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Background: Interactions between diet, stress and the gut microbiome are of interest as a means to modulate health and performance. Here, in vitro fermentation was used to explore the effects of a sudden change in diet, 21 days sole sustenance on the Meal, Ready-to-Eat (MRE) U.S. military combat ration, on inter-species competition and functional potential of the human gut microbiota. Human fecal samples collected before and after MRE intervention or consuming a habitual diet (HAB) were introduced to nutrient-rich media supplemented with starch for in vitro fermentation under ascending colon conditions. 16S rRNA amplicon and Whole Genome Sequencing (WGS) were used to measure community composition and functional potential. Specific statistical analyses were implemented to detect changes in relative abundance from taxa, genes and pathways.Results: Differential changes in relative abundance of five taxa, Dorea spp., Akkermansia muciniphila, Prevotella spp., Desulfovibrio spp., and Dialister spp., and four Carbohydrate-Active Enzymes, specifically GH13_14, over the 24 h fermentation were observed as a function of the diet intervention and correlated to specific taxa of interest. Conclusions: These findings suggest that consuming MRE for 21 days minimally effects changes in gut microbiota structure in response to carbohydrate, but may induce alterations in metabolic capacity. Additionally, these findings demonstrate the potential of starch as a candidate supplemental strategy to functionally modulate specific gut commensals during stress-induced states.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

IL28B polymorphisms strongly predict spontaneous and treatment-induced clearance of hepatitis C virus (HCV) infection. A recent study proposed a 32-base pair deletion in the CC-chemokine receptor 5 (CCR5) gene (CCR5-D32) interacting with the IL28B polymorphisms to influence spontaneous HCV clearance. The aim of this study was to clarify the role of CCR5-D32 in treatmentinduced clearance of chronic hepatitis C (CHC). A cross-sectional cohort of 813 Caucasian patients with CHC genotype 1 (365 responders and 448 non-responders) who had received standard of care dual therapy with interferon (IFN)-a and ribavirin (RBV) was genotyped for the CCR5-D32 and IL28B polymorphisms to examine their interaction with respect to treatment response. CCR5-D32 did not influence treatment-induced recovery to IFN-a/RBV in CHC, and did not improve prediction of sustained virological response in the context of the IL28B polymorphisms in a multivariate model. CCR5-D32 homozygotes were significantly more frequent in those with CHC than healthy controls in the European cohorts (2.9% vs 0.4%, Po0.0001), but not in Australians of European ancestry. In conclusion, CCR5-D32 does not influence treatment response in the context of IL28B polymorphisms. Although CCR5-D32 may affect viral clearance within closely controlled geographical and genetic environments, we found no effect in larger cohorts treated with dual therapy. Refereed/Peer-reviewed