Author Correction: Gut microbiome structure and metabolic activity in inflammatory bowel disease

Franzosa, Eric A.; Sirota-Madi, Alexandra; Ávila-Pacheco, Julián; Fornelos, Nadine; Haiser, Henry J.; Reinker, Stefan; Vatanen, Tommi; Hall, Andrew Brantley; Mallick, Himel; McIver, Lauren J.; Sauk, Jenny; Wilson, Rebekah L.; Stevens, Betsy; Scott, Justine A; Pierce, Kerry A.; Deik, Amy; Bullock, Kevin; Imhann, Floris; Porter, Jeffrey A.; Zhernakova, Alexandra; Fu, Jingyuan; Weersma, Rinse K.; Wijmenga, Cisca; Clish, Clary B.; Vlamakis, Hera; Huttenhower, Curtis; Xavier, Ramnik J.

doi:10.1038/s41564-019-0442-5

Cited by 38 publications

(25 citation statements)

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“…Recently, the potential of metabolite-based therapeutic strategies or "postbiotics" as a method to treat microbial disruptions within the GI tract has been investigated. It is theorized that the intestinal microbiota of the gut impact host physiology through the secretion of small metabolites that modulate intricate cellular functions of the host organism [110][111][112]. The approach of this therapy is to not specifically target microbial composition in the gut but rather administer or inhibit metabolites in order to counteract the negative side effects of microbiome disruptions [113].…”

Section: Therapeutic Strategies For Chemotherapy-induced Inflammationmentioning

confidence: 99%

Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System

2021

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Breast Cancer is still one of the most common cancers today; however, with advancements in diagnostic and treatment methods, the mortality and survivorship of patients continues to decrease and increase, respectively. Commonly used treatments today consist of drug combinations, such as doxorubicin and cyclophosphamide; docetaxel, doxorubicin, and cyclophosphamide; or doxorubicin, cyclophosphamide, and paclitaxel. Although these combinations are effective at destroying cancer cells, there is still much to be understood about the effects that chemotherapy can have on normal organ systems such as the nervous system, gastrointestinal tract, and the liver. Patients can experience symptoms of cognitive impairments or “chemobrain”, such as difficulty in concentrating, memory recollection, and processing speed. They may also experience gastrointestinal (GI) distress symptoms such as diarrhea and vomiting, as well as hepatotoxicity and long term liver damage. Chemotherapy treatment has also been shown to induce peripheral neuropathy resulting in numbing, pain, and tingling sensations in the extremities of patients. Interestingly, researchers have discovered that this array of symptoms that cancer patients experience are interconnected and mediated by the inflammatory response.

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Section: Therapeutic Strategies For Chemotherapy-induced Inflammationmentioning

confidence: 99%

Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System

2021

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“…These results are similar to those reported by the literature [48,49] . In IBD, a decrease in Firmicutes and an increase in Proteobacteria have been reported [50][51][52] . Strikingly, a trend towards significant abundance of Firmicutes was found in UC patients (p = 0.051), being higher than in non-UC controls.…”

Section: Regarding Relative Abundance At Phylum Level Our Results Fomentioning

confidence: 98%

New insights in Ulcerative Colitis Associated Gut Microbiota in South American Population: Akkermansia and Collinsella, two distinctive genera found in Argentine subjects

Aguilera

Quesada

et al. 2020

Preprint

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Background Globally, ulcerative colitis (UC) is the most common form of intestinal inflammation, which is believed to be the result of a deregulated immune system response to commensal microbiota in a genetically susceptible host. Multicellular organisms rely heavily on their commensal symbiotic microbiota, whose composition is closely related to intrinsic local characteristics and regulated or modified by environmental factors. In the present study we aim to describe the unknown gut microbiota of patients with UC in comparison with healthy individuals in order to find novel biomarkers for UC in our region. Methods We evaluated 46 individuals, 26 healthy non-UC controls and 20 UC patients, from the metropolitan area of Buenos Aires (BA), Argentina. Clinical features, biochemical tests and anthropometric measurements were determined. Fecal samples were collected and DNA was extracted for microbiota analysis. The hypervariable regions V3-V4 of the bacterial 16SR gene were sequenced using a MiSeq platform and sequences were analyzed using the QIIME2 environment. In addition, we looked for differential functional pathways using PICRUSt and compared the performance of three machine learning models to discriminate the studied individuals, using taxa and functional annotations. Results All UC patients were under clinical treatment with 70% of individuals in remission. We found no significant differences in gut microbiota richness or evenness between UC patients and non-UC controls (alpha diversity). Remarcably, microbial compositional structure within groups (beta diversity) showed differences: At the phylum level, Verrucomicrobia was overrepresented in controls while Actinobacteria was distinctive of UC patients; At the genus level Bacteroides and Akkermancia were significantly more abundant among controls while Eubacterium and Collinsella in UC patients. In addition, our results showed that carbohydrates metabolism was preponderant in UC patients, not observing a distinctive biochemical pathway for the healthy non-UC controls. Finally, in order to define a robust classifying method in our population, we evaluated the capability of three machine learning models to classify individuals. Our results reinforced the idea of functional compensation in microbiome communities, as models that used KEGG orthologs annotations had better capabilities than taxonomy to distinguish UC patients. Conclusions Our study provides new knowledge on the differences and similarities of the gut microbiota of UC patients as compared to non-UC controls of our population. This allows not only the association of local changes in gut microbial diversity with the pathology process, but also the future development of personalized nutritional and pharmacological therapies through the use of omic strategies describing the metagenomic profiles of the Argentine population.

