Rates of colon cancer are much higher in African Americans (65:100,000) than in rural South Africans (<5:100,000). The higher rates are associated with higher animal protein and fat and lower fiber consumption, higher colonic secondary bile acids, lower colonic short chain fatty acid quantities and higher mucosal proliferative biomarkers of cancer risk in otherwise healthy middle aged volunteers. Here we investigate further the role of fat and fiber in this association. We performed two-week food exchanges in subjects from the same populations, where African Americans were fed a high-fiber, lowfat African-style diet, and rural Africans a high-fat low-fiber western-style diet under close supervision. In comparison to their usual diets, the food changes resulted in remarkable reciprocal changes in mucosal biomarkers of cancer risk and in aspects of the microbiota and metabolome known to affect cancer risk, best illustrated by increased saccharolytic fermentation and butyrogenesis and suppressed secondary bile acid synthesis in the African Americans.

ObjectiveTo highlight the contribution of the gut microbiota to the modulation of host metabolism by dietary inulin-type fructans (ITF prebiotics) in obese women.MethodsA double blind, placebo controlled, intervention study was performed with 30 obese women treated with ITF prebiotics (inulin/oligofructose 50/50 mix; n=15) or placebo (maltodextrin; n=15) for 3 months (16 g/day). Blood, faeces and urine sampling, oral glucose tolerance test, homeostasis model assessment and impedancemetry were performed before and after treatment. The gut microbial composition in faeces was analysed by phylogenetic microarray and qPCR analysis of 16S rDNA. Plasma and urine metabolic profiles were analysed by 1H-NMR spectroscopy.ResultsTreatment with ITF prebiotics, but not the placebo, led to an increase in Bifidobacterium and Faecalibacterium prausnitzii; both bacteria negatively correlated with serum lipopolysaccharide levels. ITF prebiotics also decreased Bacteroides intestinalis, Bacteroides vulgatus and Propionibacterium, an effect associated with a slight decrease in fat mass and with plasma lactate and phosphatidylcholine levels. No clear treatment clustering could be detected for gut microbial analysis or plasma and urine metabolomic profile analyses. However, ITF prebiotics led to subtle changes in the gut microbiota that may importantly impact on several key metabolites implicated in obesity and/or diabetes.ConclusionsITF prebiotics selectively changed the gut microbiota composition in obese women, leading to modest changes in host metabolism, as suggested by the correlation between some bacterial species and metabolic endotoxaemia or metabolomic signatures.

WHAT'S KNOWN ON THIS SUBJECT: Colic affects many infants, with incidence rates of up to 25%. The pathogenesis is not well understood. Initial studies based on traditional culturing approaches and in infants .6 weeks of age point at abnormalities in intestinal microbiota. WHAT THIS STUDY ADDS: Infants with colic showed lower microbiota diversity and stability than did control infants in the first weeks of life. Colic/control differences in the abundance of certain bacteria were also found at age 2 weeks. These microbial signatures possibly explain the excessive crying. abstract OBJECTIVES: To provide a comprehensive analysis of the fecal micro-biota in infants with colic, as compared with control infants, during their first 100 days of life. METHODS: Microbial DNA of .200 samples from 12 infants with colic and 12 age-matched control infants was extracted and hybridized to a phylogenetic microarray. RESULTS: Microbiota diversity gradually increased after birth only in the control group; moreover, in the first weeks, the diversity of the colic group was significantly lower than that of the control group. The stability of the successive samples also appeared to be significantly lower in the infants with colic for the first weeks. Further analyses revealed which bacterial groups were responsible for colic-related differences in microbiota at age 1 or 2 weeks, the earliest ages with significant differences. Proteobacteria were significantly increased in infants with colic compared with control infants, with a relative abundance that was more than twofold. In contrast, bifidobacteria and lactobacilli were significantly reduced in infants with colic. Moreover, the colic phenotype correlated positively with specific groups of proteobacteria, including bacteria related to Escherichia, Klebsiella, Serratia, Vibrio, Yersinia, and Pseudomonas, but negatively with bacteria belonging to the Bacteroidetes and Firmicutes phyla, the latter of which includes some lactobacilli and canonical groups known to produce butyrate and lactate. CONCLUSIONS: The results indicate the presence of microbial signatures in the first weeks of life in infants who later develop colic. These microbial signatures may be used to understand the excessive crying. The results offer opportunities for early diagnostics as well as for developing specific therapies. Pediatrics 2013;131:e550-e558 AUTHORS:

