Highlights d Dysbiosis can lead to increased colon tumor susceptibility and CD8 + IFNg + T cells d Increased colon CD8 + IFNg + T cells are associated with more inflammation and tumors d Dysbiosis and increased tumorigenesis are associated with greater T cell exhaustion

No abstract

Thermosensitive transient receptor potential V3 (TRPV3) is a polymodal receptor implicated in nociceptive, thermoceptive, pruritoceptive, and inflammatory pathways. Reports focused on understanding the role of TRPV3 in thermoception or nociception are not conclusive. Previous studies also show that aberrant hyperactivity of TRPV3 channels results in spontaneous itch and dermatitis-like symptoms, but the resultant behavior is highly dependent on the background of the animal and the skin microbiome. To determine the function of hyperactive TRPV3 channels in somatosensory sensations, we tested different somatosensory behaviors using a genetic mouse model that carries a gain-of-function point mutation G573S in the Trpv3 gene (Trpv3G573S). Here we report that Trpv3G573S mutants show reduced perception of cold, acetone-induced cooling, punctate, and sharp mechanical pain. By contrast, locomotion, noxious heat, touch, and mechanical itch are unaffected in Trpv3G573S mice. We fail to observe any spontaneous itch responses and/or dermatitis in Trpv3G573S mutants under specific pathogen (Staphylococcus aureus)-free conditions. However, we find that the scratching events in response to various pruritogens are dramatically decreased in Trpv3G573S mice in comparison to wild-type littermates. Interestingly, we observe sensory hypoinnervation of the epidermis in Trpv3G573S mutants, which might contribute to the deficits in acute mechanical pain, cool, cold, and itch sensations.

Objectives Sulforaphane is a bioactive metabolite with anti-inflammatory activity that is derived from glucosinolates, which are highly abundant in cruciferous vegetables including broccoli sprouts. There have been limited studies to investigate a whole foods approach to increase sulforaphane levels with therapeutic effect and reduce inflammation. In the current study, using a mouse model of inflammatory bowel disease, we aimed to investigate the ability of steamed broccoli sprouts to ameliorate colitis and the role of the microbiota in mediating any effects. Methods C57BL/6J male mice were fed base diet or 5% steamed broccoli sprout diet for 2 weeks prior to induction of colitis with 2–3% DSS (5–7 days) and kept on their respective diets until sacrifice. Body weight and disease activity index scores were recorded daily, and histological assessment was performed on H&E sections of colon. Urine, feces, blood, and GI tract tissues and intestinal content were collected for LC-MS/MS quantification of sulforaphane and glucoraphanin. The 16S rRNA sequencing was performed to analyze gut microbiome. Germ-free mice were fed base diet or 5% steamed broccoli sprout diet for 2 weeks followed by treatment with 5 days of DSS to determine the role of gut microbiota in mediating the anti-inflammatory effects of the steamed broccoli sprout diet. Results We observed that despite inactivation of the plant myrosinase enzyme responsible for the generation of sulforaphane via steaming, measurable levels of sulforaphane were detectable in the colon tissue and feces of mice after ingestion of steamed broccoli sprouts. In addition, this preparation of broccoli sprouts was also capable of reducing chemically-induced colitis. This protective effect was dependent on the presence of an intact gut microbiota, highlighting an important role for the microbiota in the metabolism of cruciferous vegetables to generate bioactive metabolites and promote their anti-inflammatory effects. Conclusions Altogether, these results suggest that the incorporation of a steamed broccoli sprouts diet is a viable dietary intervention to complement current medical therapies for patients with inflammatory bowel disease. Funding Sources This work was supported by USDA-NIFA-AFRI Foundational Program [Grant No. 2018–67,017-27,520].

No abstract