Human milk oligosaccharides induce acute yet reversible compositional changes in the gut microbiota of conventional mice linked to a reduction of butyrate levels.

Human Milk Oligosaccharides (HMOs) are glycans with prebiotic properties known to drive microbial selection in the infant gut, which in turn influences immune development and future health. Bifidobacteria are specialized in HMO degradation and frequently dominate the gut microbiota of breastfed infants. However, some species of Bacteroidaceae also degrade HMOs, which may prompt selection also of these species in the gut microbiota. To investigate to what extent specific HMOs affect the abundance of naturally occurring Bacteroidaceae species in a complex mammalian gut environment, we conducted a study in 40 female NMRI mice administered three structurally different HMOs, namely 6'sialyllactose (6'SL, n = 8), 3-fucosyllactose (3FL, n = 16), and Lacto-N-Tetraose (LNT, n = 8), through drinking water (5%). Compared to a control group receiving unsupplemented drinking water (n = 8), supplementation with each of the HMOs significantly increased both the absolute and relative abundance of Bacteroidaceae species in faecal samples and affected the overall microbial composition analyzed by 16s rRNA amplicon sequencing. The compositional differences were mainly attributed to an increase in the relative abundance of the genus Phocaeicola (formerly Bacteroides) and a concomitant decrease of the genus Lacrimispora (formerly Clostridium XIVa cluster). During a 1-week washout period performed specifically for the 3FL group, this effect was reversed. Short-chain fatty acid analysis of faecal water revealed a decrease in acetate, butyrate and isobutyrate levels in animals supplemented with 3FL, which may reflect the observed decrease in the Lacrimispora genus. This study highlights HMO-driven Bacteroidaceae selection in the gut environment, which may cause a reduction of butyrate-producing clostridia.

Elevated Glucagon-like Peptide-1 and a Th2 Shift May Support Reduced Prevalence of Thoracic Aortic Aneurysm in Patients with Diabetes.

Glucagon-like peptide-1 (GLP-1) regulates processes involved in the pathophysiology of thoracic aortic aneurysms (TAAs), including inflammation, while protecting against aortic aneurysms in animal models. Type 2 diabetes (T2D) involves altered GLP-1 signaling due to pathology and/or therapy and is associated with reduced prevalence of TAAs. We aimed to assess whether T2D alters the inflammatory profile/proteolytic activity, possible correlations to elevated fasting GLP-1 (F-GLP-1), and its relevance for TAA. F-GLP-1, pro-inflammatory T helper 1 (Th1) cytokines, Th2 cytokines, C-reactive protein, and matrix metalloproteinase-2 activity (MMP-2) were analyzed in surgical patients with aortic valve pathology with/without T2D and without T2D but with TAA. Patients with T2D displayed an increase in the relative systemic expression of interleukin 6 and tumor necrosis factor α and a clear trend towards reduced levels of interferon γ (IFNγ). In addition, a positive association between GLP-1 and the plasma interleukin 4 (IL-4)/IFNγ ratio was detected. TAA was associated with significantly lower plasma levels of the Th2 cytokines IL-4 and interleukin 5. Plasma MMP-2 activity did not differ between groups. We conclude that T2D involved a Th2 shift, which associates with elevated F-GLP-1 and may-considering Th1 bias in TAA-contribute to reduced prevalence of TAA in T2D.