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Humans harbor a very complex and diverse collection of microbes, mostly bacteria, in their intestines that are collectively called the intestinal microbiota. It is known that we cannot live without the microbiota but on the other hand, the microbiota is associated to a number of intestinal and systemic diseases, including colorectal cancer (CRC). Nevertheless, the mechanisms underlying the key roles of the microbiota in health and disease are largely unknown. Compared to human populations in the Western countries, native Africans have a very low incidence and mortality of sporadic colorectal cancer (CRC). In contrast, African Americans, who are genetically similar to Africans, have a very high rate of CRC compared to other ethnic groups in the USA. Therefore, we hypothesize that differences in CRC risk between these groups is that the differential diets consumed by both groups (high fat and protein diets by African Americans; high starch and fibers diets by native Africans) impact the microbiota which as a result contributes to the differential CRC risk development. To test this hypothesis, we compared and contrasted the microbiota between African Americans, urbanized Africans (who live in a more Western semi-urban environment) and rural Africans at baseline, followed by a longitudinal study focusing on healthy middle aged African and African Americans volunteers who were subjected to reciprocal diet exchange under strict controlled in-house conditions over two weeks. Fresh fecal samples were collected and frozen immediately at baseline, and before and after diet exchange. DNA was isolated from these samples and subsequently used for microbiota profiling using the Human Intestinal Tract Chip (HITChip), which is a 16S ribosomal RNA-based phylogenetic microarray covering over 1,000 of the currently known bacterial species from the human intestine. HITChip profiling demonstrated that the microbiota composition is significantly different between the three groups at baseline with Prevotella (average abundance 22%), Oscillospira (average abundance 16%) and Bacteroides (28%) as key genera in urbanized Africans, rural Africans and African Americans, respectively. Co-occurrence analysis of microbial groups demonstrated that despite the differences in composition, the microbiota connectivity was similar between urban and rural Africans with potential butyrate producing and fiber consuming groups co-occurring at high correlation (p&gt;0.8) in both groups. Remarkably, these groups did not show strong co-occurrences within African Americans. We speculate that these co-occurrences represent interacting bacterial groups that form the structural core Compared to differences at baseline, the microbiota compositional changes were subtle after the short dietary exchange with only ten and two bacterial groups changing significantly (p&lt;0.01) in Africans and African Americans, respectively. Remarkably, the co-occurrence between bacterial groups changed reciprocally upon the diet exchange with more highly correlated (p&gt;0.8) co-occurring groups after consumption of the traditional African diet. We speculate that the decrease of co-occurring groups in the Western diet is associated to a weaker microbiota structure, which is more vulnerable for pertubations. In conclusion, our study demonstrated that long-term dietary patterns are likely responsible for the microbiota compositional differences observed between Africans and Americans, but that a short term dietary exchange can modify microbiota composition and structure. The fact that the microbiota structure changes reciprocally upon diet exchange holds promise for the prevention of diet-microbiota induced CRC risk. Citation Format: Erwin G. Zoetendal, Leo Lahti, Sebastian Tims, Philippe G.B. Puylaert, Junhai Ou, Kishore Vipperla, Willem M. de Vos, Stephen J. O'Keefe. Can variations in the intestinal microbiota explain differences in colon cancer risk?. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr SS01-03. doi:10.1158/1538-7755.DISP13-SS01-03