Project description:The spatial organization of gut microbiome is essential for their interactions with the host. Recently, microbiota alteration in ileum is getting the increasing recognition due to the close interplay with inflammatory diseases and the tumor immunosurveillance. However, how ileal microbiome is spatially regulated remains unclear. Here, we show that DNA-damaging chemotherapy specifically remodels microbiota in ileal mucosa, resulting in the overgrowth of local family Lachnospiraceae that promotes antitumor immunity and synergizes with immune checkpoint blockage. Mechanistically, the prominent proliferative state of transit amplifying cells (TACs) in the ileal crypt presents a vulnerability to chemotherapy-caused genomic stress, resulting in the accumulation of cytosolic dsDNA that subsequently activates AIM2 inflammasome. AIM2-dependent production of IL18 boosts Th1 immunity in ileal lamina propria, which further impairs the antimicrobial host defense of proximal Paneth cells via activating IFN-γ-JAK-STAT signaling. Our findings demonstrate that AIM2 inflammasome shapes ileal microbiome via governing the compartmentalized cellular interplay in ileal crypt, providing mechanistic insights into the regulation of gut biogeography and implicating therapeutic strategies of spatial microbiome intervention using chemotherapy.
Project description:In this study, to unravel the influence of phylogenetic divergence and biogeography in shaping the composition and activity of Daboia venoms, we comparatively investigated the venoms of D. russelii from western India and D. palaestinae from Israel.
Project description:Peanut (Arachis hypogaea) has a large (~2.7 Gbp) allotetraploid genome with closely related component genomes making its genome very challenging to assemble. Here we report genome sequences of its diploid ancestors (A. duranensis and A. ipaënsis). We show they are similar to the peanutâs A- and B-genomes and use them use them to identify candidate disease resistance genes, create improved tetraploid transcript assemblies, and show genetic exchange between peanutâs component genomes. Based on remarkably high DNA identity and biogeography, we conclude that A. ipaënsis may be a descendant of the very same population that contributed the B-genome to cultivated peanut. Whole Genome Bisulphite Sequencing of the peanut species Arachis duranensis and Arachis ipaensis.
Project description:We found that mainstream cigarette smoking (4 cigarettes/day, 5 days/week for 2 weeks using Kentucky Research Cigarettes 3R4F) resulted in >20% decrease in the percentage of normal Paneth cell population in Atg16l1 T300A mice but showed minimal effect in wildtype littermate control mice, indicating that Atg16l1 T300A polymorphism confers sensitivity to cigarette smoking-induced Paneth cell damage. We performed cohousing experiments to test if Paneth cell phenotype is horizontally transmissible as is microbiota. Atg16l1 T300A and littermate controls that were exposed to cigarette smoking were used as microbiota donors, and these donor mice were exposed to smoking for 2 weeks prior to cohousing. Separate groups of Atg16l1 T300A and littermate controls that were not exposed to cigarette smoking were used as microbiota recipients. The microbiota recipients were co-housed with microbiota donors of the same genotype for 4 weeks, during this period the donors continued to be exposed to cigarette smoking. Cigarette smoking was performed using smoking chamber with the dosage and schedule as described above. At the end of the experiment, the fecal microbiota composition was analyzed by 16S rRNA sequencing.
Project description:We applied numerical ecology methods to data produced with a human intestinal tract-specific phylogenetic microarray (the Aus-HIT Chip) to examine the biogeography of mucosa-associated bacteria along the human colon. The microbial DNA associated with matched biopsy tissue samples taken from the cecum, transverse colon, sigmoid colon and rectum of 10 healthy patients was examined. Consistent with previous studies, the profiles revealed a marked inter-subject variability; however, the numerical ecology methods of analysis allowed the subtraction of the subject effect from the data and revealed, for the first time, evidence of a longitudinal gradient for specific microbes along the colorectum: with Streptococcus, Comamonadaceae, Enterococcus and Lactobacillus in greatest abundance at the cecum, with a gradual decline in their relative abundance through to the rectum. Conversely, the analyses suggest that members of the Enterobacteriaceae increase in relative abundance towards the rectum. These differences were validated by quantitative PCR. We were also able to identify significant differences in the profiles, especially for the Streptococci, on the basis of gender. The results derived by these multivariate analyses are biologically intuitive, and suggestive that the biogeography of the colonic mucosa can be monitored for changes via cross-sectional and/or inception cohort studies.
Project description:We profiled transcriptome and accessible chromatin landscapes in intestinal epithelial cells (IECs) from mice reared in the presence or absence of microbiota. We show that regional differences in gene transcription along the intestinal tract were accompanied by major alterations in chromatin organization. Surprisingly, we discovered that microbiota modify host gene transcription in IECs without significantly impacting the accessible chromatin landscape. Instead, microbiota regulation of host gene transcription might be achieved by differential expression of specific TFs and enrichment of their binding sites in nucleosome depleted CRRs near target genes. Our results suggest that the chromatin landscape in IECs is pre-programmed by the host in a region-specific manner to permit responses to microbiota through binding of open CRRs by specific TFs. mRNA and accessible chromatin (DNase-seq) profiles from colonic and ileal IECs were compared between conventionally-raised (CR), germ-free (GF), and conventionalized (CV) C57BL/6 mice.