Competition for Hydrogen Prevents Coexistence of Human Gastrointestinal Hydrogenotrophs in Continuous Culture

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 10 6 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.

Systems biology illuminates alternative metabolic niches in the human gut microbiome

“…Regardless of whether the previous annotation of this pathway (which has not been biochemically validated) is correct, reductive acetogenesis may not be thermodynamically favorable during in vitro growth in our anaerobic chamber, where the H 2 concentration is ≤ 5% (Smith et al, 2020). Blocking model flux through the carbon monoxide dehydrogenase reaction of this pathway increased growth dependency on uptake of both arginine and acetate, reflecting our experimental observations (Figure 3C).…”

A functional Wood–Ljungdahl pathway devoid of a formate dehydrogenase in the gut acetogens Blautia wexlerae, Blautia luti and beyond

“…Under standard conditions, reduction of sulfate to H 2 S is the energetically most favourable reaction (Thauer et al, 1977). Therefore, mathematical models suggested out-competition of acetogens in a homogenous culture with sulfate-reducing bacteria or methanogens when grown together on H 2 + CO 2 or H 2 + CO 2 + sulphate (Smith et al, 2020). Gut acetogens might play an important role in H 2 utilization in humans, which harbour only a small number of methanogens and sulfate-reducing bacteria (Hylemon et al, 2018).…”

“…Under standard conditions, reduction of sulfate to H 2 S is the energetically most favourable reaction with Δ G° ′= −152.2 kJ mol −1 (SO 4 2− + 4 H 2 + H + → HS − + 4 H 2 O), production of methane from CO 2 results in free energy of Δ G° ′= −131 kJ mol −1 (CO 2 + 4 H 2 → CH 4 + 2 H 2 O), the least energetic favourable reaction is acetogenesis from CO 2 (Δ G °′ = −95 kJ mol −1 ; 2 CO 2 + 4 H 2 → CH 3 COO − + H + + 2 H 2 O) (Thauer et al ., 1977). Therefore, mathematical models suggested out‐competition of acetogens in a homogenous culture with sulfate‐reducing bacteria or methanogens when grown together on H 2 + CO 2 or H 2 + CO 2 + sulphate (Smith et al ., 2020). Gut acetogens might play an important role in H 2 utilization in humans, which harbour only a small number of methanogens and sulfate‐reducing bacteria (Hylemon et al ., 2018).…”

Red seaweed supplementation suppresses methanogenesis in the rumen, revealing potentially advantageous traits among hydrogenotrophic bacteria

“…Addressing enteric methane emissions by diverting hydrogen from methanogenesis towards alternative pathways necessitates understanding the competitive interactions among hydrogenotrophic organisms 78 . MGYG000293775 has encoded functional capacity that may provide advantages over other hydrogenotrophs.…”