ORCID Profile
0000-0002-3739-8994
Current Organisations
Hong Kong Baptist University
,
Shanghai Jiao Tong University
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Publisher: Proceedings of the National Academy of Sciences
Date: 12-02-2008
Abstract: Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiome) and in idual variations in the microbiome influence host health, may be implicated in disease etiology, and affect drug metabolism, toxicity, and efficacy. However, the molecular basis of these microbe–host interactions and the roles of in idual bacterial species are obscure. We now demonstrate a“transgenomic” approach to link gut microbiome and metabolic phenotype (metabotype) variation. We have used a combination of spectroscopic, microbiomic, and multivariate statistical tools to analyze fecal and urinary s les from seven Chinese in iduals (s led twice) and to model the microbial–host metabolic connectivities. At the species level, we found structural differences in the Chinese family gut microbiomes and those reported for American volunteers, which is consistent with population microbial cometabolic differences reported in epidemiological studies. We also introduce the concept of functional metagenomics, defined as “the characterization of key functional members of the microbiome that most influence host metabolism and hence health.” For ex le, Faecalibacterium prausnitzii population variation is associated with modulation of eight urinary metabolites of erse structure, indicating that this species is a highly functionally active member of the microbiome, influencing numerous host pathways. Other species were identified showing different and varied metabolic interactions. Our approach for understanding the dynamic basis of host–microbiome symbiosis provides a foundation for the development of functional metagenomics as a probe of systemic effects of drugs and diet that are of relevance to personal and public health care solutions.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 08-06-2012
Abstract: The composition and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.
Publisher: Springer Science and Business Media LLC
Date: 27-03-2017
DOI: 10.1038/SREP45232
Abstract: Emerging evidence points to a strong association between sex and gut microbiota, bile acids (BAs), and gastrointestinal cancers. Here, we investigated the mechanistic link between microbiota and hepatocellular carcinogenesis using a streptozotocin-high fat diet (STZ-HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) murine model and compared results for both sexes. STZ-HFD feeding induced a much higher incidence of HCC in male mice with substantially increased intrahepatic retention of hydrophobic BAs and decreased hepatic expression of tumor-suppressive microRNAs. Metagenomic analysis showed differences in gut microbiota involved in BA metabolism between normal male and female mice, and such differences were lified when mice of both sexes were exposed to STZ-HFD. Treating STZ-HFD male mice with 2% cholestyramine led to significant improvement of hepatic BA retention, tumor-suppressive microRNA expressions, microbial gut communities, and prevention of HCC. Additionally the sex-dependent differences in BA profiles in the murine model can be correlated to the differential BA profiles between men and women during the development of HCC. These results uncover distinct male and female profiles for gut microbiota, BAs, and microRNAs that may contribute to sex-based disparity in liver carcinogenesis, and suggest new possibilities for preventing and controlling human obesity-related gastrointestinal cancers that often exhibit sex differences.
Publisher: American Chemical Society (ACS)
Date: 04-03-2022
Publisher: Oxford University Press (OUP)
Date: 13-07-2010
DOI: 10.1111/J.1574-6941.2010.00924.X
Abstract: This study monitored structural shifts of gut microbiota of rats developing precancerous mucosal lesions induced by carcinogen 1,2-dimethyl hydrazine (DMH) treatment using PCR-denaturing gradient gel electrophoresis (DGGE) and 454 pyrosequencing on the 16S rRNA gene V3 region. Partial least square discriminant analysis of DGGE fingerprints showed that the gut microbiota structure of treated animals was similar to that of the controls 1 and 3 weeks after DMH treatments, but significantly different 7 weeks after DMH treatments, when a large number of aberrant crypt foci (ACF) developed in their colons. Martens' uncertainty test, followed by anova test (P<0.05) identified Ruminococcus-like and Allobaculum-like bacteria as key variables for discrimination of DMH-treated rats from controls. Real-time PCR confirmed the significant increase of the Ruminococcus obeum and the Allobaculum-like bacteria in DMH-treated rats. UniFrac analysis based on V3 pyrosequencing further validated that the gut microbiota structures of treated and control animals were similar at an early stage, but segregated after ACF formation. Thirteen operational taxonomic units including Ruminococcus-like and Allobaculum-like bacteria were identified as key variables for the discrimination of DMH-treated rats from controls. Dynamic analysis of gut microbiota may become a noninvasive strategy for monitoring host health changes induced by carcinogen exposure.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 03-04-2013
Publisher: American Association for the Advancement of Science (AAAS)
Date: 13-02-2013
DOI: 10.1126/SCITRANSLMED.3005114
Abstract: Melamine is converted to cyanuric acid by the gut microbe Klebsiella , leading to melamine-cyanurate-urate coprecipitation that is associated with nephrotoxicity.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 06-06-2012
DOI: 10.1126/SCITRANSLMED.3004244
Abstract: Abnormal microbial-host metabolic interactions underlying disease provide new targets for therapeutic intervention.
