Prebiotics and Community Composition Influence Gas Production of the Human Gut Microbiota

Abstract

Prebiotics confer benefits to human health, often by promoting the growth of gut bacteria that produce metabolites valuable to the human body, such as short-chain fatty acids (SCFAs). While prebiotic selection has strongly focused on maximizing the production of SCFAs, less attention has been paid to gases, a by-product of SCFA production that also has physiological effects on the human body. Here, we investigate how the content and volume of gas production by human gut microbiota are affected by the chemical composition of the prebiotic and the community composition of the microbiota. We first constructed a linear system model based on mass and electron balance and compared the theoretical product ranges of two prebiotics, inulin and pectin. Modeling shows that pectin is more restricted in product space, with less potential for H2 but more potential for CO2 production. An ex vivo experimental system showed pectin degradation produced significantly less H2 than inulin, but CO2 production fell outside the theoretical product range, suggesting fermentation of fecal debris. Microbial community composition also impacted results: methane production was dependent on the presence of Methanobacteria, while interindividual differences in H2 production during inulin degradation were driven by a Lachnospiraceae taxon. Overall, these results suggest that both the chemistry of the prebiotic and the composition of the microbiota are relevant to gas production. Metabolic processes that are relatively prevalent in the microbiome, such as H2 production, will depend more on substrate, while rare metabolisms such as methanogenesis depend more strongly on microbiome composition. IMPORTANCE Prebiotic fermentation in the gut often leads to the coproduction of short-chain fatty acids (SCFAs) and gases. While excess gas production can be a potential problem for those with functional gut disorders, gas production is rarely considered during prebiotic design. In this study, we combined the use of theoretical models and an ex vivo experimental platform to illustrate that both the chemical composition of the prebiotic and the community composition of the human gut microbiota can affect the volume and content of gas production during prebiotic fermentation. Specifically, more prevalent metabolic processes such as hydrogen production were strongly affected by the oxidation state of the probiotic, while rare metabolisms such as methane production were less affected by the chemical nature of the substrate and entirely dependent on the presence of Methanobacteria in the microbiota.

Reshaping of bacterial molecular hydrogen metabolism contributes to the outgrowth of commensal E. coli during gut inflammation

“…Hydrogenase activity can be predicted based on primary sequence ( Søndergaard et al, 2016 ). The HydDB database has been widely utilized to classify hydrogenases ( Dong, 2020 ; Mei, 2020 ; Panwar, 2020 ; Park et al, 2020 ; Picone et al, 2020 ; Stairs et al, 2020 ; Wong, 2020 ; Yu et al, 2020 ). We confirmed the reliability of gene annotations in the HydDB database using a simulated metagenomic dataset of hydrogenase-containing and hydrogenase-free genomes (see Materials and methods for details).…”

Dietary Fiber Modulates the Fermentation Patterns of Cyanidin-3-O-Glucoside in a Fiber-Type Dependent Manner

“…The fermentation of carbohydrates by human gut microbiota usually produces gases. Production of H 2 is often necessary for the cycling of NAD + /NADH during fermentation, and CO 2 is released whenever decarboxylation occurs [ 31 ]. C3G did not have sufficient carbohydrates for the fermentation by gut microbiota; therefore, the gas volume of C group was very low ( Figure 2 A).…”

“…C3G did not have sufficient carbohydrates for the fermentation by gut microbiota; therefore, the gas volume of C group was very low ( Figure 2 A). The chemical composition of the prebiotics and the composition of the microbiota are related to the amount of produced gas during fermentation [ 31 ]. A previous study showed that inulin has a higher potential to produce H 2 than pectin during in vitro fermentation, due to its composition, and its total gas production was significantly higher than pectin [ 31 ].…”

“…The chemical composition of the prebiotics and the composition of the microbiota are related to the amount of produced gas during fermentation [ 31 ]. A previous study showed that inulin has a higher potential to produce H 2 than pectin during in vitro fermentation, due to its composition, and its total gas production was significantly higher than pectin [ 31 ]. This result is similar to that in this study; the gas production of FOS is significantly higher than that of PEC.…”

From taxonomy to metabolic output: what factors define gut microbiome health?

“…Thus, large-scale quantitative validation experiments are necessary for testing these models, where in vivo microbial growth rates and metabolite fluxes are measured to identify which metabolic processes are captured well by the model and which ones are not. Ex vivo growth experiments, where fecal samples are incubated under anaerobic conditions with a wide array of dietary metabolites, represent a promising high-throughput approach to observing gut microbial community metabolic output in the absence of the host 161 , 162 . Similarly, humanized gnotobiotic mice may prove to be a key tool in improving metagenome-scale metabolic models, by providing a well-controlled in vivo experimental model to optimize metabolic predictions.…”