A framework for testing the impact of co-infections on host gut microbiomes

Abstract

Parasitic infections disturb gut microbial communities beyond their natural range of variation, possibly leading to dysbiosis. Yet it remains underappreciated that most infections are accompanied by one or more co-infections and their collective impact is largely unexplored. Here we developed a framework illustrating changes to the host gut microbiome following single infections, and build on it by describing the neutral, synergistic or antagonistic impacts on microbial α- and ß-diversity expected from co-infections. We tested the framework on microbiome data from a non-human primate population co-infected with helminths and Adenovirus, and matched patterns reported in published studies to the introduced framework. In this case study, α-diversity of co-infected Malagasy mouse lemurs (Microcebus griseorufus) did not differ in comparison with that of singly infected or uninfected individuals, even though community composition captured with ß-diversity metrices changed significantly. Explicitly, we record stochastic changes in dispersion, a sign of dysbiosis, following the Anna-Karenina principle rather than deterministic shifts in the microbial gut community. From the literature review and our case study, neutral and synergistic impacts emerged as common outcomes from co-infections, wherein both shifts and dispersion of microbial communities following co-infections were often more severe than after a single infection alone, but microbial α-diversity was not universally altered. Important functions of the microbiome may also suffer from such heavily altered, though no less species-rich microbial community. Lastly, we pose the hypothesis that the reshuffling of host-associated microbial communities due to the impact of various, often coinciding parasitic infections may become a source of novel or zoonotic diseases.

Two decades of tuberculosis surveillance reveal disease spread, high levels of exposure and mortality and marked variation in disease progression in wild meerkats

“…While we lack detailed information on pathogen communities in wild meerkats, nematode infections are present in our study population (Smyth & Drea, 2016) and thus might contribute to variation in TB progression in this species. Moreover, climate change and environmental or social disturbances can drive co‐infections and might even facilitate the emergence of novel pathogens or the re‐emergence of endemic, but historically unproblematic pathogens via shifts in host‐associated gut microbiota (Risely et al., 2022; Schmid et al., 2022).…”

Idiosyncratic effects of coinfection on the association between systemic pathogens and the gut microbiota of a wild rodent, the bank vole Myodes glareolus

“…While multiple studies have indicated that pathogens can affect the gut microbiota of their wildlife host (Aivelo & Norberg, 2018; Wasimuddin et al, 2019), very few of these have considered possible effects of coinfection (Sabey et al, 2021; Schmid et al, 2022). Yet, coinfections are ubiquitous in wildlife (Hoarau et al, 2020), and indeed nearly 19% of voles in our study were coinfected (Figure 1).…”

“…Ap‐N, Ap‐S and Ap‐C), irrespective of the specific coinfections (Table S1). Furthermore, we used a framework proposed by Schmid et al (2022) to compare the effects of coinfections on gut microbiota with those of a single infection. The framework defines ‘synergistic’ effects of coinfection as those that exacerbate changes in the gut microbiota.…”

“…so that the microbiota becomes more like that of uninfected animals) the effects of coinfection are described as antagonistic. Effects of coinfection are neutral if they do not differ from those of a single‐pathogen infection (Schmid et al, 2022).…”

“…While multiple studies have indicated that pathogens can affect the gut microbiota of their wildlife host (Aivelo & Norberg, 2018;Wasimuddin et al, 2019), very few of these have considered possible effects of coinfection (Sabey et al, 2021;Schmid et al, 2022).…”