Microbial-derived short-chain fatty acids (SCFA) acetate, propionate and butyrate may provide a link between gut microbiota and whole-body insulin sensitivity (IS). In this cross-sectional study (160 participants, 64% male, BMI: 19.2–41.0 kg/m², normal or impaired glucose metabolism), associations between SCFA (faecal and fasting circulating) and circulating metabolites, substrate oxidation and IS were investigated. In a subgroup (n = 93), IS was determined using a hyperinsulinemic-euglycemic clamp. Data were analyzed using multiple linear regression analysis adjusted for sex, age and BMI. Fasting circulating acetate, propionate and butyrate concentrations were positively associated with fasting GLP-1 concentrations. Additionally, circulating SCFA were negatively related to whole-body lipolysis (glycerol), triacylglycerols and free fatty acids levels (standardized (std) β adjusted (adj) −0.190, P = 0.023; std β adj −0.202, P = 0.010; std β adj −0.306, P = 0.001, respectively). Circulating acetate and propionate were, respectively, negatively and positively correlated with IS (M-value: std β adj −0.294, P < 0.001; std β adj 0.161, P = 0.033, respectively). We show that circulating rather than faecal SCFA were associated with GLP-1 concentrations, whole-body lipolysis and peripheral IS in humans. Therefore, circulating SCFA are more directly linked to metabolic health, which indicates the need to measure circulating SCFA in human prebiotic/probiotic intervention studies as a biomarker/mediator of effects on host metabolism.

Longer colonic transit time and hard stools are associated with increased gut microbiota diversity. Here, we investigate to what extent quantitative measures of (segmental) colonic transit time were related to gut microbiota composition, microbial metabolites, and gut-related parameters in a human cross-sectional study. Using radiopaque markers, (segmental) colonic transit time (CTT) was measured in 48 lean/overweight participants with long colonic transit but without constipation. Fecal microbiota composition was determined using 16S rRNA gene amplicon sequencing. Associations between gastrointestinal transit (segmental CTT and stool frequency and consistency), microbiota diversity and composition, microbial metabolites [short-chain fatty acids (SCFA), branched-chain fatty acids, and breath hydrogen], habitual diet, and gut-related host parameters [lipopolysaccharide-binding protein (LBP) and fecal calprotectin] were investigated using univariate and multivariate approaches. Long descending (i.e., distal) colonic transit was associated with increased microbial α-diversity but not with stool consistency. Using unweighted and weighted UniFrac distance, microbiota variation was not related to (segmental) CTT but to demographics, diet, plasma LBP, and fecal calprotectin. Bray–Curtis dissimilarity related only to stool consistency. Rectosigmoid and descending colonic transit were negatively associated with fecal SCFA and plasma acetate, respectively. This study suggests that the distal colon transit may affect not only microbiota diversity but also microbial metabolism.NEW & NOTEWORTHY We extend previous findings showing that long distal colonic transit time influences microbial diversification and fermentation, whereas stool consistency is related to microbiota composition in humans with a long colonic transit. This study puts the importance of the (distal) colonic site in microbiota ecology forward, which should be considered in future therapeutic studies targeting, for instance, short-chain fatty acid production to improve metabolic health.

Acute intake of the wheat bran extract Arabinoxylan-Oligosaccharide (AXOS) modulates the gut microbiota, improves stool characteristics and postprandial glycemia in healthy humans. Yet, little is known on how long-term AXOS intake influences gastrointestinal (GI) functioning, gut microbiota, and metabolic health. In this randomized, placebo-controlled, double-blind study, we evaluated the effects of AXOS intake on GI function and metabolic health in adults with slow GI transit without constipation. Forty-eight normoglycemic adults were included with whole-gut transit time (WGTT) of >35 h receiving either 15 g/day AXOS or placebo (maltodextrin) for 12-wks. The primary outcome was WGTT, and secondary outcomes included stool parameters, gut permeability, short-chain fatty acids (SCFA), microbiota composition, energy expenditure, substrate oxidation, glucose, insulin, lipids, gut hormones, and adipose tissue (AT) function. WGTT was unchanged, but stool consistency softened after AXOS. 12-wks of AXOS intake significantly changed the microbiota by increasing Bifidobacterium and decreasing microbial alpha-diversity. With a good classification accuracy, overall microbiota composition classified responders with decreased WGTT after AXOS. The incretin hormone Glucagon-like protein 1 was reduced after AXOS compared to placebo. Energy expenditure, plasma metabolites, AT parameters, SCFA, and gut permeability were unchanged. In conclusion, intake of wheat bran extract increases fecal Bifidobacterium and softens stool consistency without major effects on energy metabolism in healthy humans with a slow GI transit. We show that overall gut microbiota classified responders with decreased WGTT after AXOS highlighting that GI transit and change thereof were associated with gut microbiota independent of Bifidobacterium. NCT02491125

