Nutrient acquisition strategies by gut microbes

Abstract

The composition and function of the gut microbiota are intimately tied to nutrient acquisition strategies and metabolism, with significant implications for host health. Both dietary and host-intrinsic factors influence community structure and the basic modes of bacterial energy metabolism. The intestinal tract is rich in carbon and nitrogen sources; however, limited access to oxygen restricts energy-generating reactions to fermentation. By contrast, increased availability of electron acceptors during episodes of intestinal inflammation results in phylum-level changes in gut microbiota composition, suggesting that bacterial energy metabolism is a key driver of gut microbiota function. In this review article, we will illustrate diverse examples of microbial nutrient acquisition strategies in the context of habitat filters and anatomical location and the central role of energy metabolism in shaping metabolic strategies to support bacterial growth in the mammalian gut.

Keywords: bacterial metabolism; fermentation; gut microbiota; respiration.

Figure 1:. Diet and host factors (habitat filters) dictate metabolism of the gut microbiota.

Bile acids, antimicrobial peptides, pH, and mucus production, influence microbial community structure in the small intestine. In the anaerobic colon, poorly absorbed dietary polysaccharides are fermented; the fermentation product butyrate instructs the intestinal epithelium to perform β-oxidation, thus limiting oxygen diffusion into the gut and creating an anaerobic environment. Created with BioRender.com.

Figure 2:. Schematic representation of the starch utilization system (SUS) in B. thetaiotaomicron.

Starch molecules are bound by outer membrane (OM)-associated lipoproteins such as SusD, SusE, and SusF. The glycoside hydrolase SusG generates oligosaccharides that are taken up by the TonB/ExbB/ExbD-dependent transporter SusC. In the periplasm, oligosaccharides are further degraded by the neopullulanase SusA and the α-glucosidase SusB. The resulting glucose and maltose molecules are transported into the cytoplasm where they are further metabolized. IM, inner membrane. Created with BioRender.com.

Figure 3:. Fermentation is the primary means of generating cellular energy for commensal gut bacteria.

Diagram of representative fermentation pathways and products (blue) found in gut bacteria. Monosaccharides, derived from the degradation of complex polysaccharides for example, are converted to pyruvate via the Embden-Meyerhof-Parnas pathway, the Entner-Doudoroff pathway (mostly Gram-negative bacteria), or to a lesser extent the pentose phosphate pathway, or other, dedicated pathways. These reactions generally produce reduction equivalents, e.g. NADH, which is recycled in subsequent steps such as conversion of pyruvate to lactate, reduction of acetyl-CoA to ethanol. Alternatively, pyruvate can be converted in multiple steps to oxaloacetate and fumarate, which supports fumarate respiration (reductive branch of the TCA cycle). These reactions not only regenerate NAD⁺ but also allow for simple respiratory chains to function. Substrate level phosphorylation is the primary means of generating ATP, for example through the two-step conversion of acetyl-CoA to acetate (AckA-Pta pathway) or the conversion of butyryl-CoA to butyrate. F-Asn, Fructose-Asparagine, F-Asp, Fructose-Aspartate, Neu5Ac, N-acetylneuraminic acid (Sialic acid), ManNAc, N-acetylmannosamine, G6P, Glucose 6-phosphate, F6P, Fructose 6-phosphate, GADP, Glyceraldehyde 3-phosphate, DHAP, Dihydroxyacetone phosphate. Created with BioRender.com.

Figure 4:. Stickland fermentation and sulfur metabolism in gut bacteria.

(A) Examples of an oxidative (Ala, alanine) and two reductive (Gly, glycine; Pro, proline) Stickland fermentation reactions found in Clostridia are outlined. Oxidative deamination, for example deamination of alanine to pyruvate, is coupled with reductive deamination of another amino acid, for example glycine to acetyl-phosphate or proline to 5-aminovalerate. ATP is generated through the AckA-Pta pathway. Ac-CoA, Acetyl-CoA, Ac-P, Acetyl-phosphate. (B) Plant polysaccharide-derived sulfate is converted to sulfite via adenosine-5′-phosphosulfate. Bile salt hydrolase activity generates taurine was well as chenodeoxycholic or cholic acid. In the cytoplasm, taurine is converted to isethionate, which is cleaved into sulfite and acetaldehyde in a microcompartment. Alternatively, sulfoacetaldehyde can be converted directly to sulfite. Acetaldehyde can enter the AckA-Pta pathway. Reduction of adenosine-5′-phosphosulfate and sulfite (dissimilatory sulfite reduction) is coupled to an electron transport chain with lactate and formate as electron donors (not shown). Created with BioRender.com.

Figure 5:. Gut inflammation changes the availability of terminal electron acceptors.

(A) Hydrogen sulfide (H₂S) is detoxified to thiosulfate in the host mitochondria. During infection with enteric pathogens such as Salmonella, the local inflammatory response leads to the release of reactive oxygen (ROS) and nitrogen species (RNS) into the gut lumen. ROS oxidize thiosulfate to tetrathionate, which supports tetrathionate respiration in Salmonella. ROS and RNS form peroxynitrite, which decays to nitrate; nitrate in turn allows for nitrate respiration. Reduced production of butyrate due to gut microbiota dysbiosis causes a metabolic shift in epithelial cells, and oxygen enters the gut lumen. The emergence of electron acceptors enables Salmonella to utilize fermentation products. (B) During non-infectious colitis, such as in inflammatory bowel disease, the electron acceptors nitrate and oxygen become available. Utilization of L-lactate and formate as electron donors allow for respiration by facultative anaerobic bacteria (Proteobacteria). Respiring gut microbes outcompete fermenting bacteria, resulting in phylum-level changes in the microbiota composition (dysbiosis). Created with BioRender.com.