Abstract
Understanding the metabolic dynamics of the human gastrointestinal tract (GIT) microbiota is of growing importance as research continues to link the microbiome to host health status. Microbial strains that metabolize hydrogen have been associated with a variety of both positive and negative host nutritional and health outcomes, but limited data exists for their competition in the GIT. To enable greater insight into the behaviour of these microbes, a mathematical model was developed for the metabolism and growth of the three major hydrogenotrophic groups: sulphate-reducing bacteria (SRB), methanogens and reductive acetogens. In batch culture simulations with abundant sulphate and hydrogen, the SRB outcompeted the methanogen for hydrogen due to having a half-saturation constant 106 times lower than that of the methanogen. The acetogen, with a high model threshold for hydrogen uptake of around 70 mM, was the least competitive. Under high lactate and zero sulphate conditions, hydrogen exchange between the SRB and the methanogen was the dominant interaction. The methanogen grew at 70% the rate of the SRB, with negligible acetogen growth. In continuous culture simulations, both the SRB and the methanogen were washed out at dilution rates above 0.15 h−1 regardless of substrate availability, whereas the acetogen could survive under abundant hydrogen conditions. Specific combinations of conditions were required for survival of more than one hydrogenotroph in continuous culture, and survival of all three was not possible. The stringency of these requirements and the inability of the model to simulate survival of all three hydrogenotrophs in continuous culture demonstrates that factors outside of those modelled are vital to allow hydrogenotroph coexistence in the GIT.
Highlights
The human gastrointestinal tract (GIT) is home to a vast number of microbes that survive via metabolism of dietary and endogenous substrates, or via cross-feeding on molecules released by other members of the microbiota
Both the sulphate-reducing bacteria (SRB) and acetogen components of the model are based on previously published model structures for Desulfovibrio vulgaris and Blautia hydrogenotrophica, respectively (Smith et al, 2019a, 2020), with minor notation alterations and the removal of mass transfer from the SRB model
A comparison of the half-saturation and threshold parameter values for the three hydrogenotrophs shows the hierarchy in affinities for this substrate: the model estimates for the hydrogen half-saturation constants of the SRB and the methanogen are 1.69 × 10−5 mM and 10.63 mM, respectively (Table 1), while the threshold for hydrogen uptake for the acetogen is estimated at around 70 mM (Leclerc et al, 1997; Smith et al, 2020)
Summary
The human gastrointestinal tract (GIT) is home to a vast number of microbes that survive via metabolism of dietary and endogenous substrates, or via cross-feeding on molecules released by other members of the microbiota. There are three major functional groups that metabolize hydrogen: the sulphate-reducing bacteria (SRB), the methanogens and the reductive acetogens Each of these hydrogenotrophic functional groups or their metabolic products have been linked to nutritional and health impacts upon the host: hydrogen sulphide, produced by the SRB, has been investigated for its genotoxic effect on the GIT epithelium (Attene-Ramos et al, 2010); methane, produced by the methanogens, has been associated with constipation (Ghoshal et al, 2016); and acetate, produced by the acetogens, is readily absorbed by the host for use as an energy source (Morrison and Preston, 2016), but can be cross-fed upon by other members of the microbiota (Falony et al, 2006). The modelling presented here provides an unprecedented theoretical insight into the dynamics of these interactions This model includes the hydrogenotrophic metabolic pathways of each group, as well as lactate oxidation by the SRB, which can be a source of hydrogen. The hypothesis here was that the model would reveal what conditions were necessary for hydrogenotroph coexistence, as well as the conditions that would favour one group over the others
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