scholarly journals Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides

Science ◽  
2015 ◽  
Vol 350 (6256) ◽  
pp. aac5992 ◽  
Author(s):  
Meng Wu ◽  
Nathan P. McNulty ◽  
Dmitry A. Rodionov ◽  
Matvei S. Khoroshkin ◽  
Nicholas W. Griffin ◽  
...  

Libraries of tens of thousands of transposon mutants generated from each of four human gut Bacteroides strains, two representing the same species, were introduced simultaneously into gnotobiotic mice together with 11 other wild-type strains to generate a 15-member artificial human gut microbiota. Mice received one of two distinct diets monotonously, or both in different ordered sequences. Quantifying the abundance of mutants in different diet contexts allowed gene-level characterization of fitness determinants, niche, stability, and resilience and yielded a prebiotic (arabinoxylan) that allowed targeted manipulation of the community. The approach described is generalizable and should be useful for defining mechanisms critical for sustaining and/or approaches for deliberately reconfiguring the highly adaptive and durable relationship between the human gut microbiota and host in ways that promote wellness.

2019 ◽  
Vol 47 (06) ◽  
pp. 1381-1404 ◽  
Author(s):  
Jin Wang ◽  
Li Shao ◽  
Tai Rao ◽  
Wei Zhang ◽  
Wei-Hua Huang

Oplopanax elatus (Nakai) Nakai is an oriental herb, the polyyne-enriched fraction of which (PEFO) showed anticolorectal cancer (anti-CRC) effects. Other concomitant components, which are inevitably bio-transformed by gut microbiota after oral administration, might be interfere with the pharmacodynamics of polyynes. However, the influence of human gut microbiota on molecules from O. elatus possessing anticancer activity are yet unknown. In this study, the compounds in PEFO and PEFO incubated with human gut microbiota were analyzed and tentatively identified by HPLC-DAD-QTOF-MS. Two main polyynes ((3[Formula: see text]8[Formula: see text]-falcarindiol and oplopandiol) were not significantly decomposed, but some new unknown molecules were discovered during incubation. However, the antiproliferative effects of PEFO incubated with human gut microbiota for 72 h (PEFO I) were much lower than that of PEFO on HCT-116, SW-480, and HT-29 cells. Furthermore, PEFO possessed better anti-CRC activity in vivo, and significantly induced apoptosis of the CRC cells, which was associated with activation of caspase-3 according to the Western-blot results ([Formula: see text]). These results suggest anticolorectal cancer activity of polyynes might be antagonized by some bio-converted metabolites after incubation with human gut microbiota. Therefore, it might be better for CRC prevention if the polyynes could be orally administrated as purified compounds.


2013 ◽  
Vol 97 (2) ◽  
pp. 295-309 ◽  
Author(s):  
Lisa M Bode ◽  
Diana Bunzel ◽  
Melanie Huch ◽  
Gyu-Sung Cho ◽  
Denise Ruhland ◽  
...  

2013 ◽  
Vol 7 (10) ◽  
pp. 1933-1943 ◽  
Author(s):  
A Marcobal ◽  
P C Kashyap ◽  
T A Nelson ◽  
P A Aronov ◽  
M S Donia ◽  
...  

2020 ◽  
Author(s):  
Wei-Kai Wu ◽  
Suraphan Panyod ◽  
Po-Yu Liu ◽  
Chieh-Chang Chen ◽  
Hsien-Li Kao ◽  
...  

