Lactate can be produced by many gut bacteria, but in adults its accumulation in the colon is often an indicator of microbiota perturbation. Using continuous culture anaerobic fermentor systems, we found that lactate concentrations remained low in communities of human colonic bacteria maintained at pH 6.5, even when dl-lactate was infused at 10 or 20 mM. In contrast, lower pH (5.5) led to periodic lactate accumulation following lactate infusion in three fecal microbial communities examined. Lactate accumulation was concomitant with greatly reduced butyrate and propionate production and major shifts in microbiota composition, with Bacteroidetes and anaerobic Firmicutes being replaced by Actinobacteria, lactobacilli, and Proteobacteria. Pure-culture experiments confirmed that Bacteroides and Firmicutes isolates were susceptible to growth inhibition by relevant concentrations of lactate and acetate, whereas the lactate-producer Bifidobacterium adolescentis was resistant. To investigate system behavior further, we used a mathematical model (microPop) based on 10 microbial functional groups. By incorporating differential growth inhibition, our model reproduced the chaotic behavior of the system, including the potential for lactate infusion both to promote and to rescue the perturbed system. The modeling revealed that system behavior is critically dependent on the proportion of the community able to convert lactate into butyrate or propionate. Communities with low numbers of lactate-utilizing bacteria are inherently less stable and more prone to lactate-induced perturbations. These findings can help us to understand the consequences of interindividual microbiota variation for dietary responses and microbiota changes associated with disease states. IMPORTANCE Lactate is formed by many species of colonic bacteria, and can accumulate to high levels in the colons of inflammatory bowel disease subjects. Conversely, in healthy colons lactate is metabolized by lactate-utilizing species to the short-chain fatty acids butyrate and propionate, which are beneficial for the host. Here, we investigated the impact of continuous lactate infusions (up to 20 mM) at two pH values (6.5 and 5.5) on human colonic microbiota responsiveness and metabolic outputs. At pH 5.5 in particular, lactate tended to accumulate in tandem with decreases in butyrate and propionate and with corresponding changes in microbial composition. Moreover, microbial communities with low numbers of lactate-utilizing bacteria were inherently less stable and therefore more prone to lactate-induced perturbations. These investigations provide clear evidence of the important role these lactate utilizers may play in health maintenance. These should therefore be considered as potential new therapeutic probiotics to combat microbiota perturbations.
Commensal butyrate-producing bacteria belonging to the Firmicutes phylum are abundant in the human gut and are crucial for maintaining health. Currently, insight is lacking into how they target otherwise indigestible dietary fibers and into the trophic interactions they establish with other glycan degraders in the competitive gut environment.
ABSTRACTβ-Mannans are hemicelluloses that are abundant in modern diets as components in seed endosperms and common additives in processed food. Currently, the collective understanding of β-mannan saccharification in the human colon is limited to a few keystone species, which presumably liberate low-molecular-weight mannooligosaccharide fragments that become directly available to the surrounding microbial community. Here we show that a dominant butyrate-producer in the human gut, Faecalibacterium prausnitzii, is able to acquire and degrade various β-mannooligosaccharides (β-MOS), which are derived by the primary mannanolytic activity of neighboring gut microbiota. Detailed biochemical analyses of selected protein components from their two β-mannooligosaccharides (β-MOS) utilization loci (FpMULs) supported a concerted model whereby the imported β-MOS are stepwise disassembled intracellularly by highly adapted enzymes. Coculturing experiments of F. prausnitzii with the primary degrader Bacteroides ovatus on polymeric β-mannan resulted in syntrophic growth and production of butyrate, thus confirming the high efficiency of the FpMULs’ uptake system. Genomic comparison with human F. prausnitzii strains and analyses of 2441 public human metagenomes revealed that FpMULs are highly conserved and distributed worldwide. Together, our results provide a significant advance in the knowledge of β-mannans metabolism and the degree to which its degradation is mediated by cross-feeding interactions between prominent beneficial microbes in the human gut.ImportanceCommensal butyrate-producing bacteria belonging to the Firmicutes phylum are abundant in the human gut and are crucial for maintaining health. Currently, insight is lacking into how they target otherwise indigestible dietary fibers and into the trophic interactions they establish with other glycan degraders in the competitive gut environment. By combining cultivation, genomic and detailed biochemical analyses this work reveals the mechanism enabling F. prausnitzii, as a model clostridial cluster IV Firmicute, to cross-feed and access β-mannan-derived oligosaccharides released in the gut ecosystem by the action of primary degraders. A comprehensive survey of human gut metagenomes shows that FpMULs are ubiquitous in human populations globally, highlighting the importance of microbial metabolism of β-mannans/β-MOS as a common dietary component. Our findings provide a mechanistic understanding of the β-MOS utilization capability by F. prausnitzii that may be exploited to select dietary formulations specifically boosting this beneficial symbiont, thus butyrate production, in the gut.
Flin.ti.bac'ter. L. masc. n. bacter rod; N.L. masc. n. Flintibacter rod‐shaped bacterium named after Harry J. Flint, a microbiologist from Aberdeen, UK, who dedicated his career to the investigation of gut bacteria, especially butyrate producers and their role in health and disease. Firmicutes / Clostridia / Clostridiales / Ruminococcaceae / Flintibacter Cells are small irregular needle‐like rods that can form long filaments. Usually gives a Gram‐negative‐staining reaction. Endospores are not observed, and cells are nonmotile. Strictly anaerobic. Optimum growth between 30 and 40°C and in the presence of NaCl up to 1%. Oxidase‐ and catalase‐negative. Grows on Wilkins‐Chalgren medium and can utilize several carbon sources. Can metabolize the amino acids glutamine and glutamate, but fails to grow on leucine, asparagine, lysine, arginine, and aspartic acid. Grows in the presence of glucosamine and raffinose. The end products of fermentation are formate, acetate, and butyrate. The main cellular fatty acids are iso‐C 17:1 /anteiso‐C 17:1 (16.1%), iso‐C 19:1 (14.8%), C 18:1 ω9 c (13.5%), C 12:0 (12.2%), C 14:0 (11.4%), and C 16:0 (11.2%). The nearest phylogenetic neighbors are Intestinimonas butyriciproducens , Pseudoflavonifractor capillosus, Flavonifractor plautii, Lawsonibacter asaccharolyticus , and Clostridium viride . The genus accommodates the species Flintibacter butyricus . Isolated from the cecal contents of a wild‐type mouse. DNA G + C content (mol%) : 58 (draft genome). Type species : Flintibacter butyricus Lagkouvardos, Pukall, Abt, Foesel, Meier‐Kolthoff, Kumar, et al. 2016c, 4301 VP (Effective publication: Lagkouvardos, Pukall, Abt, Foesel, Meier‐Kolthoff, Kumar, et al., 2016b, 12).
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