Journal of IiMER as Clostridium difficile infection, inflammatory bowel disease and necrotizing enterocolitis. The sequence data can also be analyzed for differences in the abundance of various species between cases and controls. Some species that we found to be differentially abundant represented a very small fraction of the bacteria present and thus may not have a large effect on gut ecology and function. In Figure 3, we show those genera that a) represent more than 1% of the gut microbiome and 2) varied significantly among faecal samples between ME and healthy controls. The reduced abundances of Bifidobacterium and Faecalibacterium species in patients have also been reported in inflammatory bowel disease and other conditions. Faecalibacterium species produce butyrate, a short-chain fatty acid that has antiinflammatory properties, and thus its reduction would predict lower levels of butyrate. While we did not measure butyrate in our samples, when faecal samples of 34 female cases and 25 controls were examined by Armstrong et al. in another study, surprisingly, butyrate was higher in the ME patient samples. Determining which metabolites are actually present in the gut can be difficult to predict merely from a list of species that reside there, given the complex interactions among different microbial communities and with the cells in the intestine. Several studies in which bacteria were cultured also demonstrated differences between ME patients and controls. However, many gut microbial residents cannot be cultured and are known only by their DNA sequences, so that high-throughput sequencing of 16S ribosomal DNA for identifying bacterial taxonomic groups is beginning to supplant culture methods. Nevertheless, there are also limitations to knowledge from DNA sequences of intestinal contents. For example, while ribosomal DNA sequencing can detect that Escherichia coli is present, it doesn’t reveal whether one of the highly virulent E. coli strains is present in addition to benign or beneficial E. coli strains that reside in www.investinme.org most individuals. To find pathogenic E. coli, bacteria are grown on specific culture media and then tested with an antibody that reacts with proteins present in disease-causing E. coli strains. Thus, a harmful bacterium could be present in ME patients and go undetected by ribosomal DNA sequencing. Leaky gut problems When the intestinal lining is inflamed, bacteria can translocate into the bloodstream through loosened intestinal tight junctions leading to a ‘leaky gut’ (Figure 4). The immune system then detects the presence of bacteria or bacterial components in the blood and mounts an immune response to counter this apparent invasion. There can be collateral damage from the immune system’s attack on perceived threats. ME patients often have symptoms of chronic inflammation such as muscle and joint pain and swollen lymph nodes. In order to find out whether ME patients might have more bacterial products in their blood than healthy people and could be responding to them, we tested whether the levels of certain molecules were different in the blood of the same ME patients and healthy controls whose faecal samples were sequenced. We found that patients had higher levels of lipopolysaccharides (LPS), a large molecule comprised of both lipid and sugar components. LPS are present on the outer membrane of some bacteria and cause a strong immune response. We found that levels of LPS, LPS-binding proteins and a receptor for LPSbinding protein (soluble CD14), which signals the presence of LPS to the immune system, are increased in ME patients. Thus, the abnormal gut microbiome in ME patients likely contributes to their chronic inflammation and ensuing symptoms. While digestion most often comes to mind when considering intestinal bacterial species, there is increasing evidence that the gut microbiome affects the risk of colorectal cancer, obesity and abnormal mental function. Metabolites and proteins from the gut enter the bloodstream in healthy as well as diseased individuals, and some can affect the central Page 28 of 82
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