Nutrient load acts as a driver of gut microbiota load, community composition and metabolic functionality in the simulator of the human intestinal microbial ecosystem

ABSTRACT A recently introduced quantitative framework for gut microbiota analysis indicated that microbial load alterations can be linked to various diseases, making it essential to pinpoint its determinants. We identified nutrient load as a main driver of the quantitative microbial community composition and functionality in vitro by stepwise decreasing standardized feed concentrations from 100% to 33%, 20% and 10% in 5-day intervals. While the proportional composition and metabolic profile were mainly determined by the inter-individual variability (35% and 41%), nutrient load accounted for 58%, 23% and 65% of the observed variation in the microbial load, quantitative composition and net daily metabolite production, respectively. After the 10-fold nutrient reduction, the microbial load decreased by 79.72 ± 9% and 82.96 ± 1.66% in the proximal and distal colon, respectively, while the net total short-chain fatty acid production dropped by 79.42 ± 4.42% and 84.58 ± 2.42%, respectively. The majority of microbial taxa quantitatively decreased, whereas a select group of nutritional specialists, such as Akkermansia muciniphila and Bilophila wadsworthia, and a number of opportunistic pathogens remained unaffected. This shows that nutrient load is an important driver of the human gut microbiome and should be considered in future in vitro and in vivo dietary research. This study, performed in an advanced in vitro gastrointestinal model, identified nutrient load as an important driver of the gut microbial load, quantitative gut microbiome composition and metabolic functionality.