Browsing by Author "Gilbert, Jack A."

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    Decreased microbial co-occurrence network stability and SCFA receptor level correlates with obesity in African-origin women
    (Nature Research, 2018-11-20) Dugas, Lara R.; Bernabé, Beatriz Peñalver; Priyadarshini, Medha; Fei, Na; Park, Seo Jin; Brown, Laquita; Plange-Rhule, Jacob; Nelson, David; Toh, Evelyn C.; Gao, Xiang; Dong, Qunfeng; Sun, Jun; Kliethermes, Stephanie; Gottel, Neil; Luke, Amy; Gilbert, Jack A.; Layden, Brian T.; Microbiology and Immunology, School of Medicine
    We compared the gut microbial populations in 100 women, from rural Ghana and urban US [50% lean (BMI < 25 kg/m2) and 50% obese (BMI ≥ 30 kg/m2)] to examine the ecological co-occurrence network topology of the gut microbiota as well as the relationship of short chain fatty acids (SCFAs) with obesity. Ghanaians consumed significantly more dietary fiber, had greater microbial alpha-diversity, different beta-diversity, and had a greater concentration of total fecal SCFAs (p-value < 0.002). Lean Ghanaians had significantly greater network density, connectivity and stability than either obese Ghanaians, or lean and obese US participants (false discovery rate (FDR) corrected p-value ≤ 0.01). Bacteroides uniformis was significantly more abundant in lean women, irrespective of country (FDR corrected p < 0.001), while lean Ghanaians had a significantly greater proportion of Ruminococcus callidus, Prevotella copri, and Escherichia coli, and smaller proportions of Lachnospiraceae, Bacteroides and Parabacteroides. Lean Ghanaians had a significantly greater abundance of predicted microbial genes that catalyzed the production of butyric acid via the fermentation of pyruvate or branched amino-acids, while obese Ghanaians and US women (irrespective of BMI) had a significantly greater abundance of predicted microbial genes that encoded for enzymes associated with the fermentation of amino-acids such as alanine, aspartate, lysine and glutamate. Similar to lean Ghanaian women, mice humanized with stool from the lean Ghanaian participant had a significantly lower abundance of family Lachnospiraceae and genus Bacteroides and Parabacteroides, and were resistant to obesity following 6-weeks of high fat feeding (p-value < 0.01). Obesity-resistant mice also showed increased intestinal transcriptional expression of the free fatty acid (Ffa) receptor Ffa2, in spite of similar fecal SCFAs concentrations. We demonstrate that the association between obesity resistance and increased predicted ecological connectivity and stability of the lean Ghanaian microbiota, as well as increased local SCFA receptor level, provides evidence of the importance of robust gut ecologic network in obesity.
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    Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles
    (Springer Nature, 2023) Morton, James T.; Jin, Dong-Min; Mills, Robert H.; Shao, Yan; Rahman, Gibraan; McDonald, Daniel; Zhu, Qiyun; Balaban, Metin; Jiang, Yueyu; Cantrell, Kalen; Gonzalez, Antonio; Carmel, Julie; Frankiensztajn, Linoy Mia; Martin-Brevet, Sandra; Berding, Kirsten; Needham, Brittany D.; Zurita, María Fernanda; David, Maude; Averina, Olga V.; Kovtun, Alexey S.; Noto, Antonio; Mussap, Michele; Wang, Mingbang; Frank, Daniel N.; Li, Ellen; Zhou, Wenhao; Fanos, Vassilios; Danilenko, Valery N.; Wall, Dennis P.; Cárdenas, Paúl; Baldeón, Manuel E.; Jacquemont, Sébastien; Koren, Omry; Elliott, Evan; Xavier, Ramnik J.; Mazmanian, Sarkis K.; Knight, Rob; Gilbert, Jack A.; Donovan, Sharon M.; Lawley, Trevor D.; Carpenter, Bob; Bonneau, Richard; Taroncher-Oldenburg, Gaspar; Anatomy, Cell Biology and Physiology, School of Medicine
    Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella, Bifidobacterium, Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD.