Distortions in any one of the microbiota functions or signaling pathways could potentially contribute to a wide range of diseases, including cardiovascular diseases (IBD) (bile-acid-associated regulation of serum cholesterol levels, chronic inflammation), diabetes (carbohydrate uptake and glycemic control), inflammatory diseases including atopic diseases, inflammatory bowel disease (inappropriate immune stimulation) and neoplastic diseases (carcinogen activation, chronic inflammation related hyperproliferation). Eloquent studies suggesting microbiota associations with obesity have recently received significant publicity[21–25
] but other studies have refuted the existence of such an association[26
]. Undoubtedly, the gut microbiota can contribute to differences in energy gain from fiber fermentation. The resulting small amounts of additional energy, if absorbed by the host, can over time, contribute to weight gain, and signaling from gut bacteria might contribute to fat storage. However, from a public health perspective, we might want to avoid shifting the focus away from a more direct path to avoid obesity: balance energy intake and output.
Changes in gut microbiota composition by probiotic supplementation of infant diets have been shown to reduce atopic disease[2,27
]. Associations between the microbiota development in infants and health later in life have long been proposed[28,29
]. Utilizing microarray technology to monitor microbiota, Palmer et al[30
] recently reported changes in the microbiota composition in 14 infants during the first year of life, pointing to considerable temporal variation and distinct features in each infant.
IBD has been linked to microbiota composition in a variety of studies[3,7,31–36
], and successful interventions using a pre- and/or probiotic approach have been reported. In addition to reports of differences in microbiota composition analyzed in fecal samples, the kinds and amounts of mucosa-adherent bacteria also seem to differ between cases with IBD and healthy controls[7,37–39
Colorectal cancer (CRC) risk also has been proposed to be associated with microbiota composition through various mechanisms[4,40
]. Pre- and or probiotics have reduced carcinogenesis in some but not all animal studies[41,42
]. Dietary prevention of intestinal carcino-genesis in APCMin
mice (mice that develop large numbers of intestinal tumors due to mutation in the adenomatous polyposis coli gene) was associated with correlated differences in overall microbiota profiles as well as with the presence of specific bacterial signatures[20
]. Increases in the amounts of intraepithelial Escherichia coli
) in CRC patients have been suggested[43
Interest has recently also been directed towards establishing a potential association between microbiota composition and both type 1 as well as type 2 diabetes mellitus. Brugman et al[44
] showed that antibiotics affected type 1 diabetes mellitus incidence but, more importantly, that microbiota differed before the onset of disease in diabetes-prone rats that developed type 2 diabetes. Similar data have recently been reported in immune system-associated studies in non-obese diabetic (NOD)-mice[45
]. Antibiotic-induced microbiota changes have also been shown to affect type 2 diabetes, but systemic effects likely contributed to this observation[46
Current studies of associations between microbiota composition and disease suffer from a lack of understanding regarding the normal range of microbiota diversity on a population level. Furthermore, the presence of particular microbes or microbiota pattern has been studied almost exclusively in observational studies, in which differences in microbiota were evaluated between subjects suffering from the respective disease and normal controls. This study design does not allow us to distinguish if differences in microbiota composition are causing the disease or if they are simply a result of the changed gut environment in diseased subjects. Prospective studies evaluating microbiota composition in individuals before they develop disease will be required to attribute causality to potential associations between microbiota and disease. Because such microbiota studies would be expensive and time consuming, they should be designed as ancillary projects as part of larger cohort studies.