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“…We used two publicly available IBD metabolomics datasets for determining the differential abundance (DA) of bile acids in disease/dysbiotic conditions, specifically 1) the Prospective Registry in IBD Study at MGH (PRISM) 28 and 2) the IBDMDB study within the integrative Human Microbiome Project (HMP2) 29 . Additional multi-omic profiles from the HMP2 were further used to associate metabolite abundance with microbial species, gene products, and host gene expression.…”

Section: Data Overviewmentioning

confidence: 99%

“…Metabolomics profiles from the PRISM cohort were taken from the associated publication's supporting information 28 .…”

Section: Data Overviewmentioning

confidence: 99%

“…The finding that 3-oxoLCA and isoLCA exhibit T H 17-modulatory properties led us to consider the roles of these metabolites in the context of gut inflammation. Specifically, we examined metabolomic profiles of patients with Crohn's disease (CD) and ulcerative colitis (UC) in the cross-sectional Prospective Registry in IBD Study at MGH (PRISM) IBD cohort 28 and the longitudinal Integrative Human Microbiome Project (HMP2/ iHMP) IBD cohort 29 . Consistent with the function of 3-oxoLCA and isoLCA in our mouse data, levels of 3-oxoLCA and isoLCA were significantly decreased in CD patients (n=68) from the PRISM cohort relative to non-IBD controls (n = 34; linear model, FDR-corrected q-values =0.0392 and 0.0710, respectively).…”

Section: Differential Abundance Of Immunomodulatory Lca Metabolites Imentioning

confidence: 99%

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Human gut bacteria produce T_H17-modulating bile acid metabolites

Paik

Yao

Zhang

et al. 2021

Preprint

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The microbiota plays a pivotal role in gut immune homeostasis. Bacteria influence the development and function of host immune cells, including T helper cells expressing interleukin-17a (TH17 cells). We previously reported that the bile acid metabolite 3-oxolithocholic acid (3-oxoLCA) inhibits TH17 cell differentiation1. While it was suggested that gut-residing bacteria produce 3-oxoLCA, the identity of such bacteria was unknown. Furthermore, it was not clear whether 3-oxoLCA and other immunomodulatory bile acids are associated with gut inflammatory pathologies in humans. Using a high-throughput screen, we identified human gut bacteria and corresponding enzymes that convert the secondary bile acid lithocholic acid into 3-oxoLCA as well as the abundant gut metabolite isolithocholic acid (isoLCA). Like 3-oxoLCA, isoLCA suppressed TH17 differentiation by inhibiting RORγt (retinoic acid receptor-related orphan nuclear receptor γt), a key TH17 cell-promoting transcription factor. Levels of both 3-oxoLCA and isoLCA and the 3α-hydroxysteroid dehydrogenase (3α-HSDH) genes required for their biosynthesis were significantly reduced in patients with inflammatory bowel diseases (IBD). Moreover, levels of these bile acids were inversely correlated with expression of TH17 cell-associated genes. Overall, our data suggest that bacterially produced TH17 cell-inhibitory bile acids may reduce the risk of autoimmune and inflammatory disorders such as IBD.

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Author Correction: Gut microbiome structure and metabolic activity in inflammatory bowel disease

Abstract: In the Supplementary Tables 2, 4 and 6 originally published with this Article, the authors mistakenly included sample identifiers in the form of UMCGs rather than UMCG IBDs in the validation cohort; this has now been amended.

Cited by 38 publications

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Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System

Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System

New insights in Ulcerative Colitis Associated Gut Microbiota in South American Population: Akkermansia and Collinsella, two distinctive genera found in Argentine subjects

Human gut bacteria produce T_H17-modulating bile acid metabolites

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Author Correction: Gut microbiome structure and metabolic activity in inflammatory bowel disease

Abstract: In the Supplementary Tables 2, 4 and 6 originally published with this Article, the authors mistakenly included sample identifiers in the form of UMCGs rather than UMCG IBDs in the validation cohort; this has now been amended.

Cited by 38 publications

References 0 publications

Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System

Implications of Breast Cancer Chemotherapy-Induced Inflammation on the Gut, Liver, and Central Nervous System

New insights in Ulcerative Colitis Associated Gut Microbiota in South American Population: Akkermansia and Collinsella, two distinctive genera found in Argentine subjects

Human gut bacteria produce TH17-modulating bile acid metabolites

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Human gut bacteria produce T_H17-modulating bile acid metabolites