Impacts of plant-based foods in ancestral hominin diets on the metabolism and function of gut microbiota in vitro

Abstract

Ancestral human populations had diets containing more indigestible plant material than present-day diets in industrialized countries. One hypothesis for the rise in prevalence of obesity is that physiological mechanisms for controlling appetite evolved to match a diet with plant fiber content higher than that of present-day diets. We investigated how diet affects gut microbiota and colon cells by comparing human microbial communities with those from a primate that has an extreme plant-based diet, namely, the gelada baboon, which is a grazer. The effects of potato (high starch) versus grass (high lignin and cellulose) diets on human-derived versus gelada-derived fecal communities were compared in vitro. We especially focused on the production of short-chain fatty acids, which are hypothesized to be key metabolites influencing appetite regulation pathways. The results confirmed that diet has a major effect on bacterial numbers, short-chain fatty acid production, and the release of hormones involved in appetite suppression. The potato diet yielded greater production of short-chain fatty acids and hormone release than the grass diet, even in the gelada cultures, which we had expected should be better adapted to the grass diet. The strong effects of diet on hormone release could not be explained, however, solely by short-chain fatty acid concentrations. Nuclear magnetic resonance spectroscopy found changes in additional metabolites, including betaine and isoleucine, that might play key roles in inhibiting and stimulating appetite suppression pathways. Our study results indicate that a broader array of metabolites might be involved in triggering gut hormone release in humans than previously thought.

Importance: One theory for rising levels of obesity in western populations is that the body's mechanisms for controlling appetite evolved to match ancestral diets with more low-energy plant foods. We investigated this idea by comparing the effects of diet on appetite suppression pathways via the use of gut bacterial communities from humans and gelada baboons, which are modern-day primates with an extreme diet of low-energy plant food, namely, grass. We found that diet does play a major role in affecting gut bacteria and the production of a hormone that suppresses appetite but not in the direction predicted by the ancestral diet hypothesis. Also, bacterial products were correlated with hormone release that were different from those normally thought to play this role. By comparing microbiota and diets outside the natural range for modern humans, we found a relationship between diet and appetite pathways that was more complex than previously hypothesized on the basis of more-controlled studies of the effects of single compounds.

FIG 1

The mean densities of total bacteria and each of the five focal taxa during the experiment. Colors indicate diet: black = control; green = grass; brown = potato. Solid lines = gelada cultures. Dashed lines = human cultures. Standard errors are shown. All taxa were significantly more abundant in human cultures (all t > 3, all P < 0.005) except lactobacilli (t = 1.0, P = 0.32).

FIG 2

Bacterial density (cells/ml) of five focal taxa enumerated using FISH. Compositions are shown for the initial community and for each dietary control at the end of the experiment (72 h) for human-derived cultures (A) and gelada-derived cultures (B) in turn.

FIG 3

Total short-chain fatty acid production over time in human (A) and gelada (B) cultures. Black = control diet; brown = potato-supplemented diet; green = grass-supplemented diet.

FIG 4

Summary of the results of linear models of production rates of SCFA depending on diet and community treatment (shaded boxes), SCFA concentration, and taxon counts (white boxes). Production rates were calculated as the changes in the concentration of each SCFA and lactate between time steps, and arrows show which variables at the initial time step correlate with those. Only terms retained as significant following simplification of linear models are shown, and numbers indicate the t value from linear models. Both acetate and propionate production rates were highest in human-derived cultures with the potato diet: the t value is for the interaction term between human and potato.

FIG 5

PYY release from colon cells exposed to effluent from in vitro microbial cultures with respect to the source community (gelada versus human) and the diet (control versus grass versus potato). To control for variation in the number of L cells per well, PYY release is expressed as follows: [(the amount of PYY measured in the supernatant)/(the amount of PYY measured in the supernatant plus lysed cells)] × 100. Results for samples from 0 and 10 h were pooled for each treatment, as time had no significant effect.

FIG 6

Plot of LS-DA coefficients comparing the metabolic profiles of human and gelada batch cultures at 0 h (P = 4.03 × 10⁻⁴) (A), 8 to 24 h following potato supplementation (B), and 8 to 24 h following grass supplementation (C).

FIG 7

PLS model identifying metabolic correlates of PYY release in effluent from each culture. Communities, diets, and times were pooled for the analysis.