The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon

Abstract

SUMMARY The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metabolism in a general versus tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially-produced butyrate as their primary energy source. Colonocytes from germfree mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD+, oxidative phosphorylation, and ATP levels, which results in AMPK activation, p27kip1 phosphorylation, and autophagy. When butyrate is added to germfree colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy. The mechanism is due to butyrate acting as an energy source rather than as an HDAC inhibitor.

Habitat degradation impacts black howler monkey (Alouatta pigra) gastrointestinal microbiomes

“…Butyrate is the primary energy source for the colonic epithelium and is recognized for numerous health-promoting benefits (Donohoe et al, 2011;Grootaert et al, 2011;Hu et al, 2010;Rawluszko et al, 2011;Sharma and Singh, 2011). Butyrateproducing taxa, such as Butyrivibrio spp.…”

Le microbiote intestinal et la digestion des polysaccharides

“…Ce produit constitue la première source d'énergie pour les cellules du côlon (colonocytes), et son manque provoque l'autophagie ou l'autolyse de ces dernières qui finissent par se dégrader [22]. On attribue aux SCFA une multitude de fonctions bénéfiques, telles que l'inhibition de la prolifération des cellules tumorales du côlon et la stimulation de la croissance de colonocytes sains [23].…”

Energy, Oxidative Stress, and Inflammation in the Colon

“…Clinical trials utilizing SCFA enemas to treat diversion colitis have been limited and inconclusive. Thus, because SCFA enemas are not used routinely to treat diversion colitis, surgical restoration of bowel continuity is definitive [5].Butyrate regulation of energy metabolism in colonocytes has been studied in germfree (GF) mice [6]. Similar to humans, mouse colonocytes utilize bacterially-produced butyrate as their primary energy source.…”

“…Butyrate regulation of energy metabolism in colonocytes has been studied in germfree (GF) mice [6]. Similar to humans, mouse colonocytes utilize bacterially-produced butyrate as their primary energy source.…”

“…Nutrient-deficient and energy-deficient colonocytes will experience alterations in their redox state and decreased cellular oxidative phosphorylation with resultant increase in oxidative stress. In an effort to maintain energy homeostasis and cellular integrity, colonocytes in GF mice degrade cellular proteins and damaged organelles to generate amino acids for energy consumption in a process termed autophagy [6]. Addition of butyrate to GF colonocytes partially restores mitochondrial respiration and prevents autophagy.…”