Gut microbiota and the immune system are in constant exchange shaping both host immunity and microbial communities. Here, improper immune regulation can cause inflammatory bowel disease (IBD) and colitis. Antibody therapies blocking signaling through the CD40–CD40L axis showed promising results as these molecules are deregulated in certain IBD patients. To better understand the mechanism, we used transgenic DC-LMP1/CD40 animals with a constitutive CD40-signal in CD11c + cells, causing a lack of intestinal CD103 + dendritic cells (DCs) and failure to induce regulatory T (iTreg) cells. These mice rapidly develop spontaneous fatal colitis, accompanied by dysbiosis and increased inflammatory IL-17 + IFN-γ + Th17/Th1 and IFN-γ + Th1 cells. In the present study, we analyzed the impact of the microbiota on disease development and detected elevated IgA- and IgG-levels in sera from DC-LMP1/CD40 animals. Their serum antibodies specifically bound intestinal bacteria, and by proteome analysis, we identified a 60 kDa chaperonin GroEL (Hsp60) from Helicobacter hepaticus ( Hh ) as the main specific antigen targeted in the absence of iTregs. When re-derived to a different Hh -free specific-pathogen-free (SPF) microbiota, mice showed few signs of disease, normal microbiota, and no fatality. Upon recolonization of mice with Hh , the disease developed rapidly. Thus, the present work identifies GroEL/Hsp60 as a major Hh -antigen and its role in disease onset, progression, and outcome in this colitis model. Our results highlight the importance of CD103 + DC- and iTreg-mediated immune tolerance to specific pathobionts to maintain healthy intestinal balance.

Colorectal cancer is one of the most common cancers and a major cause of mortality. Proinflammatory and antitumor immune responses play critical roles in colitis-associated colon cancer. CCL17, a chemokine of the C-C family and ligand for CCR4, is expressed by intestinal dendritic cells in the steady state and is upregulated during colitis in mouse models and inflammatory bowel disease patients. In this study, we investigated the expression pattern and functional relevance of CCL17 for colitis-associated colon tumor development using CCL17–enhanced GFP-knockin mice. CCL17 was highly expressed by dendritic cells but also upregulated in macrophages and intermediary monocytes in colon tumors induced by exposure to azoxymethane and dextran sodium sulfate. Despite a similar degree of inflammation in the colon, CCL17-deficient mice developed fewer tumors than did CCL17-competent mice. This protective effect was abrogated by cohousing, indicating a dependency on the microbiota. Changes in microbiota diversity and composition were detected in separately housed CCL17-deficient mice, and these mice were more susceptible to azoxymethane-induced early apoptosis in the colon affecting tumor initiation. Immune cell infiltration in colitis-induced colon tumors was not affected by the lack of CCL17. Taken together, our results indicate that CCL17 promotes colitis-associated tumorigenesis by influencing the composition of the intestinal microbiome and reducing apoptosis during tumor initiation.

African clawed frogs are common animal models used in various research areas. However, husbandry and especially feeding regimens are not nearly as standardized as is established for other laboratory animals. We recorded the diets and feeding protocols commonly used in laboratory practice in a questionnaire (18 responses). The survey revealed a wide variety of housing conditions. Feeding protocols and, in particular, diet composition varied considerably between facilities. While diets tailored to Xenopus were used in the majority, differences in feeding frequency and dietary components were noted. From five responses, the weekly feed intake per frog could be calculated, showing considerable differences in dry matter intake (1.37–5.4 g). The labelled nutrient content of the diets fed in the facilities (n = 10) met the recommendations in most cases, with protein as the major energy source. However, the mineral content varied markedly between diets. Both floating and sinking diets were used, while quickly sinking diets were associated with feed leftovers. Feed processing may likely influence feed intake behavior. Further research is needed to ensure standardization for aquatic species with respect to husbandry systems, feeding regimens, and especially the nutrient composition of feeds. Furthermore, this work will contribute positively to animal welfare and the comparability of research results.

Acid base homeostasis and urine pH is influenced by the dietary cation anion balance (DCAB) in many species. Here, a negative DCAB acidifies the urine, while higher DCABs alkalize the urine. The dimension of the DCAB effect can be species-specific, because of differences in urine buffer systems. The aim of the present study was to describe the response of laboratory mice to diets with different DCAB. We used 8-week-old wildtype male mice of the C57Bl/6J inbred strain and CD1 outbred stock. Three groups (n = 15 animals/group) were formed and fed standard diet A for adaptation. For the 7-week feeding trial, mice were either kept on diet A (DCAB −7 mmol/kg dry matter (DM) or switched to diet B (246 mmol/kg DM) or C (−257 mmol/kg DM). Urine pH was measured weekly from a pooled sample per cage. There was a significant difference in the basal urine pH on diet A between C57Bl6/J and CD1 mice. The shift in urine pH was also significantly different between the two groups investigated.

The major responsibility of researchers and laboratory animal facilities is to ensure animal well-being during the time of acclimatization, experiments, and recovery. In this context, animal housing conditions are of utmost importance. Here, we implemented a mobile and modular floor-pen housing system for laboratory rabbits that combines rabbits’ natural behavioral requirements and the high hygiene standards needed in biomedical science. Twelve female New Zealand White (NZW) rabbits were single- or group-housed for 12 months in mobile and modular floor-pens. Their general health status was evaluated at the end of the experimental setup. Further, we performed behavioral analysis of six additional NZW females group-housed for eight weeks in pens of two different sizes. We show that our improved housing concept supported species-specific behavioral patterns. Taken together, our housing system provides an optimal setup for rabbits in animal facilities that combines strict requirements for animal experiments with animal welfare.