An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain ...incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.
Irritable bowel syndrome (IBS) is one of the functional gastrointestinal disorders characterized by chronic and/or recurrent symptoms of abdominal pain and irregular defecation. Changed gut ...microbiota has been proposed to mediate IBS; however, contradictory results exist, and IBS-specific microbiota, metabolites, and their interactions remain poorly understood. To address this issue, we performed metabolomic and metagenomic profiling of stool and serum samples based on discovery (n = 330) and validation (n = 101) cohorts. Fecal metagenomic data showed moderate dysbiosis compared with other diseases, in contrast, serum metabolites showed significant differences with greater power to distinguish IBS patients from healthy controls. Specifically, 726 differentially abundant serum metabolites were identified, including a cluster of fatty acyl-CoAs enriched in IBS. We further identified 522 robust associations between differentially abundant gut bacteria and fecal metabolites, of which three species including Odoribacter splanchnicus, Escherichia coli, and Ruminococcus gnavus were strongly associated with the low abundance of dihydropteroic acid. Moreover, dysregulated tryptophan/serotonin metabolism was found to be correlated with the severity of IBS depression in both fecal and serum metabolomes, characterized by a shift in tryptophan metabolism towards kynurenine production. Collectively, our study revealed serum/fecal metabolome alterations and their relationship with gut microbiome, highlighted the massive alterations of serum metabolites, which empower to recognize IBS patients, suggested potential roles of metabolic dysregulation in IBS pathogenesis, and offered new clues to understand IBS depression comorbidity. Our study provided a valuable resource for future studies, and would facilitate potential clinical applications of IBS featured microbiota and/or metabolites.
Developing new pharmaceuticals requires massive amounts of time, money and efforts. The key step is how to find a safe and effective entity for a disease condition and how to develop it as new drug ...effectively. Unfortunately, the FDA's rate of approving new entities has declined dramatically in the last three decades. There is a strong need to review the current strategy and to optimize process in developing new drugs, both to shorten the process and increase the success rate. Chinese medicine has used natural products to treat patients for thousands of years, and Chinese medicine practitioners have chronicled the patients and treatment methods for thousands of years. There is much information that has not yet been used. The success stories of artimisinin and arsentic trioxide are wonderful examples of how the annals of Chinese medicine can provide leads for discovering new drugs. This paper argues that the annals of Chinese medicine are valuable and describes how they can be used in modern drug discovery. The major topics addressed are: (i) why Chinese medicine is a rich resource for finding new drugs; (ii) how to identify a potential valuable record from Chinese medicine annals; (iii) when a potential valuable record is identified from annals, how to proceed; and (iv) both why and how the approach used for chemical drugs should be revised for drugs based on the historical documents related to herbal medicine. In conclusion, we argue here that the annals of Chinese medicine offer not only a rich resource for new drugs, but also several centuries of patient data with regard to safety and efficacy, that in effect represent pilot studies. Acknowledging and using these data can shorten new drug discovery time and improve efficiency of the drug development process, bringing more effective, safe drugs to market much more quickly and cheaply.
The reporting standards for randomized controlled trials were first published in 1996 by a group of scientists under the name "CONSORT," which means consolidated standards of reporting trials. ...Revisions followed in 2001 and 2010. A draft of the CONSORT for traditional Chinese medicine (TCM) was published in both Chinese and English in 2007. After publication of the draft, comments were solicited from the medical community. Some papers did raise concerns about which items should be included in the CONSORT for TCM such as the rationale of the trial design, intervention, outcome assessment, and adverse events. We have now reached the next step which is the finalization of the CONSORT for TCM. Three tasks remain. First, the major changes in CONSORT statement 2010 should be integrated into the CONSORT for TCM. Second, Chinese drugs from minerals and animals should be included in the guidelines. Finally, agreement must be reached among the working groups. Once the draft is finalized, wide dissemination and co-publication will be considered.
Using Chinese Materia Medica (CM) as injections is an innovation that is proving effective in extensive clinical use in Mainland China. However, recent reports have focused on adverse reactions, ...ignoring the considerable successes of these preparations. In order to achieve balance in the media and in the minds of the public, we suggest the first step is to clarify the concepts of and differences between adverse drug reactions (ADR) and adverse events (AE) for all concerned-the public, medical practitioners, government officials, and lawmakers. Second, the State Food and Drug Administration should raise the requirements for Chinese Materia Medica Injection (CMI) registration and license approval and emphasize the importance of evidence-based CMI development and evidence-based CMI license approval. Thirdly, drug companies and institutions should reinforce basic research about the quality control of herbs and CMI-drug interactions. Fourth, the Government should clarify the legal responsibilities for CMI approval agencies, CMI developers, medical doctors, and patients. Fifth, the medical association and Government should enhance training for health care professionals concerning the usage of CMIs. And finally sixth, State Food and Drug Administration should monitor the content and quality of the directions for use of CMI.
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