Quantity and source of dietary protein influence metabolite production by gut microbiota and rectal mucosa gene expression: a randomized, parallel, double-blind trial in overweight humans

Abstract

Although high-protein diets (HPDs) are frequently consumed for body-weight control, little is known about the consequences for gut microbiota composition and metabolic activity and for large intestine mucosal homeostasis. Moreover, the effects of HPDs according to the source of protein need to be considered in this context. The objective of this study was to evaluate the effects of the quantity and source of dietary protein on microbiota composition, bacterial metabolite production, and consequences for the large intestinal mucosa in humans. A randomized, double-blind, parallel-design trial was conducted in 38 overweight individuals who received a 3-wk isocaloric supplementation with casein, soy protein, or maltodextrin as a control. Fecal and rectal biopsy-associated microbiota composition was analyzed by 16S ribosomal DNA sequencing. Fecal, urinary, and plasma metabolomes were assessed by H-nuclear magnetic resonance. Mucosal transcriptome in rectal biopsies was determined with the use of microarrays. HPDs did not alter the microbiota composition, but induced a shift in bacterial metabolism toward amino acid degradation with different metabolite profiles according to the protein source. Correlation analysis identified new potential bacterial taxa involved in amino acid degradation. Fecal water cytotoxicity was not modified by HPDs, but was associated with a specific microbiota and bacterial metabolite profile. Casein and soy protein HPDs did not induce inflammation, but differentially modified the expression of genes playing key roles in homeostatic processes in rectal mucosa, such as cell cycle or cell death. This human intervention study shows that the quantity and source of dietary proteins act as regulators of gut microbiota metabolite production and host gene expression in the rectal mucosa, raising new questions on the impact of HPDs on the large intestine mucosa homeostasis. This trial was registered at clinicaltrials.gov as NCT02351297.

Gut Microbial, Inflammatory and Metabolic Signatures in Older People with Physical Frailty and Sarcopenia: Results from the BIOSPHERE Study

“…Indeed, diet influences gut microbiota composition and functionality, which may ultimately impact skeletal muscle. While high protein intake has been endorsed as a strategy against sarcopenia [54], protein-enriched diets may shift bacterial metabolism towards AA degradation and fermentation [55]. Hence, the role of gut microbes as transducers of nutrient signaling to the host implies the need of monitoring the composition and function of gut microbiota during nutritional interventions for sarcopenia.…”

The gut microbiota metabolite indole alleviates liver inflammation in mice

“…In contrast, some dietary proteins escape the small intestine (<10%) (57) and might be an important source of exogenous tryptophan for the microbiota (17). Indeed, in humans, high-protein diets increase indole production by the microbiota, as shown by an increase in I3S urinary excretion (58). However, increasing dietary protein intake lacks specificity because it also increases the production of many other amino acid–derived bacterial metabolites.…”

The Effect of Lean‐Seafood and Non‐Seafood Diets on Fecal Metabolites and Gut Microbiome: Results from a Randomized Crossover Intervention Study

“…Beaumont et al. recently investigated the effect of quantity and type of dietary protein on the gut metabolite production, and they observed a shift toward amino acid metabolism upon ingestion of high protein diets with casein and soy protein . However, Beaumont et al.…”