Anne Majgaard Jensen: Diet-Induced Changes in Gut Microbiomes of Parasites and Hosts

BACKGROUND
Parasitic infections are a major challenge for both human and animal health worldwide, with intestinal helminths infecting over a billion people and causing significant disease and economic losses. These parasites live in close association with the host gut environment, where they interact with both the host immune system and complex microbial communities, known as the gut microbiota. Diet is one of the main factors shaping this microbiota and can rapidly alter its composition and function. Emerging evidence shows that such diet-induced changes influence host susceptibility to parasitic infections.

Interestingly, many parasites themselves harbour distinct microbial communities. These microbiomes may play roles in parasite physiology, survival, and interaction with the host. However, it remains unclear whether parasite-associated microbiomes are shaped by the host environment or actively maintained by the parasite, and how diet-induced microbial changes influence these interactions.

This PhD project investigated how dietary modulation of the host gut microbiota affects the host’s susceptibility to parasite infections, host responses, and parasite-associated microbiomes. Using experimental models in zebrafish and mice infected with intestinal helminths and a protozoan parasite, the project combined microbiome analysis, metagenomics, and transcriptomics to explore host–microbiota–parasite interactions.

Overall, the project aimed to improve understanding of how diet influences parasitic infections and to identify mechanisms that could support new strategies for parasite control.

PURPOSE
The purpose of this PhD project was to investigate how diet-induced changes in the host gut microbiota influence the host’s susceptibility to parasite infections, host immune responses, and parasite-associated microbiomes.

The project specifically aimed to determine whether parasite-associated microbiomes reflect changes in the host microbiome or remain stable, and whether such microbial interactions contribute to parasite survival or expulsion.

Using zebrafish and mouse infection models, the thesis examined intestinal helminths (Trichuris muris and Pseudocapillaria tomentosa) and a protozoan parasite (Ichthyophthirius multifiliis) across different dietary interventions, including fibres and milk-derived glycans.

The project further aimed to characterise both taxonomic and functional changes in host and parasite microbiomes using metagenomics, and to assess host and parasite transcriptional responses to infection.

Overall, the goal was to understand the role of diet and microbiomes in host–parasite interactions and identify mechanisms underlying diet-driven differences in infection outcomes.

RESULTS
This PhD project demonstrated that diet is a key driver of host gut microbiota composition and strongly influences susceptibility to intestinal helminth infections. Diets such as high-fat feed and specific glycans increased parasite burdens, while non-fermentable fibres promoted parasite expulsion. In contrast, diet did not affect infection levels of the extraintestinal parasite Ichthyophthirius multifiliis, indicating that diet effects depend on direct interaction with the gut environment.

Across all models, parasite-associated microbiomes were highly stable and remained compositionally distinct from those of their hosts, despite major diet-induced changes in host gut microbiota. This indicates strong compartmentalisation and suggests that parasite microbiomes are selectively maintained rather than passively acquired.

Metagenomic analyses further showed that parasite microbiomes differ functionally from host microbiomes, with enrichment of pathways related to stress responses and structural glycan degradation, whereas host microbiomes were enriched for pathways associated with dietary substrates. Importantly, parasite microbiome composition did not differ between worms that persisted and those that were expelled.

Host transcriptional responses varied depending on model and diet, but in some cases, increased parasite burdens occurred without major changes in classical anti-parasitic immune pathways. Instead, parasite expulsion was associated with transcriptional stress responses within the parasite itself, likely driven by host-mediated pressures.

Overall, the findings show that diet shapes infection outcomes primarily through changes in the host environment rather than through alterations in parasite-associated microbiomes.

THE FUTURE
This thesis highlights the importance of diet in shaping host susceptibility to parasitic infections and opens new avenues for research into microbiome-based interventions. Future studies should focus on identifying the specific dietary components and microbial metabolites responsible for altered infection outcomes. In particular, short-chain fatty acids, mucin-derived sugars, and other metabolites represent promising candidates for mechanistic studies.

Further work is needed to understand how parasite-associated microbiomes are established and maintained. Experimental approaches using controlled microbial communities, antibiotics, or defined bacterial consortia could clarify whether specific microbes contribute to parasite fitness. Sampling parasites across life stages may also reveal whether their microbiomes change during development.

Another key direction is to investigate how host factors, including immune responses and epithelial dynamics, interact with diet and microbiota to influence parasite survival. Integrating time-resolved transcriptomics and controlled immune manipulations could help identify the signals driving parasite expulsion.

Ultimately, this research supports the potential for developing dietary or microbiome-based strategies to control parasitic infections. Such approaches may reduce reliance on antiparasitic drugs and contribute to more sustainable parasite management in both human and animal health systems.

For more information: anne.majgaard@sund.ku.dk