Antibiotic‐Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant

Bajaj, Jasmohan S.; Kakiyama, Genta; Savidge, Tor; Takei, Hiroyuki; Kassam, Zain; Fagan, Andrew; Gavis, Edith; Pandak, William M.; Nittono, Hiroshi; Hylemon, Phillip B.; Boonma, Prapaporn; Haag, Anthony M.; Heuman, Douglas M.; Fuchs, Michael; John, Binu; Sikaroodi, Masoumeh; Gillevet, Patrick M.

doi:10.1002/hep.30037

Cited by 109 publications

(98 citation statements)

References 45 publications

(107 reference statements)

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“…This was paralleled by a decrease of systemic endotoxin levels [30]. Further metabolomics changes as consequence of rifaximin in patients with cirrhosis include a reduction in secondary/primary bile acid ratios and other indicators of microbiota metabolic function [27,31].…”

Section: Discussionmentioning

confidence: 95%

Long-Term Effect of Rifaximin with and without Lactulose on the Active Bacterial Assemblages in the Proximal Small Bowel and Faeces in Patients with Minimal Hepatic Encephalopathy

Schulz

Schütte

Vílchez-Vargas

et al. 2018

Dig Dis

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Background: Gut microbiota play an essential role in the pathogenesis of hepatic encephalopathy (HE). Treatment strategies are directed to modulate intestinal microbiota profiles and their function by the administration of the non-absorbable disaccharide lactulose and the non-absorbable antibiotic rifaximin, which are required for long terms, but little is known on their long-term effect on gut microbiota composition and function. Aim: To characterize the active bacterial assemblages in duodenum and faeces in patients with minimal HE (MHE) before, during and after long-term therapy with rifaximin. Methods: We analysed the microbiota composition in 5 patients with liver cirrhosis and MHE treated either with rifaximin 550 mg bid alone continuously for a period of 3 months or combined with lactulose 30–60 mL daily for 3 months. In addition to clinical assessments of HE, biopsies from duodenum and stool samples were analysed for their specific bacterial community applying NGS after RNA isolation before treatment, after 3 months of treatment and 3 months after the end of treatment. Results: All 5 patients had a significant improvement of their MHE. Bacterial communities were different and distinct in duodenal samples and faeces. No statistically significant changes were found in the bacterial community profile at the different time points. Conclusion: Rifaximin therapy with and without lactulose over a period of 3 months does not affect the bacterial community composition. The improvement of HE with rifaximin is lasting also after the end of treatment and therefore a prolonged effect on microbiota metabolic function is suggested.

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Section: Discussionmentioning

confidence: 95%

Long-Term Effect of Rifaximin with and without Lactulose on the Active Bacterial Assemblages in the Proximal Small Bowel and Faeces in Patients with Minimal Hepatic Encephalopathy

Schulz

Schütte

Vílchez-Vargas

et al. 2018

Dig Dis

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“…FMT was effective for these patients via inducing HBeAg clearance, suggesting that regulating intestinal microbiota might be beneficial to chronic hepatitis B treatment. A Phase I clinical trial demonstrated that FMT restored antibiotic‐induced microbial dysbiosis in patients with advanced liver cirrhosis . Even more, the effect of FMT on hepatic encephalopathy has been confirmed in both animal models and human beings.…”

Section: Fmt As a Possible Therapy For Various Type Of Cancers And Camentioning

confidence: 99%

Fecal microbiota transplantation in cancer management: Current status and perspectives

Chen

Jin

et al. 2018

Intl Journal of Cancer

223

161

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The human gut is home to a large and diverse microbial community, comprising about 1,000 bacterial species. The gut microbiota exists in a symbiotic relationship with its host, playing a decisive role in the host's nutrition, immunity and metabolism. Accumulating studies have revealed the associations between gut dysbiosis or some special bacteria and various cancers. Emerging data suggest that gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations with therapeutic intent has become a hot topic of cancer research, and the most dramatic manipulation of gut microbiota refers to fecal microbiota transplantation (FMT) from healthy individuals to patients. FMT has demonstrated remarkable clinical efficacy against Clostridium difficile infection (CDI) and it is highly recommended for the treatment of recurrent or refractory CDI. Lately, interest is growing in the therapeutic potential of FMT for other diseases, including cancers. We briefly reviewed the current researches about gut microbiota and its link to cancer, and then summarized the recent preclinical and clinical evidence to indicate the potential of FMT in cancer management as well as cancer‐treatment associated complications. We also presented the rationale of FMT for cancer management such as reconstruction of intestinal microbiota, amelioration of bile acid metabolism, and modulation of immunotherapy efficacy. This article would help to better understand this new therapeutic approach for cancer patients by targeting gut microbiota.

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“…secondary BAs increased and primary reduced, to baseline levels. Secondly, SCFAs that fell pre FMT were restored partly post FMT and lastly, the predicted functionality related to xenobiotic and lipid metabolism were higher after antibiotics, whereas bioenergetics, BA, Amino acids, glycans and vitamin/cofactor metabolism were higher post FMT 74 . Another phase 1 trial involving FMT via oral capsules in recurrent OHE has been completed ( NCT03152188) .…”

Section: Future Conceptsmentioning

confidence: 95%

Altered Microbiome in Patients With Cirrhosis and Complications

Acharya

Bajaj

2019

Clinical Gastroenterology and Hepatology

Self Cite

114

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The microbiome in cirrhosis is affected by multiple processes occurring at the level of the gut and systemically. This dysbiosis, or unfavorable microbiota profile, is present at several body sites and is associated with higher systemic inflammation, bacterial infections and poor outcomes. This increased morbidity in cirrhosis stems from an immune paralysis state that is partly related to the constant stimulation of the immune system by this dysbiosis. Dysbiosis as a dynamic event worsens with decompensation such as with hepatic encephalopathy, infections or acute-on-chronic liver failure (ACLF). These microbial patterns could be applied as diagnostic and prognostic measures in cirrhosis in the outpatient and inpatient setting. Current therapies for cirrhosis have differing impacts on gut microbial composition and functionality. Dietary modifications and the oral cavity have emerged as newer targetable factors to modulate the microbiome, which could affect inflammation and, potentially improve outcomes. Additionally, fecal microbial transplant is being increasingly studied to provide compositional and functional modulation of the microbiome. Ultimately, a combination of targeted therapies may be needed to provide an optimal gut milieu to improve outcomes in cirrhosis.

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Antibiotic‐Associated Disruption of Microbiota Composition and Function in Cirrhosis Is Restored by Fecal Transplant

Abstract: In patients with advanced cirrhosis on lactulose and rifaximin, FMT restored antibiotic-associated disruption in microbial diversity and function. (Hepatology 2018; 00:000-000).

Cited by 109 publications

References 45 publications

Long-Term Effect of Rifaximin with and without Lactulose on the Active Bacterial Assemblages in the Proximal Small Bowel and Faeces in Patients with Minimal Hepatic Encephalopathy

Long-Term Effect of Rifaximin with and without Lactulose on the Active Bacterial Assemblages in the Proximal Small Bowel and Faeces in Patients with Minimal Hepatic Encephalopathy

Fecal microbiota transplantation in cancer management: Current status and perspectives

Altered Microbiome in Patients With Cirrhosis and Complications

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