Genetic and environmental factors shape host susceptibility to infection, but how and how rapidly environmental variation might alter the susceptibility of mammalian genotypes remains unknown. Here, we investigate the impacts of seminatural environments upon the nematode susceptibility profiles of inbred C57BL/6 mice. We hypothesized that natural exposure to microbes might directly (e.g., via trophic interactions) or indirectly (e.g., via microbe-induced immune responses) alter the hatching, growth, and survival of nematodes in mice housed outdoors. We found that while C57BL/6 mice are resistant to high doses of nematode (Trichuris muris) eggs under clean laboratory conditions, exposure to outdoor environments significantly increased their susceptibility to infection, as evidenced by increased worm burdens and worm biomass. Indeed, mice kept outdoors harbored as many worms as signal transducer and activator of transcription 6 (STAT6) knockout mice, which are genetically deficient in the type 2 immune response essential for clearing nematodes. Using 16S ribosomal RNA sequencing of fecal samples, we discovered enhanced microbial diversity and specific bacterial taxa predictive of nematode burden in outdoor mice. We also observed decreased type 2 and increased type 1 immune responses in lamina propria and mesenteric lymph node (MLN) cells from infected mice residing outdoors. Importantly, in our experimental design, different groups of mice received nematode eggs either before or after moving outdoors. This contrasting timing of rewilding revealed that enhanced hatching of worms was not sufficient to explain the increased worm burdens; instead, microbial enhancement and type 1 immune facilitation of worm growth and survival, as hypothesized, were also necessary to explain our results. These findings demonstrate that environment can rapidly and significantly shape gut microbial communities and mucosal responses to nematode infections, leading to variation in parasite expulsion rates among genetically similar hosts.

This is the first description of the mcr-1 gene in Shigella, which is atypical given that colistin is not ordinarily used to treat diarrhoea. Our data suggest the mcr-1 gene has been circulating in human-restricted pathogens for some time but likely carries a selective fitness cost.

Data Availability All raw genomic data that support the findings of this study have been deposited in the European Nucleotide Archive (project: PRJEB30967) and can be accessed via this link (https://www.ebi.ac.uk/ena/data/search?query=PRJEB30967). Details about accession numbers of S. sonnei isolates can be found in Supplementary Table 1. The S. sonnei reference genome Ss046 chromosome (accession number: NC_007382), virulence plasmid pSs046 (accession number: NC_007385.1) and three small plasmids commonly found in global lineage III S. sonnei: spA (accession number: NC_009345.1), spB (accession number: NC_009346.1), and spC (accession number: NC_009347.1) were downloaded from GenBank. Raw MinION reads for plasmid p01_0123 are deposited in ENA (accession number: ERS3050922). Source data for main figures [Figs. 2a, 3a, 4] and Extended Data [ED Figs. 1, 2] are provided with the paper. Additional data that support the findings of this study are available from the corresponding author upon request. Author contributions PTD, MAR, and SB designed the study. PTD performed data analysis and interpreted the results under the scientific guidance of MAR and SB. PTD drafted the paper, with MAR and SB revising and structuring the paper. PTD and HNDT performed whole genome sequencing. PTD and TNTN performed plasmid isolation, digestion and sequencing. PTD, FA, and TNTN performed the plasmid conjugation experiments. HTT performed basic microbiology work. HCT and CB assisted in the design of laboratory experiments. DVT recruited patients and performed the clinical work required for the study. HCT, CB, and GET contributed to the editing of the paper. All authors read and approved the final draft.