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Is there a Correlation between Body Size and Gut Microbiome?

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You might be surprised to learn that vertebrate body size, which varies dramatically, is positively associated with gut microbiome alpha diversity, which refers to the measure of the variety and abundance of species within a specific ecosystem or community (like the gut microbiome of an individual organism). Larger animals, with larger guts, tend to harbour more microbes. Previous studies used an older method involving 16S rRNA gene amplicons and electrophoresis to quantify alpha diversity. This method allowed for the identification and quantification of different taxa. Recent research with a large human cohort has also shown that taller individuals have greater gut microbiome alpha diversity. This pattern is similar to the species-area relationships (SARs) observed in ecosystems where larger areas host more species. However, the mechanisms driving this SAR-like behaviour in the gut remain unexplored.

Some literature suggests that neutral processes, like those described by island biogeography theory (IBT), could explain these patterns. IBT posits that larger areas support more individuals, leading to a greater number of species. It was hypothesized that IBT might explain the size-diversity relationships in vertebrates and humans. To test this, Sarmiento et al. 2024 built an individual-based model simulating IBT in the gut, varying system length and incorporating immigration, emigration, and reproduction (Figure 1). The simulations, which accounted for vertebrate body sizes and human height variation, were then compared to empirical data, revealing intriguing insights into gut microbiome diversity. This individual-based model showed that gut length positively correlates with species diversity, mirroring patterns seen in vertebrates and humans. This suggests that even basic models, which assume that all species have an equal chance of surviving and reproducing, can help explain the big-picture patterns we see in the variety of microbes living in the guts of different animals and humans. The way body size and gut bacteria diversity work together might influence the risk of getting gut infections.

Lower gut microbiome alpha diversity is associated with higher risk of infections, likely due to the niche saturation hypothesis. This hypothesis suggests that a diverse community of microbes occupies all available ecological niches, leaving little room for harmful pathogens to take hold and cause infections.

A simulation model of gut microbiome diversity over time using an individual-based approach. At the initial time point (T0), individuals are generated from a lognormal population and enter the system at a fixed immigration rate, while individuals reproduce randomly and exit the system through the outlet. If the system has not reached stationarity, the simulation proceeds to the next time step (T1001 the 1001th time step), repeating the process until stationarity is achieved. The graph at the bottom of the image shows the diversity increasing over time, eventually reaching a stable level, indicating the point of stationarity in the simulation. Image credited to Sarmiento et al. (2024).

Clostridioides difficile, a common hospital-acquired enteric pathogen, is often linked to disruptions in gut microbiota diversity, such as those caused by antibiotics or diarrhea. Infections are usually treated with oral antibiotics, but recurrence is common, especially in individuals with initially low microbiome diversity. Clinically, lower gut microbiome alpha diversity increases susceptibility to pathogens like Clostridioides difficile. The results highlighted in this paper indicated that shorter individuals might be more prone to enteric infections due to lower diversity. Based on this they proposed an mechanistic explanation based on the island biogeography theory adapted to the gut environment. Dietary factors, particularly vegetable intake, significantly influence gut diversity and infection risk. A higher intake of vegetables was strongly associated with greater gut diversity and lower infection risk, emphasizing the importance of diet in managing gut health.

Previous studies have identified various factors influencing gut microbiome alpha diversity in vertebrates, including gut morphology, evolutionary history, and diet. For instance, animals with more complex gut anatomies, like foregut and hindgut fermenters, exhibit higher microbial richness than carnivores. This research found a strong correlation between host body size and gut alpha diversity, independent of diet, suggesting additional mechanisms at work.

In humans, height is positively associated with gut microbiome alpha diversity, irrespective of age, sex, BMI, bowel movement frequency, and diet. Studies show that factors such as age, with varying impacts on diversity, and sex, where females often have higher diversity, affect gut microbiome diversity. Obesity and BMI negatively correlate with diversity due to lower fibre intake and increased inflammation. Constipation correlates with higher diversity, while diarrhoea correlates with lower diversity. Plant-based diets also promote higher alpha diversity.

This study showed that gut alpha diversity mediated the effects of both height and vegetable consumption in humans with Clostridioides difficile infection history. Height’s effects were completely mediated by diversity, while vegetable consumption had a partial mediation effect, meaning it influenced gut microbiome health both directly and indirectly through diversity. This indicates that while body size plays a role, dietary habits have a more substantial impact on gut microbiome health. Statistical analysis confirmed the mediation effects, highlighting the relationship between these factors.

In this study, the researchers considered several factors to explain the link between body size and gut microbiome diversity, but none fully accounted for the observed patterns. While their gut model offers a possible explanation, other factors, like the diversity of gut microbes in early life, might also affect adult height. The model was simplified but still captured important aspects like new microbes entering the gut (immigration), how they grow, and how they move in one direction through the digestive system, all of which influence the variety of microbes in the gut. However, this study may have been underpowered because the sample size or diversity of participants might not have been large enough to detect a strong link between height and the history of microbial infections. This suggests that more research is needed with larger and more varied groups of people to better understand how height might influence the risk of these infections. As the science in this area is still developing, these findings highlight the importance of continued investigation to uncover more definitive answers.

Link to the original post: Katherine Ramos Sarmiento, Alex Carr, Christian Diener, Kenneth J Locey, Sean M Gibbons, Island biogeography theory provides a plausible explanation for why larger vertebrates and taller humans have more diverse gut microbiomes, The ISME Journal, Volume 18, Issue 1, January 2024, wrae114, https://doi.org/10.1093/ismejo/wrae114

Featured image: created by by author in DALL-E3