Persistent changes in liver methylation and microbiome composition following reversal of diet-induced non-alcoholic-fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease that is thought to be reversible by changing the diet. To examine the impact of dietary changes on progression and cure of NAFLD, we fed mice a high-fat diet (HFD) or high-fructose diet (HFrD) for 9 weeks, followed by an additional 9 weeks, where mice were given normal chow diet. As predicted, the diet-induced NAFLD elicited changes in glucose tolerance, serum cholesterol, and triglyceride levels in both diet groups. Moreover, the diet-induced NAFLD phenotype was reversed, as measured by the recovery of glucose intolerance and high cholesterol levels when mice were given normal chow diet. However, surprisingly, the elevated serum triglyceride levels persisted. Metagenomic analysis revealed dietary-induced changes of microbiome composition, some of which remained altered even after reversing the diet to normal chow, as illustrated by species of the Odoribacter genus. Genome-wide DNA methylation analysis revealed a "priming effect" through changes in DNA methylation in key liver genes. For example, the lipid-regulating gene Apoa4 remained hypomethylated in both groups even after introduction to normal chow diet. Our results support that dietary change, in part, reverses the NAFLD phenotype. However, some diet-induced effects remain, such as changes in microbiome composition, elevated serum triglyceride levels, and hypomethylation of key liver genes. While the results are correlative in nature, it is tempting to speculate that the dietary-induced changes in microbiome composition may in part contribute to the persistent epigenetic modifications in the liver.

Lysine-Dendrimer, a New Non-Aggressive Solution to Rebalance the Microbiota of Acne-Prone Skin.

Acne is a chronic inflammatory skin disease that affects the quality of life of patients. Several treatments exist for acne, but their effectiveness tends to decrease over time due to increasing resistance to treatment and associated side effects. To circumvent these issues, a new approach has emerged that involves combating the pathogen Cutibacterium acnes while maintaining the homeostasis of the skin microbiome. Recently, it was shown that the use of a G2 lysine dendrigraft (G2 dendrimer) could specifically decrease the C. acnes phylotype (IAI) involved in acne, compared to non-acne-causing C. acnes (phylotype II) bacteria. In the present study, we demonstrate that the efficacy of this technology is related to its 3D structure, which, in contrast to the linear form, significantly decreases the inflammation factor (IL-8) linked to acne. In addition, our in-vitro data confirm the specific activity of the G2 dendrimer: after treatment of bacterial cultures and biofilms, the G2 dendrimer affected neither non-acneic C. acnes nor commensal bacteria of the skin (Staphylococcus epidermidis, S. hominis, and Corynebacterium minutissimum). In parallel, comparative in-vitro and in-vivo studies with traditional over-the-counter molecules showed G2's effects on the survival of commensal bacteria and the reduction of acne outbreaks. Finally, metagenomic analysis of the cutaneous microbiota of volunteers who applied a finished cosmetic product containing the G2 dendrimer confirmed the ability of G2 to rebalance cutaneous acne microbiota dysbiosis while maintaining commensal bacteria. These results confirm the value of using this G2 dendrimer to gently prevent the appearance of acne vulgaris while respecting the cutaneous microbiota.