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Probiotics are derived from traditional fermented foods, from beneficial commensals or from the environment. They act through diverse mechanisms affecting the composition or function of the commensal microbiota and by altering host epithelial and immunological responses. Certain probiotic interventions have shown promise in selected clinical conditions where aberrant microbiota have been reported, such as atopic dermatitis, necrotising enterocolitis, pouchitis and possibly irritable bowel syndrome. However, no studies have been conducted that can causally link clinical improvements to probiotic-induced microbiota changes. Whether a disease-prone microbiota pattern can be remodelled to a more robust, resilient and disease-free state by probiotic administration remains a key unanswered question. Progress in this area will be facilitated by: optimising strain, dose and product formulations, including protective commensal species; matching these formulations with selectively responsive subpopulations; and identifying ways to manipulate diet to modify bacterial profiles and metabolism.

A Western-style diet (WD), defined by high-fat, low-calcium, and vitamin D content, is associated with increased risk of human colorectal cancer. Understanding molecular mechanisms altered by the WD is crucial to develop preventive and therapeutic strategies. Effects of a WD on the colonic transcriptome of C57BI/6J mice, a model for sporadic colon cancer, were studied at endpoints before tumors occur. To assess whether a WD induces inflammatory changes, expression profiles of a broad spectrum of inflammatory proteins were performed and numbers of lamina propria macrophages were determined with semiquantitative morphometry. Transcriptome changes were translated into molecular interaction network maps and pathways. Pathways related to oxidative stress response; lipid, glutathione, and xenobiotic metabolism; and the immune response were perturbed by the WD. Several nuclear factor-erythroid 2-related factor 2- and aryl hydrocarbon receptor-dependent genes, including those coding for enzymes involved in phase 1 and 2 drug metabolism and oxidative stress responses, were induced. Oxidative stress was demonstrated by measurements of endogenous colonic redox-sensitive compound concentrations. Perturbations in immune response-related pathways, expression of inflammatory proteins, and increased numbers of lamina propria macrophages showed that the WD significantly alters the local cotonic immune response. Collectively, these data suggest that consumption of a WD interferes with networks of related biological response pathways involving colonic lipid metabolism, oxidative stress, and the immune response. These new findings impact our understanding of links between consumption of WD and colon carcinogenesis, providing additional information for developing preventive means for decreasing colorectal cancer risk. J. Nutr. 139: 2072-2078, 2009. doi: 10.3945/jn.108.104125

Previous studies have shown that epithelial cell production rates are increased throughout the gastrointestinal tract in aging rats. We tested the hypothesis that alteration in cell death (apoptosis) might be involved. Fischer 344 rats aged 4-5 months and 24-25 months fed ad libitum (AL) or calorie restricted (CR) to 60% of the AL intake were studied. Epithelial cell apoptosis was determined by a terminal deoxyuridine nucleotidyl nick end labeling (TUNEL) technique validated in our laboratory, and the expression of four members of the Bcl-2 family was evaluated by Western blotting in the small intestine and colon. The apoptotic index was low in young and aging AL and young CR rats. However, CR in aging rats was associated with a significantly higher apoptotic index in the jejunum and colon. The expression of the Bcl-2 family of genes was unchanged. Enhanced apoptosis in CR may protect the gastrointestinal tract from accumulation of DNA-altered cells during the aging process.

Studies on the proliferative activity of cells of the stomach, small intestine and colon with regard to aging are reviewed. Researches have shown that the aging human and rodent stomach have increased proliferation and decreased responsiveness to injury which may be important in the development and impaired healing of gastroduodenal ulcers. Production of relatively undifferentiated villus epithelium is also associated with aging in the rat intestine. On the other hand, crypt hyperplasia, increased rate of proliferation and a broadened proliferative zone are found in the colon of aging rats. The effects of injury, starvation and refeeding are also studied.

A review of literature on aging-related changes in intestinal lipid digestion and absorption is presented. The studies show that overall, lipid digestion and absorption are well-preserved in aging. Limitations of the studies, such as greater adverse effects of illness and experimental stress on animals and humans used in the studies, are mentioned. Areas deserving further study include adaptation to stress, intestinal motility and lipoprotein assembly and transport.