Browsing by Author "Kao, Dina"

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    Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway
    (Taylor & Francis, 2018-09-05) Monaghan, Tanya; Mullish, Benjamin H.; Patterson, Jordan; Wong, Gane KS; Marchesi, Julian R.; Xu, Huiping; Jilani, Tahseen; Kao, Dina
    The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.
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    Fecal Microbiota Transplantation for Severe or Fulminant Clostridioides difficile Infection: Systematic Review and Meta-analysis
    (Oxford University Press, 2021-07-23) Song, Yi Nong; Yang, David Yi; Veldhuyzen van Zanten, Sander; Wong, Karen; McArthur, Eric; Zhao Song, Claire; Ianiro, Gianluca; Cammarota, Giovanni; Kelly, Colleen; Fischer, Monika; Russell, Lindsey; Kao, Dina; Medicine, School of Medicine
    Background: Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI. Aim: This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI. Methods: A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates. Results: Two hundred and forty patients from 10 studies (8 case series, 1 case-control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low. Conclusion: FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.
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    Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience
    (Wiley, 2018) Cheng, Yao-Wen; Phelps, Emmalee; Ganapini, Vincent; Khan, Noor; Ouyang, Fangqian; Xu, Huiping; Khanna, Sahil; Tariq, Raseen; Friedman-Moraco, Rachel J.; Woodworth, Michael H.; Dhere, Tanvi; Kraft, Colleen S.; Kao, Dina; Smith, Justin; Le, Lien; El-Nachef, Najwa; Kaur, Nirmal; Kowsika, Sree; Ehrlich, Adam; Smith, Michael; Safdar, Nasia; Misch, Elizabeth Ann; Allegretti, Jessica R.; Flynn, Ann; Kassam, Zain; Sharfuddin, Asif; Vuppalanchi, Raj; Fischer, Monika; Medicine, School of Medicine
    Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti‐CDI antibiotics, respectively. Ninety‐four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT‐related adverse events (AE) occurred in 22.3% of cases, mainly comprising self‐limiting conditions including nausea, abdominal pain, and FMT‐related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT‐related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus‐seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non‐CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.
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    Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis
    (Elsevier, 2020) Cheng, Yao-Wen; Alhaffar, Dana; Saha, Srishti; Khanna, Sahil; Bohm, Matthew; Phelps, Emmalee; Ghabril, Marwan; Orman, Eric; Sashidhar, Sagi; Rogers, Nicholas; Xu, Huiping; Khoruts, Alexander; Vaughn, Byron; Kao, Dina; Wong, Karen; Cammarota, Giovanni; Ianiro, Gianluca; Dhere, Tanvi; Kraft, Colleen S.; Mehta, Nirja; Woodworth, Michael H.; Allegretti, Jessica R.; Nativ, Lotem; Marcus, Jenna; El-Nachef, Najwa; Fischer, Monika; Medicine, School of Medicine
    Background & Aims Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis. Methods We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT. Results Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child–Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00–152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81–78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)—most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death. Conclusions In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.
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    Impact of Fecal Microbiota Transplant Formulations, Storage Conditions, and Duration on Bacterial Viability, Functionality, and Clinical Outcomes in Patients with Recurrent Clostridioides difficile Infection
    (MDPI, 2025-03-04) Shaheen, Mohamed; McDougall, Chelsea; Chan, Leona; Franz, Rose; Wong, Karen; Giebelhaus, Ryland T.; Nguyen, Gwen; Nam, Seo Lin; de la Mata, A. Paulina; Yeo, Sam; Harynuk, James J.; Pakpour, Sepideh; Xu, Huiping; Kao, Dina; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    Fecal microbiota transplantation (FMT) is the most effective therapy for preventing recurrent Clostridioides difficile infection (rCDI). However, the impact of FMT formulations and storage conditions on bacterial viability, community structure, functionality, and clinical efficacy remains under-investigated. We studied the effect of different storage conditions on the bacterial viability (live/dead staining and cell sorting), community structure (16S rDNA analysis), and metabolic functionality (fermentation) of frozen and lyophilized FMT formulations. The clinical success rates of rCDI patients were correlated retrospectively with FMT formulations, storage durations, and host factors using the Edmonton FMT program database. Bacterial viability remained at 10-20% across various storage conditions and formulations and was comparable to that of fresh FMT. Live and dead bacterial fractions in both frozen and lyophilized FMT preparations exhibited distinct community structures. Storage durations, but not temperatures, negatively affected bacterial diversity. More short-chain fatty acids were found in the metabolomic profiling of in vitro fermentation products using lyophilized than frozen FMT. Clinical success rates in 537 rCDI patients receiving a single dose of FMT were not significantly different among the three formulations. However, longer storage durations and advanced recipient age negatively impacted clinical efficacy. Together, our findings suggest that FMT formulations and storage durations should be considered when establishing guidelines for product shelf life for optimal treatment outcomes.
