Browsing by Author "Seethaler, Benjamin"

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    Elucidating the role of the gut microbiota in the physiological effects of dietary fiber
    (2022-05-13) Deehan, Edward C.; Zhang, Zhengxiao; Riva, Alessandra; Armet, Anissa M.; Perez-Muñoz, Maria E.; Nguyen, Nguyen K.; Krysa, Jacqueline A.; Seethaler, Benjamin; Zhao, Yuan-Yuan; Cole, Janis; Li, Fuyong; Hausmann, Bela; Spittler, Andreas; Nazare, Julie-Anne; Delzenne, Nathalie M.; Curtis, Jonathan M.; Wismer, Wendy V.; Proctor, Spencer D.; Bakal, Jeffrey A.; Bischoff, Stephan C.; Knights, Dan; Field, Catherine J.; Berry, David; Prado, Carla M.; Walter, Jens
    Abstract Background Dietary fiber is an integral part of a healthy diet, but questions remain about the mechanisms that underlie effects and the causal contributions of the gut microbiota. Here, we performed a 6-week exploratory trial in adults with excess weight (BMI: 25–35 kg/m2) to compare the effects of a high-dose (females: 25 g/day; males: 35 g/day) supplement of fermentable corn bran arabinoxylan (AX; n = 15) with that of microbiota-non-accessible microcrystalline cellulose (MCC; n = 16). Obesity-related surrogate endpoints and biomarkers of host-microbiome interactions implicated in the pathophysiology of obesity (trimethylamine N-oxide, gut hormones, cytokines, and measures of intestinal barrier integrity) were assessed. We then determined whether clinical outcomes could be predicted by fecal microbiota features or mechanistic biomarkers. Results AX enhanced satiety after a meal and decreased homeostatic model assessment of insulin resistance (HOMA-IR), while MCC reduced tumor necrosis factor-α and fecal calprotectin. Machine learning models determined that effects on satiety could be predicted by fecal bacterial taxa that utilized AX, as identified by bioorthogonal non-canonical amino acid tagging. Reductions in HOMA-IR and calprotectin were associated with shifts in fecal bile acids, but correlations were negative, suggesting that the benefits of fiber may not be mediated by their effects on bile acid pools. Biomarkers of host-microbiome interactions often linked to bacterial metabolites derived from fiber fermentation (short-chain fatty acids) were not affected by AX supplementation when compared to non-accessible MCC. Conclusion This study demonstrates the efficacy of purified dietary fibers when used as supplements and suggests that satietogenic effects of AX may be linked to bacterial taxa that ferment the fiber or utilize breakdown products. Other effects are likely microbiome independent. The findings provide a basis for fiber-type specific therapeutic applications and their personalization. Trial registration Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract
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    Gut microbiota modulation with long-chain corn bran arabinoxylan in adults with overweight and obesity is linked to an individualized temporal increase in fecal propionate
    (2020-08-19) Nguyen, Nguyen K; Deehan, Edward C; Zhang, Zhengxiao; Jin, Mingliang; Baskota, Nami; Perez-Muñoz, Maria E; Cole, Janis; Tuncil, Yunus E; Seethaler, Benjamin; Wang, Ting; Laville, Martine; Delzenne, Nathalie M; Bischoff, Stephan C; Hamaker, Bruce R; Martínez, Inés; Knights, Dan; Bakal, Jeffrey A; Prado, Carla M; Walter, Jens
    Abstract Background Variability in the health effects of dietary fiber might arise from inter-individual differences in the gut microbiota’s ability to ferment these substrates into beneficial metabolites. Our understanding of what drives this individuality is vastly incomplete and will require an ecological perspective as microbiomes function as complex inter-connected communities. Here, we performed a parallel two-arm, exploratory randomized controlled trial in 31 adults with overweight and class-I obesity to characterize the effects of long-chain, complex arabinoxylan (n = 15) at high supplementation doses (female: 25 g/day; male: 35 g/day) on gut microbiota composition and short-chain fatty acid production as compared to microcrystalline cellulose (n = 16, non-fermentable control), and integrated the findings using an ecological framework. Results Arabinoxylan resulted in a global shift in fecal bacterial community composition, reduced α-diversity, and the promotion of specific taxa, including operational taxonomic units related to Bifidobacterium longum, Blautia obeum, and Prevotella copri. Arabinoxylan further increased fecal propionate concentrations (p = 0.012, Friedman’s test), an effect that showed two distinct groupings of temporal responses in participants. The two groups showed differences in compositional shifts of the microbiota (p ≤ 0.025, PERMANOVA), and multiple linear regression (MLR) analyses revealed that the propionate response was predictable through shifts and, to a lesser degree, baseline composition of the microbiota. Principal components (PCs) derived from community data were better predictors in MLR models as compared to single taxa, indicating that arabinoxylan fermentation is the result of multi-species interactions within microbiomes. Conclusion This study showed that long-chain arabinoxylan modulates both microbiota composition and the output of health-relevant SCFAs, providing information for a more targeted application of this fiber. Variation in propionate production was linked to both compositional shifts and baseline composition, with PCs derived from shifts of the global microbial community showing the strongest associations. These findings constitute a proof-of-concept for the merit of an ecological framework that considers features of the wider gut microbial community for the prediction of metabolic outcomes of dietary fiber fermentation. This provides a basis to personalize the use of dietary fiber in nutritional application and to stratify human populations by relevant gut microbiota features to account for the inconsistent health effects in human intervention studies. Trial registration Clinicaltrials.gov, NCT02322112 , registered on July 3, 2015. Video Abstract