Wholegrain fermentation affects gut microbiota composition, phenolic acid metabolism and pancreatic beta cell function in a rodent model of type 2 diabetes

The intestinal microbiota plays an important role in host metabolism via production of dietary metabolites. Microbiota imbalances are linked to type 2 diabetes (T2D), but dietary modification of the microbiota may promote glycemic control. Using a rodent model of T2D and an in vitro gut model system, this study investigated whether differences in gut microbiota between control mice and mice fed a high-fat, high-fructose (HFHFr) diet influenced the production of phenolic acid metabolites following fermentation of wholegrain (WW) and control wheat (CW). In addition, the study assessed whether changes in metabolite profiles affected pancreatic beta cell function. Fecal samples from control or HFHFr-fed mice were fermented in vitro with 0.1% (w/v) WW or CW for 0, 6, and 24 h. Microbiota composition was determined by bacterial 16S rRNA sequencing and phenolic acid (PA) profiles by UPLC-MS/MS. Cell viability, apoptosis and insulin release from pancreatic MIN6 beta cells and primary mouse islets were assessed in response to fermentation supernatants and selected PAs. HFHFr mice exhibited an overall dysbiotic microbiota with an increase in abundance of proteobacterial taxa (particularly Oxalobacteraceae) and Lachnospiraceae, and a decrease in Lactobacillus. A trend toward restoration of diversity and compositional reorganization was observed following WW fermentation at 6 h, although after 24 h, the HFHFr microbiota was monodominated by Cupriavidus. In parallel, the PA profile was significantly altered in the HFHFr group compared to controls with decreased levels of 3-OH-benzoic acid, 4-OH-benzoic acid, isoferulic acid and ferulic acid at 6 h of WW fermentation. In pancreatic beta cells, exposure to pre-fermentation supernatants led to inhibition of insulin release, which was reversed over fermentation time. We conclude that HFHFr mice as a model of T2D are characterized by a dysbiotic microbiota, which is modulated by the in vitro fermentation of WW. The differences in microbiota composition have implications for PA profile dynamics and for the secretory capacity of pancreatic beta cells

Scaling up cervical cancer screening in the midst of human papillomavirus vaccination advocacy in Thailand

<p>Abstract</p> <p>Background</p> <p>Screening tests for cervical cancer are effective in reducing the disease burden. In Thailand, a Pap smear program has been implemented throughout the country for 40 years. In 2008 the Ministry of Public Health (MoPH) unexpectedly decided to scale up the coverage of free cervical cancer screening services, to meet an ambitious target. This study analyzes the processes and factors that drove this policy innovation in the area of cervical cancer control in Thailand.</p> <p>Methods</p> <p>In-depth interviews with key policy actors and review of relevant documents were conducted in 2009. Data analysis was guided by a framework, developed on public policy models and existing literature on scaling-up health care interventions.</p> <p>Results</p> <p>Between 2006 and 2008 international organizations and the vaccine industry advocated the introduction of Human Papillomavirus (HPV) vaccine for the primary prevention of cervical cancer. Meanwhile, a local study suggested that the vaccine was considerably less cost-effective than cervical cancer screening in the Thai context. Then, from August to December 2008, the MoPH carried out a campaign to expand the coverage of its cervical cancer screening program, targeting one million women. The study reveals that several factors were influential in focusing the attention of policymakers on strengthening the screening services. These included the high burden of cervical cancer in Thailand, the launch of the HPV vaccine onto the global and domestic markets, the country’s political instability, and the dissemination of scientific evidence regarding the appropriateness of different options for cervical cancer prevention. Influenced by the country’s political crisis, the MoPH’s campaign was devised in a very short time. In the view of the responsible health officials, the campaign was not successful and indeed, did not achieve its ambitious target.</p> <p>Conclusion</p> <p>The Thai case study suggests that the political crisis was a crucial factor that drew the attention of policymakers to the cervical cancer problem and led the government to adopt a policy of expanding coverage of screening services. At the same time, the instability in the political system impeded the scaling up process, as it constrained the formulation and implementation of the policy in the later phase.</p

Gut microbiota, wholegrain polyphenols and pancreatic beta cell function in type 2 diabetes

Aims: The intestinal microbiota plays an important role in host metabolism via production of dietary metabolites. Microbiota imbalances are linked to type 2 diabetes, but dietary modification of the microbiota may promote glycaemic control. This study investigated whether differences in gut microbiota between control and diabetic mice influence the production of polyphenolic metabolites from wheat wholegrain (WW). Second, the study assessed whether changes in metabolite profiles affect pancreatic beta cell function. Methods: Faecal samples (1% (v/v)) from control or high‐fat high‐fructose fed (HFHF) mice were fermented in vitro with 0.1% (w/v) WW for 0, 6 and 24 h. Polyphenolic profiles were determined by UHPLC‐MS/MS and microbiota composition by bacterial 16S rRNA sequencing and qPCR. MIN6 beta cell apoptosis was assessed by measurement of caspase activity and insulin release by radioimmunoassay. Results: Levels of WW polyphenols were decreased in fermentation samples from HFHF with time and HFHF showed an overall dysbiotic microbiome profile (p 0.05, n=3). Insulin secretion was inhibited at 0 h by control, but not HFHF supernatant, and this effect was partly reverted at 24 h (p < 0.05, n=5). Conclusion: Our results suggest that a dysbiotic HFHF microbiota profile affects the production of polyphenolic metabolites with potential implications for beta cell function