Biology subjects

Treichel, N.

Publications and source records attributed to Treichel, N..

6 recordsLinked to original sources

bioRxiv2026

Macrophage renewal in the small intestine governs early-life control of streptococci

Group B Streptococcus (GBS) is both a common intestinal colonizer that is transmitted intergenerationally, and a primary cause of neonatal sepsis worldwide. However, the innate immune mechanisms that restrict the pathogen at the intestinal barrier early in life remain poorly understood. Using an enteral GBS-colonization model in infant mice, we found that lamina-propria (LP) macrophages controlled both GBS-colonization densities and invasion in an age-dependent fashion. LP macrophages turnover and differentiation were strongly impacted by topology. In the small intestine, monocytes infiltration of the LP occurred from birth on in response to perinatally acquired microbiota, whereas in the colon it was driven by the weaning reaction. Moreover, macrophages of the small intestine mounted a robust, MyD88-dependent inflammatory response to GBS, while those of the colon remained largely unaffected. Together, these findings demonstrate that region-specific macrophage dynamics early in life critically influence host-pathogen-interactions during GBS-colonization.

immunology↗

bioRxiv2025

The adhesion molecules β7 integrin and L-selectin contribute to cholestatic liver disease in male mice

Background & AimsPrimary sclerosing cholangitis (PSC) is a long-term progressive disease, often occurring in conjunction with inflammatory bowel disease (IBD). Dysregulated immune cell migration and gut microbiota alterations are implicated in disease progression. Livers of PSC patients show upregulation of the endothelial ligand mucosal addressin cell-adhesion molecule-1 (MAdCAM-1). Here we examined the role of the leukocytic adhesion molecules (AM) {beta}7 integrin and L-selectin, both binding partners of MAdCAM-1, in an experimental mouse model resembling aspects of human PSC. MethodsWild type (WT), {beta}7 integrin-deficient ({beta}7-/-), L-selectin-deficient (L-sel-/-), and L-selectin/{beta}7 integrin double-deficient (L-sel-/-/{beta}7-/-) male mice were compared in the model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy. The extent of pathology was evaluated by serum parameters, histology, flow cytometry, and expression of inflammatory mediators. Fecal microbiota changes were assessed by 16S rRNA amplicon sequencing and intestinal permeability was measured by FITC-dextran assay. ResultsAM-deficient mice were markedly protected from DDC-induced cholangiopathy. Hepatic immune cell populations of AM-deficient mice differed significantly from those of WT mice. Adoptively transferred {beta}7-/- CD8+ T cells caused significantly less liver damage than CD8+ WT T cells in DDC-treated {beta}7-/- mice. DDC-feeding caused substantial changes in fecal microbiota profiles, which differed between the mouse strains, and a strong increase in intestinal permeability that was significantly lower in {beta}7-/- than WT mice. Conclusions{beta}7 integrin and L-selectin contribute to DDC-induced cholangiopathy with {beta}7 integrin-expressing CD8+ T cells playing a crucial role in promoting pathogenesis. In addition, AM-expressing immune cells may contribute to the inflammatory process by causing unfavorable gut microbiota shifts and destabilizing the gut barrier. Synopsis{beta}7 integrin- and/or L-selectin-deficient mice are less susceptible to 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced experimental cholangiopathy. {beta}7 integrin-expressing CD8+ T cells contribute to DDC-induced pathogenesis. {beta}7 integrin promotes DDC-induced gut barrier dysfunction and microbiota shifts, potentially exacerbating hepatic injury.

immunology↗

bioRxiv2024

Broad diversity of human gut bacteria accessible via a traceable strain deposition system

Numerous bacteria in the human gut microbiome remain unknown and/or have yet to be cultured. While collections of human gut bacteria have been published, few strains have been made publicly available. A major hurdle in making strains publicly available is their deposition to public culture collections. We propose a framework for the bulk-deposition of strains to culture collections, which removes many of the barriers previously identified (www.dsmz.de/bulk-deposit). Using this bulk-deposition system we have created a publicly available collection of human gut isolates. The Human intestinal Bacteria Collection (HiBC) (www.hibc.rwth-aachen.de) contains 340 strains representing 198 species within 29 families and 7 phyla, of which 29 previously unknown species are taxonomically described and named. These included two butyrate-producing species of Faecalibacterium and new dominant species associated with health and inflammatory bowel disease, Ruminococcoides intestinale and Blautia intestinihominis, respectively. Plasmids were prolific within the HiBC isolates, with almost half (46%) of strains containing plasmids, with a maximum of six within a strain. This included a broadly occurring plasmid (pBAC) that exists in three diverse forms across Bacteroidales species. Megaplasmids were identified within two strains, the pMMCAT megaplasmid is globally present within multiple Bacteroidales species. This collection of easily searchable and publicly available gut bacterial isolates will facilitate functional studies of the gut microbiome.

