Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders.

The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a "poor" diet or protection against disease with a "healthy" diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders.

Association between breast cancer and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) gene 1595C/T SNP in a Pakistani population.

AIM OF THE STUDY: TRAIL-mediated signalling has emerged as an extensively studied biological mechanism reported to differentially induce apoptosis in cancer cells. However, overwhelmingly increasing experimentally verified data is shedding light on resistance against TRAIL-induced apoptosis in cancer cells. Moreover, genetic and epigenetic mutations also exert effects on the functionality of TRAIL and its receptors. In this study we investigated the association between breast cancer and polymorphisms in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) in a Pakistani Population. MATERIAL AND METHODS: Genotyping for TRAIL gene 1595 C/T polymorphism was done for 363 breast cancer patients and 193 age- and sex-matched healthy controls. DNA was extracted using standard organic methods. PCR-RFLP analysis was done for C/T polymorphism at position 1595 in exon 5 of the TRAIL gene using site-specific primers and restriction enzyme. The results were statistically evaluated by SPSS14. RESULTS: In this study, CC homozygotes were 46.3% in patients and 49.7% in controls, p = 0.729 with OR value 0.8705 (95% CI: 0.6137-1.2348). CT was statistically insignificant, p = 0.837 with OR value 0.9242 (95% CI: 0.6494-1.3154). However, the minor allele or risk allele genotype TT had a higher percentage among breast cancer patients (12.1%) than in the control group (6.7%). Since there was a statistically insignificant difference (p = 0.212, OR value 1.9098 with 95% CI 1.0019 to 3.6406) of TT genotype between the two groups, the contrastingly higher percentage of TT genotype in breast cancer patients seems to be a risk factor for the disease. Moreover, the frequency of minor allele T was also found to be higher in the patients (0.329) than in the controls (0.285). CONCLUSIONS: The TRAIL gene 1595 C/T SNP has a contradictory role in cancer development in different populations. In our population group although the percentage of homozygous risk allele TT was higher in patients it was statistically non-significant. The raised T allele and TT genotype in patients may suggest its association with breast cancer in the Pakistani population.