calories) x100. Both interventions (underfeeding and vancomycin treatment) led to greater percent stool calorie loss (indicating decreased nutrient absorption) accompanied by an expansion of Akkermansia muciniphila. Vancomycin also induced further widespread alterations in the gut microbiome structure decreasing gut microbial diversity and changing the relative abundance of all major phyla. The magnitude of the difference in percent calorie loss was similar in the two interventions and both were accompanied by decreased circulating concentrations of butyrate, a short-chain fatty acid which is one of the major end products of microbial metabolism representing a reduction in the availability or processing of nutrients. Interventions that alter energy availability to the gut microbiome either via calorie reduction or by widespread alteration of the microbiome structure increase stool energy loss indicating role for the normal human gut microbiome in the efficiency of nutrient harvest.