Microbiota and Nutrient Portraits of European Roe Deer (Capreolus capreolus) Rumen Contents in Characteristic Southern German Habitats.

Roe deer (Capreolus capreolus) are found in various habitats, from pure forest cultures to agricultural areas and mountains. In adapting to the geographically and seasonally differentiating food supply, they depend, above all, on an adapted microbiome. However, knowledge about the microbiome of wild ruminants still needs to be improved. There are only a few publications for individual species with a low number of samples. This study aims to identify a core microbiota for Bavarian roe deer and present nutrient and microbiota portraits of the individual habitat types. This study investigated the roe deer's rumen (reticulorumen) content from seven different characteristic Bavarian habitat types. The focus was on the composition of nutrients, fermentation products, and the rumen bacterial community. A total of 311 roe deer samples were analysed, with the most even possible distribution per habitat, season, age class, and gender. Significant differences in nutrient concentrations and microbial composition were identified for the factors habitat, season, and age class. The highest crude protein content (plant protein and microbial) in the rumen was determined in the purely agricultural habitat (AG), the highest value of non-fibre carbohydrates in the alpine mountain forest, and the highest fibre content (neutral detergent fibre, NDF) in the pine forest habitat. Maximum values for fibre content go up to 70% NDF. The proportion of metabolites (ammonia, lactate, total volatile fatty acids) was highest in the Agriculture-Beech-Forest habitat (ABF). Correlations can be identified between adaptations in the microbiota and specific nutrient concentrations, as well as in strong fluctuations in ingested forage. In addition, a core bacterial community comprising five genera could be identified across all habitats, up to 44% of total relative abundance. As with all wild ruminants, many microbial genera remain largely unclassified at various taxonomic levels. This study provides a more in-depth insight into the diversity and complexity of the roe deer rumen microbiota. It highlights the key microorganisms responsible for converting naturally available nutrients of different botanical origins.

"Get the best out of what comes in" - adaptation of the microbiota of chamois (Rupicapra rupicapra) to seasonal forage availability in the Bavarian Alps.

As an inhabitant of the Alps, chamois are exposed to significant climatic changes throughout the year and are also strongly confronted with changing forage availability. Besides horizontal and vertical migratory movements as an adaptation, it undergoes physiological transformations and dynamic changes in the ruminal microbiota. The following study used 48 chamois of different ages and genders to investigate to which extent the ingested food plants, the resulting crude nutrients in the rumen (reticulorumen) contents, and the bacterial microbiota in the rumen and their fermentation products were influenced by the changes over the seasons. Very little is known about the microbiota of wild ruminants, and many bacterial taxa could only be determined to certain taxonomic levels in this study. However, adapted microbiota reflects the significant changes in the ingested forage and the resulting crude nutrients. For some taxa, our results indicated potential functional relationships. In addition, 15 genera were identified, representing almost 90% of the relative abundance, forming the central part of the microbial community throughout the year. The successful and flexible adaptation of chamois is reflected in the chamois rumen's nutrient and microbial profile. This is also the first study that analyzes the microbiota of the chamois using rumen samples and considers the microbiota in a seasonal comparison.

Targeting nucleic acid sensors in tumor cells to reprogram biogenesis and RNA cargo of extracellular vesicles for T cell-mediated cancer immunotherapy.

Tumor-derived extracellular vesicles (EVs) have been associated with immune evasion and tumor progression. We show that the RNA-sensing receptor RIG-I within tumor cells governs biogenesis and immunomodulatory function of EVs. Cancer-intrinsic RIG-I activation releases EVs, which mediate dendritic cell maturation and T cell antitumor immunity, synergizing with immune checkpoint blockade. Intact RIG-I, autocrine interferon signaling, and the GTPase Rab27a in tumor cells are required for biogenesis of immunostimulatory EVs. Active intrinsic RIG-I signaling governs composition of the tumor EV RNA cargo including small non-coding stimulatory RNAs. High transcriptional activity of EV pathway genes and RIG-I in melanoma samples associate with prolonged patient survival and beneficial response to immunotherapy. EVs generated from human melanoma after RIG-I stimulation induce potent antigen-specific T cell responses. We thus define a molecular pathway that can be targeted in tumors to favorably alter EV immunomodulatory function. We propose "reprogramming" of tumor EVs as a personalized strategy for T cell-mediated cancer immunotherapy.

Tumor cell-intrinsic RIG-I signaling governs synergistic effects of immunogenic cancer therapies and checkpoint inhibitors in mice.

Immunogenic cancer therapies, including radiation and hypomethylating agents, such as 5-azacytidine, rely on tumor cell-intrinsic activation of the RNA receptor RIG-I for their synergism with immune checkpoint inhibitors. Possible RIG-I ligands are small nuclear RNA (snRNA) and endogenous retroviral elements (ERV) leaking from the nucleus during programmed cell death.