Biology subjects

Rapin, A.

Publications and source records attributed to Rapin, A..

3 recordsLinked to original sources

bioRxiv2023

Genetic and dietary modulators of the inflammatory response in the gastro-intestinal tract of the BXD mouse genetic reference population

Inflammatory gut disorders, including inflammatory bowel disease (IBD), can be impacted by dietary, environmental and genetic factors. While the incidence of IBD is increasing worldwide, we still lack a complete understanding of the gene-by-environment interactions underlying inflammation and IBD. Here, we profiled the colon transcriptome of 52 BXD mouse strains fed with a chow or high-fat diet (HFD) and identified a subset of BXD strains that exhibit an IBD-like transcriptome signature on HFD, indicating that an interplay of genetics and diet can significantly affect intestinal inflammation. Using gene co-expression analyses, we identified modules that are enriched for IBD-dysregulated genes and found that these IBD-related modules share cis-regulatory elements that are responsive to the STAT2, SMAD3, and REL transcription factors. We used module quantitative trait locus (ModQTL) analyses to identify genetic loci associated with the expression of these modules. Through a prioritization scheme involving systems genetics in the mouse and integration with external human datasets, we identified Muc4 and Epha6 as the top candidates mediating differences in HFD-driven intestinal inflammation. This work provides insights into the contribution of genetics and diet to IBD risk and identifies two candidate genes, MUC4 and EPHA6, that may mediate IBD susceptibility in humans.

systems biology↗

bioRxiv2020

A prevalent and culturable microbiota links ecological balance to clinical stability of the human lung after transplantation

There is accumulating evidence that the lower airway microbiota impacts lung health. However, the link between microbial community composition and lung homeostasis remains elusive. We combined amplicon sequencing and culturomics to characterize the viable bacterial community in 234 longitudinal bronchoalveolar lavage samples from 64 lung transplant recipients and established links to viral loads, host gene expression, lung function, and transplant health. We find that the lung microbiota post-transplant can be categorized into four distinct compositional states, pneumotypes. The predominant balanced pneumotype was characterized by a diverse bacterial community with moderate viral loads, and host gene expression profiles suggesting immune tolerance. The other three pneumotypes were characterized by being either microbiota-depleted, or dominated by potential pathogens, and were linked to increased immune activity, lower respiratory function, and increased risks of infection and rejection. Collectively, our findings establish a link between the lung microbial ecosytem, human lung function, and clinical stability post-transplant. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=191 SRC="FIGDIR/small/106211v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@1df2be3org.highwire.dtl.DTLVardef@ba839dorg.highwire.dtl.DTLVardef@116f657org.highwire.dtl.DTLVardef@86d8ac_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2019

Infection with a small intestinal helminth Heligmosomoides polygyrus bakeri consistently alters microbial communities throughout the small and large intestine

Increasing evidence suggests that intestinal helminth infection can alter intestinal microbial communities with important impacts on the mammalian host. However, all of the studies to date utilize different techniques to study the microbiome and access different sites of the intestine with little consistency noted between studies. In the present study, we set out to perform a comprehensive analysis of the impact of intestinal helminth infection on the mammalian intestinal bacterial microbiome. For this purpose, we investigated the impact of experimental infection using the natural murine small intestinal helminth, Heligmosomoides polygyrus bakeri (Hpb) and examined possible alterations in both the mucous and luminal bacterial communities along the entire small and large intestine. We also explored the impact of common experimental variables, including the parasite batch and pre-infection microbiome, on the outcome of helminth-bacterial interactions. This work provides evidence that helminth infection reproducibly alters intestinal microbial communities - with an impact of infection noted along the entire length of the intestine. Although the exact nature of helminth-induced alterations to the intestinal microbiome differed depending on the parasite batch and microbiome community structure present prior to infection, changes extended well beyond the introduction of new bacterial species by the infecting larvae. Moreover, striking similarities between different experiments were noted, including the consistent outgrowth of a bacterium belonging to the Peptostreptococcaceae family throughout the intestine.\n\nAuthor SummaryIncreasing evidence indicates a role for interactions between intestinal helminths and the microbiome in regulating mammalian health, and a greater understanding of helminth-microbiota interactions may open the path for the development of novel immunomodulatory therapies. However, such studies are hampered by the inconsistent nature of the data reported so far. Such inconsistancies likely result from variations in the experimental and technological methodologies employed to investigate helminth-microbiota interactions and well has natural variation in the starting microbiome composition and/or worm genetics. We conducted a thorough study in which the reproducibility of helminth-induced alterations of microbial communities was determined and impact of common experimental variables - such as the starting microbiome and parasite batch - was determined. Our work reveals the robust ability of small intestinal helminth infection to alter microbial communities along the entire length of the intestine and additionally identifies a single bacterium that is strongly associated with infection across multiple experiments.

microbiology↗