The impact of type 2 diabetes on long-term gastrointestinal sequelae after colorectal cancer surgery:national population-based study

BACKGROUND: Long-term gastrointestinal sequelae are common after colorectal cancer surgery, but the impact of type 2 diabetes (T2D) is unknown. METHODS: In a cross-sectional design, questionnaires regarding bowel function and quality of life (QoL) were sent to all Danish colorectal cancer survivors, who had undergone surgery between 2001 and 2014 and had more than 2 years follow-up without relapse. The prevalence of long-term gastrointestinal sequelae among colorectal cancer survivors with and without T2D were compared while stratifying for type of surgical resection and adjusting for age, sex, and time since surgery. RESULTS: A total of 8747 out of 14 488 colorectal cancer survivors answered the questionnaire (response rate 60 per cent), consisting of 3116 right-sided colonic, 2861 sigmoid, and 2770 rectal resections. Of these, 690 (7.9 per cent) had a diagnosis of T2D before surgery. Survivors with T2D following rectal resection had a 15 per cent (95 per cent c.i. 7.8 to 22) higher absolute risk of major low anterior resection syndrome, whereas survivors with T2D following right-sided and sigmoid resection had an 8 per cent higher risk of constipation (P < 0.001) but otherwise nearly the same long-term risk of bowel symptoms as those without T2D. For all types of colorectal cancer resections, T2D was associated with a 6–10 per cent higher risk of severe pain (P < 0.035) and a 4–8 per cent higher risk of impaired QoL. CONCLUSION: T2D at time of surgery was associated with a higher risk of long-term bowel dysfunction after rectal resection, but not after colon resection excluding a higher risk of constipation. T2D was associated with a slightly higher frequency of severe pain and inferior QoL after both rectal and colonic cancer resection

Age-associated Impairment of the Mucus Barrier Function is Associated with Profound Changes in Microbiota and Immunity

Aging significantly increases the vulnerability to gastrointestinal (GI) disorders but there are few studies investigating the key factors in aging that affect the GI tract. To address this knowledge gap, we used 10-week- and 19-month-old litter-mate mice to investigate microbiota and host gene expression changes in association with ageing. In aged mice the thickness of the colonic mucus layer was reduced about 6-fold relative to young mice, and more easily penetrable by luminal bacteria. This was linked to increased apoptosis of goblet cells in the upper part of the crypts. The barrier function of the small intestinal mucus was also compromised and the microbiota were frequently observed in contact with the villus epithelium. Antimicrobial Paneth cell factors Ang4 and lysozyme were expressed in significantly reduced amounts. These barrier defects were accompanied by major changes in the faecal microbiota and significantly decreased abundance of Akkermansia muciniphila which is strongly and negatively affected by old age in humans. Transcriptomics revealed age-associated decreases in the expression of immunity and other genes in intestinal mucosal tissue, including decreased T cell-specific transcripts and T cell signalling pathways. The physiological and immunological changes we observed in the intestine in old age, could have major consequences beyond the gut.</p