The role of microbes in the etiology of T2DM and other comorbidities of obesity might be made clear by studies on patients undergoing RYGB, since glycemic control is reported to improve within days (17
). However, this approach is made difficult by the lack of stool samples immediately after surgery, when intestinal mobility is temporarily impaired. Studies at several months after RYGB (29
) do not reflect immediate (pre-weight loss) postoperative changes. Therefore, in the present study, we examined bacteria from the oral cavity within 2 weeks of surgery when the most important changes are likely to have occurred.
Before RYGB, the subjects with T2DM had slightly higher levels of circulating endotoxin and TNF-α, and significantly higher levels of CRP (), consistent with previous reports (15
). At 2 weeks post-RYGB, levels of circulating endotoxin and TNF-α had fallen in subjects with T2DM (). This rapid decline in levels of endotoxin and TNF-α may be related to the changes in the microbiome and thus to the resolution of the hyperglycemia. However, it cannot be excluded that dietary changes were an important factor. The observed changes are not consistent with the notion that an elevated level of TNF-α is due solely to the presence of adipose tissue since the subjects were still morbidly obese. The small increase in the circulating level of CRP after surgery could be a consequence of the surgical procedure itself.
After RYGB, an improvement in glycemic control was seen in subjects with T2DM, with most patients being able to discontinue their hypoglycemic medication. This was expected and is consistent with previous reports (17
). The levels of Bifidobacteria
in stool samples were lower in patients with T2DM prior to surgery, consistent with other reports (14
Since the clinical and laboratory features of the participants conformed to what might be expected from the previously published literature, the study population does make a suitable group for the study of obesity-related conditions, such as T2DM and periodontal disease. On the contrary, it must be noted that patients undergoing RYGB are not a representative cross section of the global population of obese persons. The availability of RYGB is limited to individuals who meet specific criteria of motivation, compliance and resources. All of the subjects were drawn from the same geographical area, and the sample size was small. Possibly as a result of this selection process, no patient had periodontal disease despite the well-established association of periodontal disease with obesity (2
). Therefore, it might be difficult to study the progress of periodontal disease in this group.
The use of oral rinses to evaluate the GI tract microflora was found to be feasible. The major organisms of interest were readily detected in the oral rinses, and changes and differences were consistent with expectations. Bifidobacteria in the mouth were somewhat less in the subjects with T2DM who had HbA1c > 6.5% () and the concentration increased 10-fold within 2 weeks of surgery (). Such large differences were not observed for the other organisms examined. The levels of Bifidobacteria in the mouth appeared to reflect those in the lower GI tract, suggesting that a study of oral organisms could provide data with systemic implications. Although the magnitude of the postsurgical change did not achieve the 0.05 level of significance, a power analysis showed that this could feasibly be tested with a larger sample.
Simultaneous changes in oral and lower GI microbes could be due to the surgical procedure correcting a systemic mucosal immune defect as we previously proposed (19
). This could allow selected bacterial species to return to normal levels. Alternatively, the oral microflora could directly influence the postgastric microbiota, given that approximately 1 g of bacteria are swallowed per day (34
Two mechanisms have been proposed to explain the beneficial effects of Bifidobacteria
and related bacilli in T2DM (8
). The first is that they compete with pathogenic organisms, displacing them from the normal microflora (35
). If this is the case, then a microbiome-wide study of the oral organisms should identify organisms that are displaced. The second mechanism is that Bifidobacteria
binds endotoxin to their surface, preventing it from being transported across the mucosal barrier and into the circulation. Although some strains of Bifidobacteria
are extremely efficient at this, others are not (36
). Future studies of the oral microbiome should be aimed at examining variants of Bifidobacteria
or related organisms and explore possible associations with improvements in glycemic control. Any role for Bifidobacteria
or related organisms in protection from T2DM or other comorbidities of obesity has obvious implications for contributing to the prevention and treatment of the conditions.