Dietary-Induced Bacterial Metabolites Reduce Inflammation and Inflammation-Associated Cancer via Vitamin D Pathway.

Environmental factors, including westernised diets and alterations to the gut microbiota, are considered risk factors for inflammatory bowel diseases (IBD). The mechanisms underpinning diet-microbiota-host interactions are poorly understood in IBD. We present evidence that feeding a lard-based high-fat (HF) diet can protect mice from developing DSS-induced acute and chronic colitis and colitis-associated cancer (CAC) by significantly reducing tumour burden/incidence, immune cell infiltration, cytokine profile, and cell proliferation. We show that HF protection was associated with increased gut microbial diversity and a significant reduction in Proteobacteria and an increase in Firmicutes and Clostridium cluster XIVa abundance. Microbial functionality was modulated in terms of signalling fatty acids and bile acids (BA). Faecal secondary BAs were significantly induced to include moieties that can activate the vitamin D receptor (VDR), a nuclear receptor richly represented in the intestine and colon. Indeed, colonic VDR downstream target genes were upregulated in HF-fed mice and in combinatorial lipid-BAs-treated intestinal HT29 epithelial cells. Collectively, our data indicate that HF diet protects against colitis and CAC risk through gut microbiota and BA metabolites modulating vitamin D targeting pathways. Our data highlights the complex relationship between dietary fat-induced alterations of microbiota-host interactions in IBD/CAC pathophysiology.

Isotopic and microbotanical insights into Iron Age agricultural reliance in the Central African rainforest.

The emergence of agriculture in Central Africa has previously been associated with the migration of Bantu-speaking populations during an anthropogenic or climate-driven 'opening' of the rainforest. However, such models are based on assumptions of environmental requirements of key crops (e.g. Pennisetum glaucum) and direct insights into human dietary reliance remain absent. Here, we utilise stable isotope analysis (δ13C, δ15N, δ18O) of human and animal remains and charred food remains, as well as plant microparticles from dental calculus, to assess the importance of incoming crops in the Congo Basin. Our data, spanning the early Iron Age to recent history, reveals variation in the adoption of cereals, with a persistent focus on forest and freshwater resources in some areas. These data provide new dietary evidence and document the longevity of mosaic subsistence strategies in the region.

The Root-Ely Modified Test of Rectus Femoris Spasticity Has Reliability in Individuals with Cerebral Palsy.

BACKGROUND: Stiff-knee gait is a common gait deviation in individuals with cerebral palsy (CP) due to rectus femoris (RF) muscle spasticity. The Duncan-Ely test is a velocity-dependent measurement of spasticity that is recorded as positive or negative. At our institution, we use a modification of the Duncan-Ely test, a 5-point ordinal rating scale, which delineates where the catch occurs within the rapid arc of knee flexion. It has been named the Root-Ely test. QUESTIONS/PURPOSES: We sought to determine the intra- and inter-rater reliability of the Duncan-Ely and Root-Ely tests in pediatric patients with CP. METHODS: A convenience sample of 20 ambulatory subjects was recruited; mean age was 10.5 ± 4.5 years, and the Gross Motor Function Classification System (GMFCS) levels were I-III. Five clinicians measured each individual's RF spasticity using the Root-Ely protocol during a single visit. Simple κ statistics with 95% confidence intervals (CI) were utilized for intra-rater reliability and weighted κ statistics with 95% CI for inter-rater reliability. RESULTS: The Root-Ely scale intra-rater reliability was 0.77 to 0.90 and inter-rater reliability was 0.32 to 0.87. Inter-rater reliability was good to excellent among experienced clinicians and fair to moderate in new clinicians. CONCLUSION: The Root-Ely 5-point scale has acceptable intra- and inter-rater reliability in pediatric individuals with CP among experienced clinicians. The Root-Ely test allows experienced clinicians to reliably quantify severity of RF spasticity and may give orthopaedic surgeons a clinical tool to better predict ideal candidates for RF transfers in individuals with CP in order to improve stiff-knee gait.

Exercise and the microbiota.

Sedentary lifestyle is linked with poor health, most commonly obesity and associated disorders, the corollary being that exercise offers a preventive strategy. However, the scope of exercise biology extends well beyond energy expenditure and has emerged as a great 'polypill', which is safe, reliable and cost-effective not only in disease prevention but also treatment. Biological mechanisms by which exercise influences homeostasis are becoming clearer and involve multi-organ systemic adaptations. Most of the elements of a modern lifestyle influence the indigenous microbiota but few studies have explored the effect of increased physical activity. While dietary responses to exercise obscure the influence of exercise alone on gut microbiota, professional athletes operating at the extremes of performance provide informative data. We assessed the relationship between extreme levels of exercise, associated dietary habits and gut microbiota composition, and discuss potential mechanisms by which exercise may exert a direct or indirect influence on gut microbiota.

Antimicrobials: Strategies for targeting obesity and metabolic health?

Obesity is associated with a number of serious health consequences, including type 2 diabetes, cardiovascular disease and a variety of cancers among others and has been repeatedly shown to be associated with a higher risk of mortality. The relatively recent discovery that the composition and metabolic activity of the gut microbiota may affect the risk of developing obesity and related disorders has led to an explosion of interest in this distinct research field. A corollary of these findings would suggest that modulation of gut microbial populations can have beneficial effects with respect to controlling obesity. In this addendum, we summarize our recent data, showing that therapeutic manipulation of the microbiota using different antimicrobial strategies may be a useful approach for the management of obesity and metabolic conditions. In addition, we will explore some of the mechanisms that may contribute to microbiota-induced susceptibility to obesity and metabolic diseases.

Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity.

OBJECTIVE: The gut microbiota is an environmental regulator of fat storage and adiposity. Whether the microbiota represents a realistic therapeutic target for improving metabolic health is unclear. This study explored two antimicrobial strategies for their impact on metabolic abnormalities in murine diet-induced obesity: oral vancomycin and a bacteriocin-producing probiotic (Lactobacillus salivarius UCC118 Bac(+)). DESIGN: Male (7-week-old) C57BL/J6 mice (9-10/group) were fed a low-fat (lean) or a high-fat diet for 20 weeks with/without vancomycin by gavage at 2 mg/day, or with L. salivarius UCC118Bac(+) or the bacteriocin-negative derivative L. salivarius UCC118Bac(-) (each at a dose of 1×10(9) cfu/day by gavage). Compositional analysis of the microbiota was by 16S rDNA amplicon pyrosequencing. RESULTS: Analysis of the gut microbiota showed that vancomycin treatment led to significant reductions in the proportions of Firmicutes and Bacteroidetes and a dramatic increase in Proteobacteria, with no change in Actinobacteria. Vancomycin-treated high-fat-fed mice gained less weight over the intervention period despite similar caloric intake, and had lower fasting blood glucose, plasma TNFα and triglyceride levels compared with diet-induced obese controls. The bacteriocin-producing probiotic had no significant impact on the proportions of Firmicutes but resulted in a relative increase in Bacteroidetes and Proteobacteria and a decrease in Actinobacteria compared with the non-bacteriocin-producing control. No improvement in metabolic profiles was observed in probiotic-fed diet-induced obese mice. CONCLUSION: Both vancomycin and the bacteriocin-producing probiotic altered the gut microbiota in diet-induced obese mice, but in distinct ways. Only vancomycin treatment resulted in an improvement in the metabolic abnormalities associated with obesity thereby establishing that while the gut microbiota is a realistic therapeutic target, the specificity of the antimicrobial agent employed is critical.