Myota GmbH

Understanding inflammatory responses after food consumption and at fasting is crucial for assessing the impact of diet on long-term health. To study these responses meaningfully, biomarkers must be responsive to food intake, consistent across individuals, and predictive of future health outcomes. Preliminary data suggest that anti-inflammatory short-chain fatty acids (SCFAs), produced by the microbiota from prebiotic fibre, might be relevant biomarkers in the food-induced inflammatory reaction, but data on their timing, magnitude, dynamics at fasting and during the postprandial state, and relationship with other biomarkers are currently lacking. This knowledge gap impacts our ability to identify reliable biomarkers that can be used as surrogate outcomes in dietary interventions and research focused on reducing chronic disease risk. In this biomarker discovery study, we aimed to identify meal-responsive inflammatory biomarkers and assess plasma SCFAs pharmacokinetics following meal intake. Three healthy male participants consumed three isoenergetic meals with different theoretical pro-inflammatory potential, one per week over a three-week period: an anti-inflammatory meal (Meal A), a pro-inflammatory meal (Meal B), and a pro-inflammatory meal with a butyrate-promoting prebiotic fibre supplement (Meal C). For each meal condition, blood samples were taken continually over a 30-h period, and inflammatory cytokines and plasma SCFAs were measured. Cytokine biomarker dynamics were classified based on their response to meals. We identified 26 meal-responsive biomarkers, with three-CST5, FGF-19, and ST1A1-showing consistent postprandial changes across participants. The study also revealed significant interindividual variability, with 23 biomarkers displaying highly personalised responses to food intake. Quantitative analysis of plasma SCFA concentrations indicated non-trivial dynamics, but a clear accumulation of butyrate, acetate, and propionate in plasma during a 25-h period following meal intake. Our findings highlight the complexity of the postprandial response, emphasising the need for thoughtful consideration of study design, including the choice and sampling rate of biomarkers. The identified biomarkers offer potential for future research and clinical applications, improving the understanding of diet-induced inflammation and its role in chronic disease prevention.

Prebiotic fibre represents a promising and efficacious treatment to manage pre-diabetes, acting via complementary pathways involving the gut microbiome and viscosity-related properties. In this study, we evaluated the effect of using a diverse prebiotic fibre supplement on glycaemic, lipid and inflammatory biomarkers in patients with pre-diabetes. Sixty-six patients diagnosed with pre-diabetes (yet not receiving glucose-lowering medications) were randomised into treatment (thirty-three) and placebo (thirty-three) interventions. Participants in the treatment arm consumed 20 g/d of a diverse prebiotic fibre supplement, and participants in the placebo arm consumed 2 g/d of cellulose for 24 weeks. A total of fifty-one and forty-eight participants completed the week 16 and week 24 visits, respectively. The intervention was well tolerated, with a high average adherence rate across groups. Our results extend upon previous work, showing a significant change in glycated haemoglobin (HbA1c) in the treatment group but only in participants with lower baseline HbA1c levels (< 6 % HbA1c) (P = 0·05; treatment –0·17 ± 0·27 v. placebo 0·07 ± 0·29, mean ± sd). Within the whole cohort, we showed significant improvements in insulin sensitivity (P = 0·03; treatment 1·62 ± 5·79 v. placebo –0·77 ± 2·11) and C-reactive protein (PFWE = 0·03; treatment –2·02 ± 6·42 v. placebo 0·94 ± 2·28) in the treatment group compared with the placebo. Together, our results support the use of a diverse prebiotic fibre supplement for physiologically relevant biomarkers in pre-diabetes.

Microbially derived short-chain fatty acids (SCFAs) in the human gut are tightly coupled to host metabolism, immune regulation and integrity of the intestinal epithelium. However, the production of SCFAs can vary widely between individuals consuming the same diet, with lower levels often associated with disease. A systems-scale mechanistic understanding of this heterogeneity is lacking. Here we use a microbial community-scale metabolic modelling (MCMM) approach to predict individual-specific SCFA production profiles to assess the impact of different dietary, prebiotic and probiotic inputs. We evaluate the quantitative accuracy of our MCMMs using in vitro and ex vivo data, plus published human cohort data. We find that MCMM SCFA predictions are significantly associated with blood-derived clinical chemistries, including cardiometabolic and immunological health markers, across a large human cohort. Finally, we demonstrate how MCMMs can be leveraged to design personalized dietary, prebiotic and probiotic interventions aimed at optimizing SCFA production in the gut. Our model represents an approach to direct gut microbiome engineering for precision health and nutrition.