Sex differences in pain-related behaviors and clinical progression of disease in mouse models of visceral pain

Previous studies have reported sex differences in irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) patients, including differences in visceral pain perception. Despite this, sex differences in behavioral manifestations of visceral pain and underlying pathology of the gastrointestinal tract have been largely understudied in preclinical research. In this study, we evaluated potential sex differences in spontaneous visceral nociceptive responses, referred abdominal hypersensitivity, disease progression and bowel pathology in mouse models of acute and persistent colon inflammation. Our experiments show that females exhibit more visceral nociceptive responses and referred abdominal hypersensitivity than males in the context of acute but not persistent colon inflammation. We further demonstrate that, following acute and persistent colon inflammation, visceral pain-related behavioral responses in females and males are distinct, with increases in licking of the abdomen only observed in females and increases in abdominal contractions only seen in males. During persistent colon inflammation, males exhibit worse disease progression than females, which is manifested as worse physical appearance and higher weight loss. However, no measurable sex differences were observed in persistent inflammation-induced bowel pathology, stool consistency or fecal blood. Overall, our findings demonstrate that visceral pain-related behaviors and disease progression in the context of acute and persistent colon inflammation are sex-dependent, highlighting the importance of considering sex as a biological variable in future mechanistic studies of visceral pain as well as in the development of diagnostics and therapeutic options for chronic gastrointestinal diseases.

Increasing Intestinal Soy Protein Hydrolysate Levels Promotes Colon Inflammation By Affecting Microbial Metabolism and Increases the Protein Expression of Colonic Tight Junction Proteins

Background Increasing intestinal protein levels change the colonic microbial community and metabolic profile of pigs, but the effect of this on colonic inflammation and barrier function in growing pigs remains unclear. Results Sixteen pigs (35.2 ± 0.3 kg) were infused with sterile saline (control) or soy protein hydrolysate (SPH) (70 g/day) through a duodenal fistula twice daily during a 15-day experimental period. The SPH treatment did not affect their average daily feed intake and daily weight gain (P > 0.05), but reduced colon index and length (P < 0.05). Illumina MiSeq sequencing revealed that species richness was increased following SPH intervention (P < 0.05). Furthermore, SPH reduced the abundance of butyrate- and propionate-producing bacteria—such as Lachnospiraceae NK4A136 group, Lachnospiraceae_uncultured, Coprococcus 3 Lachnospiraceae UCG-002, and Anaerovibrio—and increased the abundance of potentially pathogenic bacteria and protein-fermenting bacteria, such as Escherichia-Shigella, Dialister, Veillonella, Prevotella, Candidatus Saccharimonas, Erysipelotrichaceae UCG-006, Prevotellaceae_uncultured, and Prevotellaceae UCG-003 (P < 0.05). In addition, a lower content of total short-chain fatty acids, propionate, and butyrate and a higher concentration of cadaverine, putrescine, total biogenic amines, ammonia, and isovalerate were observed following SPH infusion (P < 0.05). Further analysis revealed that SPH increased the concentration of tumour necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-8 in the colonic mucosa (P < 0.05). Interestingly, SPH intervention increased the expression of occluding, zonula occludens (ZO)-1, and claudin-1 in colonic mucosa (P < 0.05). Correlation analysis showed that different genera were significantly related to the production of metabolites and the concentrations of pro-inflammatory cytokines. Conclusion Overall, increasing intestinal soy protein levels altered the colonic microbial composition and metabolic profile, which may lead to colon inflammation and may also strengthen the colon barrier function.

Bringing to Light the Risk of Colorectal Cancer in Inflammatory Bowel Disease: Mucosal Glycosylation as a Key Player

Colitis-associated cancer is a major complication of inflammatory bowel disease remaining an important clinical challenge in terms of diagnosis, screening, and prognosis. Inflammation is a driving factor both in inflammatory bowel disease and cancer, but the mechanism underlying the transition from colon inflammation to cancer remains to be defined. Dysregulation of mucosal glycosylation has been described as a key regulatory mechanism associated both with colon inflammation and colorectal cancer development. In this review, we discuss the major molecular mechanisms of colitis-associated cancer pathogenesis, highlighting the role of glycans expressed at gut epithelial cells, at lamina propria T cells, and in serum proteins in the regulation of intestinal inflammation and its progression to colon cancer, further discussing its potential clinical and therapeutic applications.

Combined Rg1 and adipose-derived stem cells Alleviate DSS-induced colitis in a mouse model

Background Inflammatory bowel diseases (IBDs) including Crohn's disease and ulcerative colitis are chronic inflammatory disorders that can affect the entire gastrointestinal tract and the colonic mucosa, no medical or surgical cure for IBD, and all have side effects that limit their use, exhibit a high necessity for new therapeutic strategies. Adipose-derived stem cells (ADSC) therapy represents a promising option for the treatment of IBD. Rg1 Previous study indicated that ginsenoside (Rg1) can ameliorate inflammatory disease such as colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg imbalance [1]. In this study, we investigated whether Rg1 can enhance the effect of ADSC on DSS-induced colitis in a mouse model. Methods Mice with dextran sulfate sodium-induced colitis were injected intravenously with ADSC and administered with Rg1 by gavage. Body weight change, colon length, H&E staining were used to evaluate colon inflammation severity in a DSS-induced colitis Serum were collected for Cytokine detection by ELISA. The proportion and FMI of immune cells in spleen were analyzed by flow cytometry. Stool DNA was extracted for 16S rRNA gene sequencing. Results Rg1 and ADSC showed significantly ameliorated colon inflammation, such as body weight loss, shortening of colon length, histology score. Rg1 and ADSC treatment downregulated the level of proinflammatory cytokines, including IL-1β, TNF-α, IL-6, IL-4 and IL-17A and upregulated the immunosuppressive cytokine IL-10 in serum. We observed that the structure of the microbial community in Rg1 + ADSC group were significantly changed compared to that of ADSC and Rg1 groups, respectively. Additionally, Rg1 and ADSC treated selectively upregulated the percentage of spleen regulatory T (Treg) cells as well as downregulated the frequency of T helper type 17 (Th17) cells, ameliorating the Treg/Th17 balance to maintain intestinal homeostasis. Furthermore, we found the combination of ADSC + Rg1 groups showed more efficiently than that of ADSC and Rg1 alone, respectively, which indicates that the regulation effect of Rg1 on gut microbiome may enhance the effects of ADSCs in restoring immune balance. Conclusions Our study indicated that the combination of Rg1 and ADSC can alleviate dextran sulfate sodium-induced colitis more efficiently than that of ADSC alone, Rg1 can enhance the effect of ADSC on DSS-induced colitis in a mouse model.