Microbial lactate utilisation and the stability of the gut microbiome

Abstract

The human large intestinal microbiota thrives on dietary carbohydrates that are converted to a range of fermentation products. Short-chain fatty acids (acetate, propionate and butyrate) are the dominant fermentation acids that accumulate to high concentrations in the colon and they have health-promoting effects on the host. Although many gut microbes can also produce lactate, it usually does not accumulate in the healthy gut lumen. This appears largely to be due to the presence of a relatively small number of gut microbes that can utilise lactate and convert it to propionate, butyrate or acetate. There is increasing evidence that these microbes play important roles in maintaining a healthy gut environment. In this review, we will provide an overview of the different microbes involved in lactate metabolism within the gut microbiota, including biochemical pathways utilised and their underlying energetics, as well as regulation of the corresponding genes. We will further discuss the potential consequences of perturbation of the microbiota leading to lactate accumulation in the gut and associated disease states and how lactate-utilising bacteria may be employed to treat such diseases.

Postbiotics and Their Health Modulatory Biomolecules

“…As illustrated in Figure 1 , butyrate is produced by a distinct group of gut bacteria via either the CoA-transferase or butyrate kinase pathways [ 23 , 24 , 25 ]. Butyrate can only be produced by a distinct group of gut microbes, including Faecalibacterium prausnitzii and Eubacterium rectale [ 26 ]. A number of studies have identified that butyrate-producing bacteria are depleted in the gut microbiota of patients with inflammatory bowel diseases (including Crohn’s disease and ulcerative colitis) and colorectal cancer compared to healthy people [ 21 , 27 ].…”

“…Acetate is the most abundant SCFA in the gut reaching a molar ratio three times larger than butyrate and propionate [ 16 , 26 , 33 ]. Acetate is produced through the fermentation of dietary fibres by gut bacteria, including Ruminococcus spp., Prevotella spp., Bifidobacterium spp.…”

“…The postbiotic preparations of lactic acid bacteria are rich in lactate and acetate that can have a positive down-stream effect on butyrate and propionate concentrations in the gut when converted through cross-feeding by endogenous butyrate and propionate-producers. As illustrated in Figure 1 , lactate can be converted to butyrate via the CoA-transferase pathway by microbes, such as Anaerobutyricum and Anaerostipes species [ 23 , 24 , 26 ]. Lactate can also be converted to propionate via two pathways, namely the acrylate pathway by microbes, including Coprococcus catus and Megasphaera elsdenii , or the succinate pathway by microbes, including the Veillonella species [ 23 , 24 , 26 ].…”

“…As illustrated in Figure 1 , lactate can be converted to butyrate via the CoA-transferase pathway by microbes, such as Anaerobutyricum and Anaerostipes species [ 23 , 24 , 26 ]. Lactate can also be converted to propionate via two pathways, namely the acrylate pathway by microbes, including Coprococcus catus and Megasphaera elsdenii , or the succinate pathway by microbes, including the Veillonella species [ 23 , 24 , 26 ]. However, where butyrate and propionate producers are not present in the gut, as is the case in some disease states, the increasing concentrations of lactate and acetate will not result in an increase in butyrate or propionate [ 21 , 27 ].…”

Biological Relevance of Intestinal Gases in Healthy Humans

“…Colonic CO2 is a fermentative subproduct of the bicarbonate/acid reaction performed by commensals such as Bifidobacteria and butyrate-producing Clostridial clusters(Heresbach et al, 1995;Rivière et al, 2016). Short-chain fatty acids (acetate, propionate and butyrate) are the dominant fermentation acids that accumulate to high concentrations in the colon(Louis et al, 2022). The extreme acid load associated with high colonic p CO2 is partially counteracted by the proximal colon epithelium's apical membrane, that provides a significant resistance towards CO2 diffusion and confers cellular protection(Endeward and Gros, 2005).The intestinal CO2 enters red blood cells and is converted to carbonic acid, which dissociates to hydrogen ion and bicarbonate.…”