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    Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic
    (BMJ Publishing Group, 2020-07-03) Ianiro, Gianluca; Mullish, Benjamin H.; Kelly, Colleen R.; Kassam, Zain; Kuijper, Ed J.; Ng, Siew C.; Iqbal, Tariq H.; Allegretti, Jessica R.; Bibbò, Stefano; Sokol, Harry; Zhang, Faming; Fischer, Monika; Costello, Samuel Paul; Keller, Josbert J.; Masucci, Luca; Prehn, Joffrey van; Quaranta, Gianluca; Quraishi, Mohammed Nabil; Segal, Jonathan; Kao, Dina; Satokari, Reetta; Sanguinetti, Maurizio; Tilg, Herbert; Gasbarrini, Antonio; Cammarota, Giovanni; Medicine, School of Medicine
    The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.
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    SARS-CoV-2 vaccines and donor recruitment for FMT
    (Elsevier, 2021) Ianiro, Gianluca; Mullish, Benjamin H.; Hvas, Christian Lodberg; Segal, Jonathan P.; Kuijper, Ed J.; Costello, Samuel P.; Kelly, Colleen R.; Allegretti, Jessica R.; Fischer, Monika; Iqbal, Tariq H.; Satokari, Reetta; Kao, Dina; van Prehn, Joffrey; Ng, Siew C.; Bibbò, Stefano; Dahl Baunwall, Simon Mark; Quraishi, Mohammed N.; Sokol, Harry; Zhang, Faming; Keller, Josbert; Masucci, Luca; Quaranta, Gianluca; Kassam, Zain; Sanguinetti, Maurizio; Tilg, Herbert; Gasbarrini, Antonio; Cammarota, Giovanni; Medicine, School of Medicine
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    Short-chain fatty and carboxylic acid changes associated with fecal microbiota transplant communally influence microglial inflammation
    (Elsevier, 2023-06-05) Churchward, Matthew A.; Michaud, Emily R.; Mullish, Benjamin H.; Blanco, Jesús Miguens; Garcia Perez, Isabel; Marchesi, Julian R.; Xu, Huiping; Kao, Dina; Todd, Kathryn G.; Biostatistics and Health Data Science, School of Medicine
    The intestinal microbiota has been proposed to influence human mental health and cognition through the gut-brain axis. Individuals experiencing recurrent Clostridioides difficile infection (rCDI) frequently report depressive symptoms, which are improved after fecal microbiota transplantation (FMT); however, mechanisms underlying this association are poorly understood. Short-chain fatty acids and carboxylic acids (SCCA) produced by the intestinal microbiota cross the blood brain barrier and have been proposed to contribute to gut-brain communication. We hypothesized that changes in serum SCCA measured before and after successful FMT for rCDI influences the inflammatory response of microglia, the resident immune cells of the central nervous system. Serum SCCA were quantified using gas chromatography-mass spectroscopy from 38 patients who participated in a randomized trial comparing oral capsule-vs colonoscopy-delivered FMT for rCDI, and quality of life was assessed by SF-36 at baseline, 4, and 12 weeks after FMT treatment. Successful FMT was associated with improvements in mental and physical health, as well as significant changes in a number of circulating SCCA, including increased butyrate, 2-methylbutyrate, valerate, and isovalerate, and decreased 2-hydroxybutyrate. Primary cultured microglia were treated with SCCA and the response to a pro-inflammatory stimulus was measured. Treatment with a combination of SCCA based on the post-FMT serum profile, but not single SCCA species, resulted in significantly reduced inflammatory response including reduced cytokine release, reduced nitric oxide release, and accumulation of intracellular lipid droplets. This suggests that both levels and diversity of SCCA may be an important contributor to gut-brain communication.
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    Stool Donor Body Mass Index Does Not Affect Recipient Weight After a Single Fecal Microbiota Transplantation for Clostridium difficile Infection
    (Elsevier, 2017) Fischer, Monika; Kao, Dina; Kassam, Zain; Smith, Justin; Louie, Thomas; Sipe, Brian; Torbeck, Michelle; Xu, Huiping; Ouyang, Fangqiang; Mozaffarian, Dariush; Allegretti, Jessica R.; Medicine, School of Medicine