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Background: Interactions between the diet and intestinal microbiota play a role in health and disease, including obesity and related metabolic complications. There is great interest to use dietary means to manipulate the microbiota to promote health. Currently, the impact of dietary change on the microbiota and the host metabolism is poorly predictable and highly individual. We propose that the responsiveness of the gut microbiota may depend on its composition, and associate with metabolic changes in the host. Methodology: Our study involved three independent cohorts of obese adults (n = 78) from Belgium, Finland, and Britain, participating in different dietary interventions aiming to improve metabolic health. We used a phylogenetic microarray for comprehensive fecal microbiota analysis at baseline and after the intervention. Blood cholesterol, insulin and inflammation markers were analyzed as indicators of host response. The data were divided into four training set – test set pairs; each intervention acted both as a part of a training set and as an independent test set. We used linear models to predict the responsiveness of the microbiota and the host, and logistic regression to predict responder vs. non-responder status, or increase vs. decrease of the health parameters. Principal Findings: Our models, based on the abundance of several, mainly Firmicute species at baseline, predicted the responsiveness of the microbiota (AUC  =  0.77–1; predicted vs. observed correlation  =  0.67–0.88). Many of the predictive taxa showed a non-linear relationship with the responsiveness. The microbiota response associated with the change in serum cholesterol levels with an AUC of 0.96, highlighting the involvement of the intestinal microbiota in metabolic health. Conclusion: This proof-of-principle study introduces the first potential microbial biomarkers for dietary responsiveness in obese individuals with impaired metabolic health, and reveals the potential of microbiota signatures for personalized nutrition. [ABSTRACT FROM AUTHOR]

The gut microbiota has recently been proposed as a novel component in the regulation of host homeostasis and immunity. We have assessed for the first time the role of the gut microbiota in a mouse model of leukemia (transplantation of BaF3 cells containing ectopic expression of Bcr-Abl), characterized at the final stage by a loss of fat mass, muscle atrophy, anorexia and inflammation. The gut microbial 16S rDNA analysis, using PCR-Denaturating Gradient Gel Electrophoresis and quantitative PCR, reveals a dysbiosis and a selective modulation of Lactobacillus spp. (decrease of L. reuteri and L. johnsonii/gasseri in favor of L. murinus/animalis) in the BaF3 mice compared to the controls. The restoration of Lactobacillus species by oral supplementation with L. reuteri 100-23 and L. gasseri 311476 reduced the expression of atrophy markers (Atrogin-1, MuRF1, LC3, Cathepsin L) in the gastrocnemius and in the tibialis, a phenomenon correlated with a decrease of inflammatory cytokines (interleukin-6, monocyte chemoattractant protein-1, interleukin-4, granulocyte colony-stimulating factor, quantified by multiplex immuno-assay). These positive effects are strain- and/or species-specific since L. acidophilus NCFM supplementation does not impact on muscle atrophy markers and systemic inflammation. Altogether, these results suggest that the gut microbiota could constitute a novel therapeutic target in the management of leukemia-associated inflammation and related disorders in the muscle. [ABSTRACT FROM AUTHOR]

Patients with non-alcoholic fatty liver disease are characterised by a decreased n-3/n-6 polyunsaturated fatty acid (PUFA) ratio in hepatic phospholipids. The metabolic consequences of n-3 PUFA depletion in the liver are poorly understood. We have reproduced a drastic drop in n-3 PUFA among hepatic phospholipids by feeding C57Bl/6J mice for 3 months with an n- 3 PUFA depleted diet (DEF) versus a control diet (CT), which only differed in the PUFA content. DEF mice exhibited hepatic insulin resistance (assessed by euglycemic-hyperinsulinemic clamp) and steatosis that was associated with a decrease in fatty acid oxidation and occurred despite a higher capacity for triglyceride secretion. Microarray and qPCR analysis of the liver tissue revealed higher expression of all the enzymes involved in lipogenesis in DEF mice compared to CT mice, as well as increased expression and activation of sterol regulatory element binding protein-1c (SREBP-1c). Our data suggest that the activation of the liver X receptor pathway is involved in the overexpression of SREBP-1c, and this phenomenon cannot be attributed to insulin or to endoplasmic reticulum stress responses. In conclusion, n-3 PUFA depletion in liver phospholipids leads to activation of SREBP-1c and lipogenesis, which contributes to hepatic steatosis. [ABSTRACT FROM AUTHOR]