Publisher: Springer Science and Business Media LLC
Date: 02-2008
DOI: 10.1038/NRD2505
Publisher: American Chemical Society (ACS)
Date: 24-10-2011
DOI: 10.1021/PR2007945
Abstract: Gut microbiota are associated with essential various biological functions in humans through a "network" of microbial-host co-metabolism to process nutrients and drugs and modulate the activities of multiple pathways in organ systems that are linked to different diseases. The microbiome impacts strongly on the metabolic phenotypes of the host, and hence, metabolic readouts can give insights into functional metagenomic activity. We applied an untargeted mass spectrometry (MS) based metabonomics approach to profile normal Wistar rats exposed to a broad spectrum β-lactam antibiotic imipenem/cilastatin sodium, at 50 mg/kg/daily for 4 days followed by a 14-day recovery period. In-depth metabolic phenotyping allowed identification of a panel of 202 urinary and 223 fecal metabolites significantly related to end points of a functional metagenome (p < 0.05 in at least one day), many of which have not been previously reported such as oligopeptides and carbohydrates. This study shows extensive gut microbiota modulation of host systemic metabolism involving short-chain fatty acids, tryptophan, tyrosine metabolism, and possibly a compensatory mechanism of indole-melatonin production. Given the integral nature of the mammalian genome and metagenome, this panel of metabolites will provide a new platform for potential therapeutic markers and mechanistic solutions to complex problems commonly encountered in pathology, toxicology, or drug metabolism studies.
Publisher: American Chemical Society (ACS)
Date: 26-08-2014
DOI: 10.1021/PR500434S
Publisher: American Chemical Society (ACS)
Date: 02-04-2021
Publisher: Springer Science and Business Media LLC
Date: 21-02-2022
DOI: 10.1186/S40168-021-01208-5
Abstract: Gut microbiota contributes to colorectal cancer (CRC) pathogenesis through microbes and their metabolites. The importance of microbiota-associated metabolites in colorectal carcinogenesis highlights the need to investigate the gut metabolome along the adenoma-carcinoma sequence to determine their mechanistic implications in the pathogenesis of CRC. To date, how and which microbes and metabolites interactively promote early events of CRC development are still largely unclear. We aim to determine gut microbiota-associated metabolites and their linkage to colorectal carcinogenesis. We performed metabolomics and metagenomics profiling on fecal s les from 386 subjects including 118 CRC patients, 140 colorectal adenomas (CRA) patients and 128 healthy subjects as normal controls (NC). We identified differences in the gut metabolite profiles among NC, CRA and CRC groups by partial least squares-discriminant and principal component analyses. Among the altered metabolites, norvaline and myristic acid showed increasing trends from NC, through CRA, to CRC. CRC-associated metabolites were enriched in branched-chain amino acids, aromatic amino acids and aminoacyl-tRNA biosynthesis pathways. Moreover, metabolites marker signature (twenty metabolites) classified CRC from NC subjects with an area under the curve (AUC) of 0.80, and CRC from CRA with an AUC of 0.79. Integrative analyses of metabolomics and metagenomics profiles demonstrated that the relationships among CRC-associated metabolites and bacteria were altered across CRC stages certain associations exhibited increasing or decreasing strengths while some were reversed from negative to positive or vice versa. Combinations of gut bacteria with the metabolite markers improved their diagnostic performances CRC vs NC, AUC: 0.94 CRC vs CRA, AUC 0.92 and CRA vs NC, AUC: 0.86, indicating a potential for early diagnosis of colorectal neoplasia. This study underscores potential early-driver metabolites in stages of colorectal tumorigenesis. The Integrated metabolite and microbiome analysis demonstrates that gut metabolites and their association with gut microbiota are perturbed along colorectal carcinogenesis. Fecal metabolites can be utilized, in addition to bacteria, for non-invasive diagnosis of colorectal neoplasia.
Publisher: Elsevier BV
Date: 11-2020
Location: United States of America
No related grants have been discovered for Wei Jia.