Biology subjects

Cantacessi, C.

Publications and source records attributed to Cantacessi, C..

4 recordsLinked to original sources

bioRxiv2026

Schistosoma mansoni infection enhances insertion sequence activity in the host gut microbiome

Schistosoma mansoni infection is associated with alterations of the host gut microbial community structure, yet its impact on microbial genome dynamics and horizontal gene transfer remains poorly understood. In this study, we investigated the activity of Mobile Genetic Elements (MGEs), and of Insertion Sequences (IS) in particular, in the gut microbiome of wild-type (WT) and human-microbiota-associated (HMA) mice. Taxonomic profiling revealed significant differences in bacterial diversity between WT and HMA mice, with reduced richness and alpha diversity observed in HMA gut microbiomes regardless of the infection status. Principal Coordinates Analysis demonstrated clear separation between microbial communities, reflecting differences in host background and bacterial composition. In contrast, differences were observed between plasmid and viral community profiles and between these and bacterial diversity, suggesting that different MGEs may follow distinct ecological dynamics within the gut microbiome. IS elements within bacterial genomes were widespread across all microbiome communities analysed in this study, with higher insertion counts observed not only in HMA compared to WT mice, but also in infected compared to uninfected mice. IS elements were predominantly associated with dominant gut bacterial taxa, particularly members of Bacteroidia and Clostridia. At the genomic level, insertion events occurred more frequently in intergenic regions than in coding sequences, suggesting a preferential selective pressure towards alteration of gene expression rather than gene disruption. Furthermore, IS activity was dominated by a subset of IS families, with consistent patterns observed across experimental groups. Notably, infection was associated with increased insertion frequencies across multiple taxa and IS families, suggesting enhanced mobilisation under conditions of host-associated stress (the physiological and molecular pressure experienced by microorganisms, pathogens, or the host itself during their interactions within a symbiotic or infected environment) and microbiome perturbation. Together, these findings demonstrate that S. mansoni infection may promote IS mobilisation in the mouse gut microbiome, potentially contributing to microbial genome plasticity and facilitating horizontal gene transfer within host-associated microbial communities.

bioinformatics↗

bioRxiv2025

Host microbiome determines host specificity of the human whipworm, Trichuris trichiura

Long-term whipworm-host co-evolution has resulted in tropism for the caecum of specific hosts, an organ with the densest microbial population in the body. Here, we demonstrate that the host specificity of human whipworms (Trichuris trichiura) is host microbiome-driven. We successfully establish a T. trichiura infection in a non-primate host using a humanised-microbiota mouse model. We further show, in vitro, that hatching of T. trichiura was triggered by mucosal scrapings of the caecum of human microbiota-associated mice, but not from wild-type mice, which only induced T. muris hatching. Comparative metagenomic analysis of the murine versus humanised microbiomes directly implicated specific bacterial species in T. trichiura egg hatching. Additionally, we demonstrate that host tissue does not directly determine host specificity, as T. trichiura readily infected mouse caecaloids. Our findings indicate that host-microbiome-whipworm co-evolution has resulted in exquisite bacterial-whipworm egg interactions critical for hatching and development of these parasites in their definitive hosts.

microbiology↗

bioRxiv2025

Enrichment of helminth mitochondrial genomes from faecal samples using hybridisation capture

New approaches are urgently needed to enrich rare or low-abundant DNA in complex samples. Soil-transmitted helminths (STHs) inhabit heterogeneous environments, including the gastrointestinal tract of their host as adults and are excreted as eggs and larvae in faeces, complicating our understanding of their biology and the use of genetic tools for species monitoring and population tracking. We have developed a hybridisation capture approach to enrich mitochondrial genome sequences of two STH species, the roundworm Ascaris lumbricoides and whipworm Trichuris trichiura, from extracted DNA from faecal material and worm specimens. Employing [~]1000 targeted probes, we achieved >6,000 and >12,000 fold enrichment for A. lumbricoides and T. trichiura, respectively, relative to direct whole genome shotgun (WGS) sequencing. Sequencing coverage was highly concordant with probe targets and correlated with the number of eggs per gram (EPG) of parasites present, from which DNA from as few as 336 EPG for Ascaris and 48 EPG for Trichuris were efficiently captured and sufficient to provide effective mitochondrial genome data. Finally, allele frequencies were highly concordant between WGS and hybridisation capture, suggesting little genetic information is lost with additional sample processing required for enrichment. Our hybridisation capture design and approach enables sensitive and scalable STH mitochondrial genome sampling from faecal DNA extracts and paves the way for broader hybridisation capture-based genome-wide applications and molecular epidemiology studies of STHs.

genomics↗

bioRxiv2018

Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection

The whipworm Trichuris trichiura is a soil-transmitted helminth that dwells in the epithelium of the caecum and proximal colon of their hosts causing the human disease, trichuriasis. Trichuriasis is characterized by colitis attributed to the inflammatory response elicited by the parasite while tunnelling through intestinal epithelial cells (IECs).\n\nThe IL-10 family of receptors, comprising combinations of subunits IL-10R, IL-10R{beta}, IL-22R and IL-28R, modulates intestinal inflammatory responses. Here we carefully dissected the role of these subunits in the resistance of mice to infection with T. muris, a mouse model of the human whipworm T. trichiura. Our findings demonstrate that whilst IL-22R and IL-28R are dispensable in the host response to whipworms, IL-10 signalling through IL-10R and IL-10R{beta} is essential to control caecal pathology, worm expulsion and survival during T. muris infections. We show that deficiency of IL-10, IL-10R and IL-10R{beta} results in dysbiosis of the caecal microbiota characterised by expanded populations of opportunistic bacteria of the families Enterococcaceae and Enterobacteriaceae. Moreover, breakdown of the epithelial barrier after whipworm infection in IL-10, IL-10R and IL-10R{beta}-deficient mice, allows the translocation of these opportunistic pathogens or their excretory products to the liver causing organ failure and lethal disease. Importantly, bone marrow chimera experiments indicate that signalling through IL-10R and IL-10R{beta} in haematopoietic cells, but not IECs, is crucial to control worm expulsion and immunopathology. These findings are supported by worm expulsion upon infection of conditional mutant mice for the IL-10R on IECs. Our findings emphasize the pivotal role of systemic IL-10R signalling on immune cells in promoting microbiota homeostasis and maintaining the intestinal epithelial barrier, thus preventing immunopathology during whipworms infections.\n\nAuthor summaryThe human gut is home to millions of bacteria, collectively called the microbiota, and also to parasites that include whipworms. The interactions between gut cells, the microbiota and whipworms define conditions for balanced parasitism. Cells lining the gut host whipworms but also interact with gut immune cells to deploy measures that control or expel whipworms whilst maintaining a barrier to prevent microbial translocation. Whipworms affect the composition of the microbiota, which in turn impacts the condition of the gut lining and the way in which immune cells are activated. In order to avoid tissue damage and disease, these interactions are tightly regulated. Here we show that signalling through a member of the IL-10 receptor family, IL-10R, in gut immune cells is critical for regulating of these interactions. Lack of this receptor on gut immune cells results in persistence of whipworms in the gut accompanied by an uncontrolled inflammation that destroys the gut lining. This tissue damage is accompanied by the overgrowth of members of the microbiota that act as opportunistic pathogens. Furthermore, the destruction of the gut barrier allows these bacteria to reach the liver where they cause organ failure and fatal disease.

immunology↗