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Dirks, B.

Publications and source records attributed to Dirks, B..

3 recordsLinked to original sources

Microbial Feast or Famine: dietary carbohydrate composition and gut microbiota metabolic function

Diet composition plays a major role in shaping the structure and function of the gut microbiota and influencing host health. While numerous studies have investigated the impact of macronutrient type and quantity on microbiota using in vitro systems, animal models, and human participants, most of these studies focused primarily on microbial-community composition and lacked the functional information that can be gained from transcript-level analyses. In this exploratory analysis, we use metatranscriptomic data to gain a functional perspective on how dietary composition is associated with the gut microbiota and hypothesized implications for host physiology. Data were derived from a tightly controlled, randomized cross-over feeding study conducted in a metabolic ward, where participants consumed two isocaloric and eucaloric diets differing in food processing and fiber content: A Western Diet (WD) limited in fiber, resistant starch, and whole foods and a Microbiome Enhancer Diet (MBD) composed of fiber-rich, whole foods. Our prior findings showed that a WD lead to a resource-limited microbiota enriched in mucin-degrading bacteria that resorted to metabolizing host-derived organic material, while the MBD supported a resource-replete microbiota that primarily metabolized dietary fiber. The objective of this work was to explore these findings more deeply using bioinformatic analyses of metatranscriptomic data. Our analysis showed increased transcription of fiber-degrading enzymes in the MBD and mucin-degrading enzymes in the WD. While in this analysis functional diversity of the gut microbiome was not affected, differences in resistant-starch and fiber content shifted the types of metabolic processes being actively transcribed. The MBD promoted biosynthetic and carbohydrate-fermenting pathways, while the WD was characterized by enzymes for host-glycan and protein degradation. Furthermore, the MBD-supported ecosystem benefits host health via enhanced SCFA production and reduced reliance on host glycan degradation. The WD fostered increased mucin and protein breakdown pathways that yield metabolites that may harm the gut barrier and systemic metabolism.

microbiology↗

Faecalibacterium prausnitzii, depleted in the Parkinson's disease microbiome, improves motor deficits in α-synuclein overexpressing mice

Gut microbiome composition is altered in Parkinsons disease (PD), a neurodegenerative disorder characterized by motor dysfunction and frequently accompanied by gastrointestinal (GI) symptoms. Notably, microbial taxa with anti-inflammatory properties are consistently depleted in PD patients compared to controls. To explore whether specific gut bacteria may be disease-protective, we assembled a microbial consortium of 8 human-associated taxa that are reduced in individuals with PD across multiple cohorts and geographies. Treatment of -synuclein overexpressing (Thy1-ASO) mice, an animal model of PD, with this consortium improved motor and GI deficits. A single bacterial species from this consortium, Faecalibacterium prausnitzii, was sufficient to correct gut microbiome deviations in Thy1-ASO mice, induce anti-inflammatory immune responses, and promote protective colonic gene expression profiles. Accordingly, oral treatment with F. prausnitzii robustly ameliorated motor and GI symptoms and reduced -synuclein aggregates in the brain. These findings support the emerging hypothesis of functional contributions by the microbiome to PD and embolden development of potential probiotic therapies.

physiology↗

Methanogens are associated with altered microbial production of short-chain fatty acids and human-host metabolizable energy

Methanogens are CH4-producing, H2-oxidizing (i.e. hydrogenotrophic) archaea. Numerous studies have associated methanogens with obesity, but these results have been inconsistent. One link to host metabolism may be methanogens ability to consume H2, thus reducing H2 partial pressure and thermodynamically enhancing fermentation of sugars to short-chain fatty acids (SCFA) that the host can absorb. Because research linking methanogenesis to human metabolism is limited, our goal with this exploratory analysis was to investigate relationships between methanogens and other hydrogenotrophs, and the association of methanogens with human metabolizable energy (ME). Using results from a randomized crossover feeding study with well-characterized human participants and novel continuous methane measurements, we analyzed hydrogenotroph abundance and activity, fecal and serum SCFAs, and host ME between high and low CH4 producers. Methanogens were detected in about one-half of participants, and most were high CH4 producers. We found no evidence that methanogens consumption of H2 to produce CH4 affected other hydrogenotrophs. High CH4 producers had greater serum propionate and host ME irrespective of diet, as well as greater gene and transcript abundance of a key enzyme of the H2-consuming, propionate-producing succinate pathway. Finally, a network analysis revealed positive relationships between Methanobrevibacter smithii (the most prevalent methanogen in the human colon) and bacteria capable of degrading fiber and fermenting fiber- degradation products, thus forming a trophic chain to extract additional energy from undigested substrates. Our results show that methanogens in a microbial consortium were linked to host metabolizable energy through enhanced SCFA production and host SCFA absorption.

microbiology↗