Bridging the Gap from Enterotypes to Personalized Dietary Recommendations: A Metabolomics Perspective on Microbiome Research

Advances in high-throughput DNA sequencing have propelled research into the human microbiome and its link to metabolic health. We explore microbiome analysis methods, specifically emphasizing metabolomics, how dietary choices impact the production of microbial metabolites, providing an overview of studies examining the connection between enterotypes and diet, and thus, improvement of personalized dietary recommendations. Acetate, propionate, and butyrate constitute more than 95% of the collective pool of short-chain fatty acids. Conflicting data on acetate’s effects may result from its dynamic signaling, which can vary depending on physiological conditions and metabolic phenotypes. Human studies suggest that propionate has overall anti-obesity effects due to its well-documented chemistry, cellular signaling mechanisms, and various clinical benefits. Butyrate, similar to propionate, has the ability to reduce obesity by stimulating the release of appetite-suppressing hormones and promoting the synthesis of leptin. Tryptophan affects systemic hormone secretion, with indole stimulating the release of GLP-1, which impacts insulin secretion, appetite suppression, and gastric emptying. Bile acids, synthesized from cholesterol in the liver and subsequently modified by gut bacteria, play an essential role in the digestion and absorption of dietary fats and fat-soluble vitamins, but they also interact directly with intestinal microbiota and their metabolites. One study using statistical methods identified primarily two groupings of enterotypes Bacteroides and Ruminococcus. The Prevotella-dominated enterotype, P-type, in humans correlates with vegetarians, high-fiber and carbohydrate-rich diets, and traditional diets. Conversely, individuals who consume diets rich in animal fats and proteins, typical in Western-style diets, often exhibit the Bacteroides-dominated, B-type, enterotype. The P-type showcases efficient hydrolytic enzymes for plant fiber degradation but has limited lipid and protein fermentation capacity. Conversely, the B-type features specialized enzymes tailored for the degradation of animal-derived carbohydrates and proteins, showcasing an enhanced saccharolytic and proteolytic potential. Generally, models excel at predictions but often struggle to fully elucidate why certain substances yield varied responses. These studies provide valuable insights into the potential for personalized dietary recommendations based on enterotype

Associations between the Dietary Inflammatory Index, the Gut Microbiome, and Nutritional Status in Elderly Individuals (Abstract)

Diet can influence healthy aging through anti- or proinflammatory effects, partly by modulating the gut microbiome composition. This study investigated the relationships between the Dietary Inflammatory Index (DII), the gut microbiome, and nutritional status in elderly individuals. Methods: This cross-sectional analysis included 114 home-dwelling individuals aged over 70 years. The Energy-adjusted DII (E-DII) was calculated from 3-day food diaries, and blood samples were taken to measure micronutrient status, glucose, and lipid metabolism. Body composition was assessed using bioimpedance, and fecal gut microbiome composition was analyzed through 16S rRNA gene sequencing. The participants were categorized into maintaining an anti-inflammatory diet (AD) and a pro-inflammatory diet (PD) based on the median E-DII score. The associations of E-DII groups with blood markers and microbial diversity and composition were examined using the analysis of covariance, permutational analysis of variance, and multivariate linear models. Results: The AD (n = 57, 76 ± 3.83 years) and PD (n = 57, 75 ± 5.21 years) groups were similar in age but differed in sex distribution, with a higher proportion of females in the AD group (p = 0.02). When compared to the PD group and adjusted for sex, the AD group had a lower body mass index, fat mass, fasting insulin level, HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), fasting triglycerides, and serum uric acid concentration (all p < 0.05), with higher concentrations of high-density lipoprotein, red-blood-cell folate (RBC), and Omega-3 index (all p < 0.05). While the microbial diversity and composition did not differ between the DII groups, folate concentrations were negatively associated with Agathobacter and positively associated with Bacteroides abundance (both q = 0.23). Lower uric acid concentrations were associated with a higher abundance of Bifidobacterium (q = 0.09) and lower abundance of Phocaeicola (q = 0.11). Discussion: The study suggests that following an anti-inflammatory diet is associated with improved nutritional status in the elderly. Dietary blood markers, rather than E-DII, were found to be associated with the gut microbiome, suggesting a potential link between the microbiome and changes in nutritional markers independent of diet. Further studies are needed to explore the causal relationship between dietary inflammatory potential, gut microbiome, and healthy aging

ADAM8 expression in invasive breast cancer promotes tumor dissemination and metastasis

International audienceThe transmembrane metalloprotease-disintegrin ADAM8 mediates cell adhesion and shedding of ligands, receptors and extracellular matrix components. Here, we report that ADAM8 is abundantly expressed in breast tumors and derived metastases compared to normal tissue, especially in triple-negative breast cancers (TNBCs). Furthermore, high ADAM8 levels predicted poor patient outcome. Consistently, ADAM8 promoted an aggressive phenotype of TNBC cells in culture. In a mouse orthotopic model, tumors derived from TNBC cells with ADAM8 knockdown failed to grow beyond a palpable size and displayed poor vascularization. Circulating tumor cells and brain metastases were also significantly reduced. Mechanisti-cally, ADAM8 stimulated both angiogenesis through release of VEGF-A and transendothelial cell migration via β1-integrin activation. In vivo, treatment with an anti-ADAM8 antibody from the time of cell inoculation reduced primary tumor burden and metastases. Furthermore, antibody treatment of established tumors profoundly decreased metastases in a resection model. As a non-essential protein under physiological conditions, ADAM8 represents a promising novel target for treatment of TNBCs, which currently lack targeted therapies and frequently progress with fatal dissemination