The mucosal immune system is relevant for homeostasis, immunity, and also pathological conditions in the gastrointestinal tract. Inducible NO synthase (iNOS)–dependent production of NO is one of the factors linked to both antimicrobial immunity and pathological conditions. Upregulation of iNOS has been observed in human Helicobacter pylori infection, but the cellular sources of iNOS are ill defined. Key differences in regulation of iNOS expression impair the translation from mouse models to human medicine. To characterize mucosal iNOS-producing leukocytes, biopsy specimens from H. pylori–infected patients, controls, and participants of a vaccination trial were analyzed by immunohistochemistry, along with flow cytometric analyses of lymphocytes for iNOS expression and activity. We newly identified mucosal IgA-producing plasma cells (PCs) as one major iNOS⁺ cell population in H. pylori–infected patients and confirmed intracellular NO production. Because we did not detect iNOS⁺ PCs in three distinct infectious diseases, this is not a general feature of mucosal PCs under conditions of infection. Furthermore, numbers of mucosal iNOS⁺ PCs were elevated in individuals who had cleared experimental H. pylori infection compared with those who had not. Thus, IgA⁺ PCs expressing iNOS are described for the first time, to our knowledge, in humans. iNOS⁺ PCs are induced in the course of human H. pylori infection, and their abundance seems to correlate with the clinical course of the infection.

Interest in plant-based nutrition has steadily increased in the western world in the recent years. The number of people following a meat-reduced, flexitarian diet is growing continuously. However, little is known about the diet quality of flexitarians compared to vegans or omnivores. Therefore, in this cross-sectional study, the food intake of 94 participants aged between 25–45 years was recorded via a validated food frequency questionnaire and 28 self-designed questions about the consumption of plant-based alternatives. An adapted Healthy Eating Index, HEI-flex, was developed to evaluate the diet quality of flexitarians, vegans and omnivores. Higher score points (SP) of the HEI-flex are associated with higher compliance with the official diet recommendations (V_max = 100 SP). Finally, flexitarians scored significantly more highly when compared to omnivores (54 ± 8 vs. 47 ± 9 SP; p = 0.008) but lower than vegans (54 ± 8 vs. 61 ± 10 SP; p = 0.010). The results showed that the HEI-flex is a useful tool for assessing and comparing the diet quality of flexitarians, vegans and omnivores. Despite the consumption of highly processed plant-based alternatives, reduction in meat and meat products seems to be accompanied by increased overall diet quality.

The intermediate state between normal glucose tolerance and overt type 2 diabetes mellitus is associated with micro- and macrovascular diseases, requiring safe and cost-effective treatment measures interventions. A novel source of LC n-3 FAs is Calanus finmarchicus Oil, which showed promising effects on glucose homeostasis in preclinical studies due to anti-obesity effects and/or anti-inflammatory properties. In total, 43 obese patients (BMI: 31.7 ± 5.2 kg/m²) were allocated in the following two groups: (1) Calanus oil group (2 g CO/day) and (2) placebo group (2 g paraffin oil/day). Markers of glucose metabolism, body composition and energy intake were measured at the beginning (t0), after 12 weeks (t₁₂) and 16 weeks (t₁₆). Overall, parameters reflecting abnormal glucose homeostasis and insulin resistance in the liver, including fasting insulin (−2.9 mU/L ± 4.10, p < 0.05), HOMA-IR (−0.9 ± 1.28, p < 0.05) and hepatic insulin resistance index (−1.06 ± 1.72 × 10⁶, p < 0.05) significantly enhanced after a 12-week CO-intervention, while no differences were observed in HbA1c, AUC_0–2h Glucose, AUC_0–2h Insulin, 2 h plasma glucose and muscle insulin sensitivity index. Our results indicate that Calanus oil causes beneficial effects on glucose metabolism and insulin resistance in obese patients, with clinical relevance to be verified in further studies. In addition, the possible active compounds and their mechanisms of action should be elucidated.