Author
Monia Michaud
Bio: Monia Michaud is an academic researcher from Harvard University. The author has contributed to research in topics: Gut flora & Colitis. The author has an hindex of 18, co-authored 23 publications receiving 8522 citations.
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TL;DR: This study determined that short-chain fatty acids, gut microbiota–derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice, revealing that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
Abstract: Regulatory T cells (T regs ) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate T reg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic T regs . We determined that short-chain fatty acids, gut microbiota–derived bacterial fermentation products, regulate the size and function of the colonic T reg pool and protect against colitis in a Ffar2 -dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
3,733 citations
TL;DR: Data suggest that, through recruitment of tumor-infiltrating immune cells, fusobacteria generate a proinflammatory microenvironment that is conducive for colorectal neoplasia progression, and this work finds that F.nucleatum does not exacerbate colitis, enteritis, or inflammation-associated intestinal carcinogenesis.
1,704 citations
TL;DR: The composition of the microbiota in colorectal carcinoma is characterized using whole genome sequences from nine tumor/normal pairs and Fusobacterium sequences were enriched in carcinomas, confirmed by quantitative PCR and 16S rDNA sequence analysis of 95 carcinoma/normal DNA pairs.
Abstract: The tumor microenvironment of colorectal carcinoma is a complex community of genomically altered cancer cells, nonneoplastic cells, and a diverse collection of microorganisms. Each of these components may contribute to carcinogenesis; however, the role of the microbiota is the least well understood. We have characterized the composition of the microbiota in colorectal carcinoma using whole genome sequences from nine tumor/normal pairs. Fusobacterium sequences were enriched in carcinomas, confirmed by quantitative PCR and 16S rDNA sequence analysis of 95 carcinoma/normal DNA pairs, while the Bacteroidetes and Firmicutes phyla were depleted in tumors. Fusobacteria were also visualized within colorectal tumors using FISH. These findings reveal alterations in the colorectal cancer microbiota; however, the precise role of Fusobacteria in colorectal carcinoma pathogenesis requires further investigation.
1,527 citations
Weizmann Institute of Science1, Broad Institute2, Massachusetts Institute of Technology3, Harvard University4, Brigham and Women's Hospital5, Open University of Israel6, University of Texas MD Anderson Cancer Center7, Columbia University8, Tel Aviv University9, Sheba Medical Center10, University of Nebraska Medical Center11
TL;DR: By studying colon cancer models, it is found that bacteria can metabolize the chemotherapeutic drug gemcitabine into its inactive form, 2′,2′-difluorodeoxyuridine, seen primarily in Gammaproteobacteria.
Abstract: Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2',2'-difluorodeoxycytidine) into its inactive form, 2',2'-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin. Gemcitabine is commonly used to treat pancreatic ductal adenocarcinoma (PDAC), and we hypothesized that intratumor bacteria might contribute to drug resistance of these tumors. Consistent with this possibility, we found that of the 113 human PDACs that were tested, 86 (76%) were positive for bacteria, mainly Gammaproteobacteria.
923 citations
TL;DR: The presence of Klebsiella pneumoniae and Proteus mirabilis correlates with colitis in TRUC animals, and these TRUC-derived strains can elicit colitis but require a maternally transmitted endogenous microbial community for maximal intestinal inflammation.
713 citations
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TL;DR: A new method for metagenomic biomarker discovery is described and validates by way of class comparison, tests of biological consistency and effect size estimation to address the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities.
Abstract: This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.
9,057 citations
John N. Weinstein1, John N. Weinstein2, Eric A. Collisson3, Gordon B. Mills1 +376 more•Institutions (31)
TL;DR: The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA with a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages.
Abstract: The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.
5,294 citations
Journal Article•
TL;DR: The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels as mentioned in this paper.
Abstract: The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile.
4,634 citations
TL;DR: Data is reviewed supporting the diverse functional roles carried out by a major class of bacterial metabolites, the short-chain fatty acids (SCFAs), which affect various physiological processes and may contribute to health and disease.
3,363 citations
TL;DR: In high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses.
3,257 citations