With an estimated 1031 particles on earth, bacteriophages are the most abundant genomic entities across all habitats and important drivers of microbial communities. Growing evidence suggest that they play roles in intestinal human microbiota homeostasis, and recent metagenomics studies on the viral fraction of this ecosystem have provided crucial information about their diversity and specificity. However, the bacterial hosts of this viral fraction, a necessary information to characterize further the balance of these ecosystems, remain poorly characterized. Here we unveil, using an enhanced metagenomic Hi-C approach, a large network of 6,651 host-phage relationships in the healthy human gut allowing to study in situ phage-host ratio. We notably found that half of these contigs appear to be sleeping prophages whereas ¼ exhibit a higher coverage than their associated MAG representing potentially active phages impacting the ecosystem. We also detect different candidate members of the crAss-like phage family as well as their bacterial hosts showing that these elusive phages infect different genus of Bacteroidetes. This work opens the door to single sample analysis and concomitant study of phages and bacteria in complex communities.

Immune responses are conditioned by host genetics as well as environmental stimuli that include disease-causing pathogens but also a diverse community of commensal micro-organisms (bacteria, fungi, viruses). However, we still have little information on how immune reactivity is regulated in normal healthy humans. Knowledge in this arena is critical since it could lead to experimental approaches that might impact on the amplitude and duration of immune responses against pathogenic infections. A better understanding of the regulation of mucosal responsiveness can have a major impact on the development and implementation of future vaccine candidates as well as the regulation of systemic diseases, including metabolic, allergic, autoimmune, and psychiatric disorders, which are now suggested to be associated with the perturbation of the normal commensal microbiota.

Leishmania genomic adaptation during sand fly infection is only poorly understood. In particular, the possibility of allelic selection in a given parasite population inside the insect vector has not been investigated, even though sexual recombination and the possibly of self-sex (selfing) can change allele frequencies and thus may be relevant for parasite transmission and virulence. We investigate this important open question conducting experimental sand fly infection with bona fide amastigotes isolated from infected hamster spleen, and derived promastigotes with different karyotypic profiles. Applying our genome instability pipeline (GIP) on sand fly-recovered parasites revealed a novel form of Leishmania genome instability inside the insect vector relying on gene conversion, which causes haplotype shuffling and likely allows for the selection of beneficial alleles.