Diet complexity and estrogen receptor ß status affect the composition of the murine intestinal microbiota.

Intestinal microbial dysbiosis contributes to the dysmetabolism of luminal factors, including steroid hormones (sterones) that affect the development of chronic gastrointestinal inflammation and the incidence of sterone-responsive cancers of the breast, prostate, and colon. Little is known, however, about the role of specific host sterone nucleoreceptors, including estrogen receptor ß (ERß), in microbiota maintenance. Herein, we test the hypothesis that ERß status affects microbiota composition and determine if such compositionally distinct microbiota respond differently to changes in diet complexity that favor Proteobacteria enrichment. To this end, conventionally raised female ERß(+/+) and ERß(-/-) C57BL/6J mice (mean age of 27 weeks) were initially reared on 8604, a complex diet containing estrogenic isoflavones, and then fed AIN-76, an isoflavone-free semisynthetic diet, for 2 weeks. 16S rRNA gene surveys revealed that the fecal microbiota of 8604-fed mice and AIN-76-fed mice differed, as expected. The relative diversity of Proteobacteria, especially the Alphaproteobacteria and Gammaproteobacteria, increased significantly following the transition to AIN-76. Distinct patterns for beneficial Lactobacillales were exclusive to and highly abundant among 8604-fed mice, whereas several Proteobacteria were exclusive to AIN-76-fed mice. Interestingly, representative orders of the phyla Proteobacteria, Bacteroidetes, and Firmicutes, including the Lactobacillales, also differed as a function of murine ERß status. Overall, these interactions suggest that sterone nucleoreceptor status and diet complexity may play important roles in microbiota maintenance. Furthermore, we envision that this model for gastrointestinal dysbiosis may be used to identify novel probiotics, prebiotics, nutritional strategies, and pharmaceuticals for the prevention and resolution of Proteobacteria-rich dysbiosis.

Implementing Smarter Lunchrooms Makeovers in New York state middle schools: an initial process evaluation.

BACKGROUND: This paper presents design and findings from the process evaluation of a randomized controlled trial (RCT) testing the effectiveness of Smarter Lunchrooms Movement (SLM) interventions to encourage consumption of either fruit, vegetables, or unflavored milk in middle school cafeterias (grades 6-8, typically children ages 10-14 years). Using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework adapted for environmental interventions, the process evaluation monitored fidelity to SLM protocol, determined barriers and facilitators influencing fidelity, and identified the training and support needs of implementers. METHODS: Under research team guidance, community partners (interventionists) assisted school food service staff (providers) with a six week implementation of protocol items in 13 public middle school cafeterias (two milk treatment, three vegetable treatment, four fruit treatment, and four control) in New York State during the 2013-2014 academic year. Process evaluation measures included semi-quantitative measures of implementation and maintenance (lunchroom audits) and qualitative data (environmental assessments and semi-structured interviews with school food service staff). Analyses identified challenges and opportunities for improving intervention delivery. RESULTS: Approximately 75 % of enrolled students participated in school lunch programs and thus were exposed to the SLM intervention. Findings indicated potential contamination by other nutrition-related activities in the lunchroom and larger school environment may have affected the intervention impact. Modest implementation fidelity scores were observed for intervention treatments. Providers reported treatments were acceptable and feasible, however interventionists confirmed motivation and perceived effectiveness varied among schools. Post-intervention audits revealed limited maintenance of intervention protocols. Strategies to enhance buy-in and communication among providers and increased interventionist support are recommended. CONCLUSIONS: RE-AIM was a valuable framework for this process evaluation. Results highlighted implementation barriers and facilitators, and findings will enhance interpretation of forthcoming outcome data. Results will inform future iterations of the SLM RCT and provide valuable insights for those designing environmental interventions in school cafeterias.

Disruption of inducible 6-phosphofructo-2-kinase impairs the suppressive effect of PPARγ activation on diet-induced intestine inflammatory response.

PFKFB3 is a target gene of peroxisome proliferator-activated receptor gamma (PPARγ) and encodes for inducible 6-phosphofructo-2-kinase (iPFK2). As a key regulatory enzyme that stimulates glycolysis, PFKFB3/iPFK2 links adipocyte metabolic and inflammatory responses. Additionally, PFKFB3/iPFK2 is involved in the effect of active PPARγ on suppressing overnutrition-induced adipose tissue inflammatory response, which accounts for the insulin-sensitizing and antidiabetic effects of PPARγ activation. Using PFKFB3/iPFK2-disrupted mice, the present study investigated the role of PFKFB3/iPFK2 in regulating overnutrition-associated intestine inflammatory response and in mediating the effects of PPARγ activation. In wild-type mice, intestine PFKFB3/iPFK2 was increased in response to high-fat diet (HFD) feeding compared with that in mice fed a low-fat diet. However, intestine PFKFB3/iPFK2 was decreased in PFKFB3/iPFK2-disrupted mice and did not respond to HFD feeding. Furthermore, on an HFD, PFKFB3/iPFK2-disrupted mice displayed a significant increase in major intestine proinflammatory indicators such as toll-like receptor 4 expression, c-Jun N-terminal kinase 1 and nuclear factor kappa B phosphorylation, and proinflammatory cytokine expression compared with wild-type littermates. Upon treatment with rosiglitazone, an agonist of PPARγ, intestine proinflammatory indicators were markedly decreased in wild-type mice, but to a much lesser degree in PFKFB3/iPFK2-disrupted mice. Overall, the status of HFD-induced intestine inflammatory response in all treated mice correlated inversely with systemic insulin sensitivity, indicated by the homeostasis model assessment of insulin resistance data. Together, these results suggest that PFKFB3/iPFK2 is critically involved in the effect of PPARγ activation on suppressing diet-induced intestine inflammatory response.