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Sonnenburg, E.

Publications and source records attributed to Sonnenburg, E..

4 recordsLinked to original sources

Fermentation-Derived Metabolites Shape Host Biology to Attenuate Severity of Inflammatory and Metabolic Disease

Fermented foods are among the few dietary interventions shown to increase gut microbiome diversity and reduce systemic inflammation in healthy adults, yet the underlying mechanisms remain poorly defined. Metabolites produced during food fermentation, termed fermentation-derived metabolites (FDMs), represent a largely uncharacterized pool of bioactive compounds that may directly mediate the physiological effects of fermented food consumption. Here, we characterize the metabolite landscape of ten vegetable-based fermented foods using metabolomics, identifying conserved enrichment of aromatic and branched-chain amino acid derivatives across diverse substrates. Using sauerkraut as a chemically representative model system, we show that metabolite extracts from wild green sauerkraut (wGS-FDMs) remodel intestinal and systemic immune populations and shift gut microbiome composition in healthy mice. wGS-FDMs suppressed NF-{kappa}B activation and pro-inflammatory cytokine secretion in vitro and decreased colitis severity in vivo. In a chronic high-fat diet model, wGS-FDMs attenuated weight gain and improved glucose and insulin tolerance, consistent with stimulation of GLP-1 secretion in vitro. Collectively, these findings establish FDMs as biologically potent dietary components capable of simultaneously modulating immune, microbial, and metabolic homeostasis across multiple physiological systems, positioning metabolites from fermented foods as an important and underappreciated class of dietary effectors in the context of chronic disease.

microbiology↗

Impact of a 7-day homogeneous diet on interpersonal variation in human gut microbiomes and metabolomes

Metabolism of dietary compounds by the gut microbiota generates a vast array of microbiome-dependent metabolites (MDMs), which are highly variable between individuals. The uremic MDMs (uMDMs) phenylacetylglutamine (PAG), p-cresol sulfate (PCS) and indoxyl sulfate (IS) accumulate during renal failure and are associated with poor outcomes. Targeted dietary interventions may reduce toxic MDMs generation; however, it is unclear if interindividual differences in diet or gut microbiome dominantly contribute to MDM variance. Here we use a 7-day homogeneous average American diet to standardize dietary precursor availability in 21 healthy individuals. Notably, the coefficient of variation in three uMDMs of interest, PAG, PCS, and IS (primary outcome), did not significantly decrease. The majority of circulating MDMs maintained variation despite identical diets. These results highlight the highly personalized profile of MDMs and limited contribution of short-term dietary heterogeneity, suggesting that dietary modification may need to be paired with microbial therapies to control MDM profiles.

microbiology↗

Gut Microbiota-Targeted Diets Modulate Human Immune Status

Diet modulates the gut microbiome, and gut microbes, in turn, can impact the immune system. Here, we used two gut microbiota-targeted dietary interventions, plant-based fiber or fermented foods, to determine how each influences the human microbiome and immune system in healthy adults. Using a 17-week randomized, prospective study design combined with -omics measurements of microbiome and host, including extensive immune profiling, we found distinct effects of each diet. High-fiber consumers showed increased gut microbiome-encoded glycan-degrading CAZymes despite stable community diversity. Three distinct immunological trajectories in high fiber-consumers corresponded to baseline microbiota diversity. Alternatively, the high-fermented food diet steadily increased microbiota diversity and decreased inflammatory markers. The data highlight how coupling dietary interventions to deep and longitudinal immune and microbiome profiling can provide individualized and population-wide insight. Our results indicate that fermented foods may be valuable in countering the decreased microbiome diversity and increased inflammation pervasive in the industrialized society.

microbiology↗

Mucin-derived O-glycans supplemented to diet mitigate diverse microbiota perturbations

Microbiota-accessible carbohydrates (MACs) are powerful modulators of microbiota composition and function. These substrates are often derived from diet, such as complex polysaccharides from plants or human milk oligosaccharides (HMOs) during breastfeeding. Host-derived mucus glycans on gut-secreted mucin proteins may serve as a continuous endogenous source of MACs for resident microbes; here we investigate the potential role of purified, orally-administered mucus glycans in maintaining a healthy microbial community. In this study, we liberated and purified O-linked glycans from porcine gastric mucin and assessed their efficacy in shaping the recovery of a perturbed microbiota in a mouse model. We found that porcine mucin glycans (PMGs) and HMOs enrich for taxonomically similar resident microbes. We demonstrate that PMGs aid recovery of the microbiota after antibiotic treatment, suppress C. difficile abundance, delay the onset of diet-induced obesity, and increase relative abundance of resident Akkermansia muciniphila. In silico analysis revealed that genes associated with mucus utilization are abundant and diverse in prevalent gut commensals and rare in enteric pathogens, consistent with these glycan-degrading capabilities being selected for during host development and throughout evolution of the host-microbe relationship. Importantly, we identify mucus glycans as a novel class of prebiotic compounds that can be used to mitigate perturbations to the microbiota and provide benefits to host physiology.

microbiology↗