Abstract The capability of gut microbiota in degrading foods and drugs administered orally can result in diversified efficacies and toxicity interpersonally and cause significant impact on human health. Production of atherogenic trimethylamine N-oxide (TMAO) from carnitine is a gut microbiota-directed pathway and varies widely among individuals. Here we demonstrated a personalized TMAO formation and carnitine bioavailability from carnitine supplements by differentiating individual TMAO productivities with a recently developed oral carnitine challenge test (OCCT). By exploring gut microbiome in subjects characterized by TMAO producer phenotypes, we identified 39 operational taxonomy units that were highly correlated to TMAO productivity, including Emergencia timonensis, which has been recently discovered to convert γ-butyrobetaine to TMA in vitro. A microbiome-based random forest classifier was therefore constructed to predict the TMAO producer phenotype (AUROC = 0.81) which was then validated with an external cohort (AUROC = 0.80). A novel bacterium called Ihubacter massiliensis was also discovered to be a key microbe for TMA/TMAO production by using an OCCT-based humanized gnotobiotic mice model. Simply combining the presence of E. timonensis and I. massiliensis could account for 43% of high TMAO producers with 97% specificity. Collectively, this human gut microbiota phenotype-directed approach offers potential for developing precision medicine and provides insights into translational research.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sudeep Ghimire ◽  
Supapit Wongkuna ◽  
Ranjini Sankaranarayanan ◽  
Elizabeth P. Ryan ◽  
G. Jayarama Bhat ◽  
...  

Dietary fiber and flavonoids have substantial influence on the human gut microbiota composition that significantly impact health. Recent studies with dietary supplements such as quercetin and rice bran have shown beneficial impacts on the host alongside a positive influence of the gut microbiota. The specific bacterial species impacted by quercetin or rice bran in the diet is not well understood. In this study, we used a minibioreactor array system as a model to determine the effect of quercetin and rice bran individually, as well as in combination, on gut microbiota without the confounding host factors. We found that rice bran exerts higher shift in gut microbiome composition when compared to quercetin. At the species level, Acidaminococcus intestini was the only significantly enriched taxa when quercetin was supplemented, while 15 species were enriched in rice bran supplementation and 13 were enriched when quercetin and rice bran were supplemented in combination. When comparing the short chain fatty acid production, quercetin supplementation increased isobutyrate production while propionate dominated the quercetin and rice bran combined group. Higher levels of propionate were highly correlated to the lower abundance of the potentially pathogenic Enterobacteriaceae family. These findings suggest that the combination of quercetin and rice bran serve to enrich beneficial bacteria and reduce potential opportunistic pathogens. In vivo studies are necessary to determine how this synergy of quercetin and rice bran on microbiota impact host health.


PROTEOMICS ◽  
2015 ◽  
Vol 15 (20) ◽  
pp. 3474-3485 ◽  
Author(s):  
Alessandro Tanca ◽  
Antonio Palomba ◽  
Salvatore Pisanu ◽  
Maria Filippa Addis ◽  
Sergio Uzzau

Author(s):  
Thomas Gurry ◽  
Le Thanh Tu Nguyen ◽  
Xiaoqian Yu ◽  
Eric J Alm

AbstractThe human gut microbiota is known for its highly heterogeneous composition across different individuals. However, relatively little is known about functional differences in its ability to ferment complex polysaccharides. Through ex vivo measurements from healthy human donors, we show that individuals vary markedly in their microbial metabolic phenotypes (MMPs), mirroring differences in their microbiota composition, and resulting in the production of different quantities and proportions of Short Chain Fatty Acids (SCFAs) from the same inputs. We also show that aspects of these MMPs can be predicted from composition using 16S rRNA sequencing. From experiments performed using the same dietary fibers in vivo, we demonstrate that an ingested bolus of fiber is almost entirely consumed by the microbiota upon passage. We leverage our ex vivo data to construct a model of SCFA production and absorption in vivo, and argue that inter-individual differences in quantities of absorbed SCFA are directly related to differences in production. Taken together, these data suggest that personalized dietary fiber supplementation based on an individual’s MMP is an attractive therapeutic strategy for treating diseases associated with SCFA production.


2018 ◽  
Vol 59 ◽  
pp. 160-172 ◽  
Author(s):  
Alba C. Mayta-Apaza ◽  
Ellen Pottgen ◽  
Jana De Bodt ◽  
Nora Papp ◽  
Daya Marasini ◽  
...  

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