Ruminant milk and soy solids differentially affect growth, colon gene and protein expression, and microbiota profiles in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease

Nicole Roy, AgResearch Limited Grasslands Research Centre, Palmerston North, New Zealand

A.E. Russ1,2,3, M.P.G. Barnett1,3, W. Young1, J. Cooney3,4, R.C. Anderson1, W.C. McNabb1,3,4, N.C. Roy1,3,4
1. Food Nutrition & Health Team, AgResearch Grasslands, Palmerston North, New Zealand;
2. Institute of Food, Nutrition and Human Health, Massey University, Palmerston North, New Zealand;
3. Nutrigenomics New Zealand (www.nutrigenomics.org.nz);
4. Riddet Institute, Massey University, Palmerston North, New Zealand; Plant and Food Research, Hamilton, New Zealand

The term inflammatory bowel disease (IBD) refers to immune-mediated diseases characterized by chronic intestinal inflammation. Ruminant milks form an important part of the human diet, but people with IBD are often advised to avoid dairy products and may substitute them for soy products.

Milk and soy contain bioactive molecules with antibacterial, anti-inflammatory, and other immunomodulatory actions which may be of use in the prevention or treatment of IBD. The responses of people with IBD to milk may be influenced by their genotype, and by the composition and genotype of their intestinal microbiota. It is thus important to bear these factors in mind when investigating the effects of milk diets on the molecular pathways involved in the inflammatory process. A better understanding of these pathways may contribute to the use of milk components or different types of milk to prevent and/or reduce the inflammation associated with IBD.

The first aim of this study was to determine whether diets containing solids from different ruminant milks, or from soy, reduce intestinal inflammation in interleukin-10 gene-deficient (Il10–/–) mice, a model of human IBD. The second aim was to investigate changes in biochemical pathways and microbiota composition that may indicate mechanisms by which these diets altered the inflam-matory process.

Male Il10-/- mice (15 per treatment) and C57BL/6J (control) mice (9 per treatment) were fed diets containing 40% (w/w) sheep, goat, or cow whole milk powder, 40% (w/w) soy solids, or one of two control diets (casein-free modified-AIN-76A or standard AIN-76A) from 4 to 11 weeks of age. For all diets except AIN-76A, total protein, fat, carbohydrate and energy were as similar as possible. Body weight and food intake were measured three times weekly throughout the experiment, and intestinal tissue was taken at 11 weeks of age for histopathological evaluation of inflammation and transcriptomic/ proteomic analyses. Caecal contents were also collected to characterize intestinal microbiota composition.

Male Il10-/- mice (but not controls) fed the cow and goat milk diets ate less and gained less weight than all other diet groups. Il10-/- mice fed the cow and goat milk diets had reduced colon histological injury scores relative to those on the other diets. Final bodyweight, average intake per day, and colon histological injury scores of Il10-/- mice were not different from control diets for soy and sheep milk diets. Il10-/- mice on the cow and goat milk diets also had decreased expression levels of many immune/inflammatory-related genes and altered expression patterns in immune-related pathways, processes and gene sets. Changes in the levels of some colon tissue proteins were also associated with the reduction in colon inflammation. A strain-diet interaction was seen in the composition of caecal microbiota, where community profiles could be distinguished not only by mouse strain, but also by the type of milk the mice received; particularly cow and goat.

Diets incorporating solids from cow and goat milks affected the growth of Il10–/– mice and also influenced colon inflammation relative to control diets. Reduced levels of colon inflammation in Il10–/– mice fed cow and goat milk were associated with alterations in gene and protein expression and microbiota composition, suggesting the presence of milk components with anti-inflammatory effects. Interactions between the microbiota and biochemical pathways in the colon tissue in response to dietary intervention with different types of milk, and the possible role of these interactions in reducing inflammation, requires further investigation, as does the mechanism of growth reduction. This research may contribute to preventative or therapeutic nutritional interventions for people with IBD.

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