AM. Highprotein diet modifies colonic microbiota and luminal environment but not colonocyte metabolism in the rat model: the increased luminal bulk connection. Am J Physiol Gastrointest Liver Physiol 307: G459-G470, 2014. First published June 26, 2014; doi:10.1152/ajpgi.00400.2013.-High-protein diets are used for body weight reduction, but consequences on the large intestine ecosystem are poorly known. Here, rats were fed for 15 days with either a normoproteic diet (NP, 14% protein) or a hyperproteichypoglucidic isocaloric diet (HP, 53% protein). Cecum and colon were recovered for analysis. Short-and branched-chain fatty acids, as well as lactate, succinate, formate, and ethanol contents, were markedly increased in the colonic luminal contents of HP rats (P Ͻ 0.05 or less) but to a lower extent in the cecal luminal content. This was associated with reduced concentrations of the Clostridium coccoides and C. leptum groups and Faecalibacterium prausnitzii in both the cecum and colon (P Ͻ 0.05 or less). In addition, the microbiota diversity was found to be higher in the cecum of HP rats but was lower in the colon compared with NP rats. In HP rats, the colonic and cecal luminal content weights were markedly higher than in NP rats (P Ͻ 0.001), resulting in similar butyrate, acetate, and propionate concentrations. Accordingly, the expression of monocarboxylate transporter 1 and sodium monocarboxylate transporter 1 (which is increased by higher butyrate concentration) as well as the colonocyte capacity for butyrate oxidation were not modified by the HP diet, whereas the amount of butyrate in feces was increased (P Ͻ 0.01). It is concluded that an increased bulk in the large intestine content following HP diet consumption allows maintenance in the luminal butyrate concentration and thus its metabolism in colonocytes despite modified microbiota composition and increased substrate availability.protein; microbiota; SCFA; transport; metabolism HIGH-PROTEIN (HP) diets are commonly used for body weight loss (36,38). In fact, such diets have been shown to increase satiety, to modify lipid metabolism, and to facilitate short-and middle-term weight reduction (24,61,72). However, the consequences on gut microbiota composition, on microbial-derived metabolites in the large intestine luminal content, and on colonocyte epithelial cell metabolic capacities have been little studied.Increasing protein intake induces an increase in the proportion of nitrogenous compounds, mainly protein, peptides, and to a lesser extent amino acids, entering the large intestine (13,23,25,51,64). They are subjected to luminal proteolysis and subsequent metabolism by the large number of microorganisms of the large intestine microbiota (about 10 11 to 10 12 viable bacteria/g content) (29) leading to the production of numerous amino acid-derived metabolites (53), including phenols, indoles, amines, sulfide, ammonia, and monocarboxylic acids. Monocarboxylic acids include short-chain fatty acids (SCFA), branched-chain fatty acids (BCFA) and several other organ...