microbiology↗

bioRxiv2023

Secondary bile acid production by gut bacteria promotes Western diet-associated colorectal cancer

Western diet is an important risk factor for the development of sporadic colorectal cancer (CRC). Dietary fat stimulates bile acid (BA) production by the host and their conversion to secondary BAs by 7-dehydroxylating (7DH+) bacteria, but causal proof of their tumor-promoting effects in vivo is lacking. To address this, we performed feeding studies in a genetically engineered pig model of CRC combined with multi-omics analyses and gnotobiotic mouse studies. Western diet worsened the disease phenotype in APC1311/+ pigs. This was accompanied by microbiota changes, increased levels of the secondary bile acid deoxycholic acid (DCA), and higher colonic epithelial cell proliferation. The latter was counteracted by using the BA-scavenging drug colestyramine. Metagenomic analysis across multiple cohorts revealed higher occurrence of bai (BA inducible) operons from Clostridium scindens and close relatives in stool of CRC subjects (n = 1,034). Using two gnotobiotic mouse models of CRC, we demonstrate that colonization with 7DH+ bacteria (C. scindens or Extibacter muris) increased colonic tumor loads. This work provides clear evidence for the causal role of microbiome-derived DCA production in CRC under detrimental dietary conditions, opening avenues for future preventive strategies.

microbiology↗

bioRxiv2022

Enhanced cultured diversity of the mouse gut microbiota enables custom-made synthetic communities

Microbiome research is hampered by the fact that many bacteria are still unknown and by the lack of publicly available isolates. Fundamental and clinical research is in need of comprehensive and well-curated repositories of cultured bacteria from the intestine of mammalian hosts. In this work, we expanded the mouse intestinal bacterial collection (www.dsmz.de/miBC) to 212 strains, all publicly available and taxonomically described. This includes the study of strain-level diversity, small-sized bacteria, and the isolation and characterization of the first cultured members of one novel family, 10 novel genera, and 39 novel species. We demonstrate the value of this collection by performing two studies. First, metagenome-educated design allowed establishing custom synthetic communities (SYNs) that reflect different susceptibilities to DSS-induced colitis. Second, nine phylogenetically and functionally diverse species were used to amend the Oligo-Mouse Microbiota (OMM)12 model [Brugiroux et al. 2016 Nat Microbiol]. These strains compensated for differences observed between gnotobiotic OMM12 and specific pathogen-free (SPF) mice at multiple levels, including body composition and immune cell populations (e.g., T-cell subtypes) in the intestine and associated lymphoid tissues. Ready-to-use OMM stocks are available to the community for use in future studies. In conclusion, this work improves our knowledge of gut microbiota diversity in mice and enables functional studies via the modular use of isolates.

microbiology↗

bioRxiv2022

Neonatal Peyer's patch cDC activation as a pacemaker of postnatal immune maturation

Marked differences exist between the mucosal immune system of the neonate and adult host. The pronounced influence of the enteric microbiota in adults suggests a causal relationship between postnatal colonization and immune maturation. However, using metagenomic, metaproteomic, and functional immunological analyses we demonstrate an early presence of bacteria and immunogenic microbial antigens preceding immune maturation in the small intestine, the primary inductive site of intestinal immunity. Instead, transcriptomic, flow cytometric and histological analysis indicated neonatal Peyers patch (PP) mononuclear phagocytes (MNP) as rate limiting factor of postnatal immune maturation. Despite the early presence of MNPs, conventional dendritic cells (cDC) of type 1, 2a and 2b exhibited significant age-dependent differences in tissue distribution and cellular composition. Single cell transcriptional profiling and functional assays revealed decreased antimicrobial and antigen processing/presentation capacity, an overall retarded cell maturation and reduced antigen uptake. In cDC2a this resulted in a reduced proportion of CCR7+ migratory cells and a consequent defect in CD4 T cell priming. Interestingly, transcriptional profiling of neonatal DC subsets identified reduced expression of type I interferon (IFN)-stimulated genes (ISG). Type I IFN induction by oral administration of the TLR7 agonist R848 accelerated MNP maturation and enhanced cognate antigen CD4 T cell priming. However, humoral responses to oral vaccination in the presence of R848 were significantly reduced. Together, our results identify PP MNP maturation as pacemaker of postnatal mucosal immune priming, indicate the biological role of delayed maturation and demonstrate that targeted interventional strategies allow manipulation of mucosal responses in early life.

immunology↗