The role of the host gut microbiome in the pathophysiology of schistosomiasis.

The pathophysiology of schistosomiasis is linked to the formation of fibrous granulomas around eggs that become trapped in host tissues, particularly the intestines and liver, during their migration to reach the lumen of the vertebrate gut. While the development of Schistosoma egg-induced granulomas is the result of finely regulated crosstalk between egg-secreted antigens and host immunity, evidence has started to emerge of the likely contribution of an additional player-the host gut microbiota-to pathological processes that culminate with the formation of these tissue lesions. Uncovering the role(s) of schistosome-mediated changes in gut microbiome composition and function in granuloma formation and, more broadly, in the pathophysiology of schistosomiasis, will shed light on the mechanisms underlying this three-way parasite-host-microbiome interplay. Such knowledge may, in turn, pave the way towards the discovery of novel therapeutic targets and control strategies.

Gastrointestinal worms and bacteria: From association to intervention.

A plethora of studies, both experimental and epidemiological, have indicated the occurrence of associations between infections by gastrointestinal (GI) helminths and the composition and function of the host gut microbiota. Given the worldwide risk and spread of anthelmintic resistance, particularly for GI parasites of livestock, a better understanding of the mechanisms underpinning the relationships between GI helminths and the gut microbiome, and between the latter and host health, may assist the development of novel microbiome-targeting and other bacteria-based strategies for parasite control. In this article, we review current and prospective methods to manipulate the host gut microbiome, and/or to exploit the immune stimulatory and modulatory properties of gut bacteria (and their products) to counteract the negative impact of GI worm infections; we also discuss the potential applications of these intervention strategies in programmes aimed to aid the fight against helminth diseases of humans and livestock.

Baseline Gut Microbiota Composition Is Associated With Schistosoma mansoni Infection Burden in Rodent Models.

In spite of growing evidence supporting the occurrence of complex interactions between Schistosoma and gut bacteria in mice and humans, no data is yet available on whether worm-mediated changes in microbiota composition are dependent on the baseline gut microbial profile of the vertebrate host. In addition, the impact of such changes on the susceptibility to, and pathophysiology of, schistosomiasis remains largely unexplored. In this study, mice colonized with gut microbial populations from a human donor (HMA mice), as well as microbiota-wild type (WT) animals, were infected with Schistosoma mansoni, and alterations of their gut microbial profiles at 50 days post-infection were compared to those occurring in uninfected HMA and WT rodents, respectively. Significantly higher worm and egg burdens, together with increased specific antibody responses to parasite antigens, were observed in HMA compared to WT mice. These differences were associated to extensive dissimilarities between the gut microbial profiles of each HMA and WT groups of mice at baseline; in particular, the gut microbiota of HMA animals was characterized by low microbial alpha diversity and expanded Proteobacteria, as well as by the absence of putative immunomodulatory bacteria (e.g. Lactobacillus). Furthermore, differences in infection-associated changes in gut microbiota composition were observed between HMA and WT mice. Altogether, our findings support the hypothesis that susceptibility to S.mansoni infection in mice is partially dependent on the composition of the host baseline microbiota. Moreover, this study highlights the applicability of HMA mouse models to address key biological questions on host-parasite-microbiota relationships in human helminthiases.