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our research

Our team has spent a lot of time research the gut microbiome and its impact on human health. Below include a selected list of our peer-reviewed publications exploring this topic. If you are interested in collaborating with us, please view our Collaborate Page for current opportunities. All other inquiries can be directed to our Contact Us Page.

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featured work

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Risk factors and epidemiology of Clostridium difficile infection in hematopoietic stem cell transplant recipients during the peritransplant period
Hematopoietic stem cell transplant (HSCT) recipients represent a high-risk group for developing Clostridium difficile (CD) infection (CDI). We aimed to identify specific risk factors for CDI in an HSCT patient population during the peritransplant period. We performed a case-control study within a cohort of HSCT patients who received a transplant from November 2010 to March 2013. Cases had a clinical presentation compatible with CDI and a positive stool sample Xpert® C. difficile test. Controls were CDI negative and matched on age, gender, and transplant type. Peritransplant period was defined as -30 days or time of stem cell mobilization maneuver to 30 days post transplant in autologous SCT or 90 days post transplant in allogeneic SCT. Of 781 HSCTs performed during the study period, 650 (83.2%) had a stool sample submitted for CD testing. Eight-six (13.2%) cases with CDI were identified. Most of the cases were diagnosed within a week after transplantation (median of 5 days). In adjusted analysis, prior hospitalization (odds ratio [OR]: 2.01, 95% confidence interval [CI] 1.2-3.36), prior cephalosporin administration (OR 2.72, 95% CI: 1.54-4.83), and prior chemotherapy (OR: 3.26, 95% CI: 1.92-5.5) were significantly associated with CDI. Hospitalization, and prior antibiotic and chemotherapy use are risk factors that are not easily modifiable, which emphasizes the need to start investigating preventive or prophylactic strategies in this high-risk population.
Diverticulitis after fecal microbiota transplant for C. difficile infection.
Fecal microbiota transplantation (FMT) has become a cornerstone of the management of recurrent and refractory Clostridium difficile infection (CDI). Although it is safe and tolerable, adverse events have been reported with FMT via colonoscopy. Here we report the first case of diverticulitis occurring after an FMT for the treatment of recurrent CDI.
Use of standard donors in fecal microbiotal transplants.
Recurrent Clostridium difficile infection (CDI) is a growing epidemic with high recurrence rates after antibiotic treatment. Because of the limited number of medications available, alternative therapies such as fecal microbiota transplantation (FMT) are being closely studied for their role in the treatment of CDI. A systematic review of 27 case series and case reports has reported a 92% cure rate with the use of FMT for patients with recurrent CDI or pseudomembranous colitis with minimal adverse effects.
Fecal microbiota transplant protocol for clostridium difficile infection.
Fecal microbiota transplant has become more acceptable as a therapeutic for recurrent Clostridium difficile infection. The FDA has an enforcement discretion policy for practitioner's performing this therapy, which includes informed consent for this experimental treatment. This manuscript describes a typical procedure that can be followed that includes the important aspects of this preparation and treatment.
Fecal transplant is as effective and safe in immunocompromised as non-immunocompromised patients for Clostridium difficile.
Clostridium difficile infection (CDI) is a leading cause of nosocomial infection and is associated with significant morbidity and mortality. Immunocompromised (IC) patients are particularly at higher risk. Recurrence rates of up to 60 % have been reported after the third episode despite treatment with antibiotics. Recent published reports of fecal microbiota transplantation (FMT) in the IC population have shed light that the procedure proves to be effective and safe. No studies that compare the efficacy and adverse event rate of FMT between IC and non-IC patients currently exist The aim of our study is to compare the response and serious adverse event (SAE) rates of FMT for recurrent or refractory CDI (RCDI) between IC patients and non-IC patients.
Successful treatment of chronic Pouchitis utilizing fecal microbiota transplantation (FMT): a case report.
Fecal microbiota transplantation (FMT) is a novel therapy to transfer normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by disrupted homeostasis of intestinal microbiota or dysbiosis. FMT has been widely used in refractory Clostridium difficile infection (CDI) and recently it has gained popularity for treatment of inflammatory bowel disease (IBD). Previous studies suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotic achieved significant results for treating acute episodes of UC-associated pouchitis. However, currently there is no established effective treatment for chronic antibiotic-dependent or refractory pouchitis. In this report, we described a case of chronic antibiotic refractory pouchitis successfully treated with FMT through pouchoscopy. The effect has been sustainable at 6 months post-FMT.
Intestinal microbiome disruption in patients in a long-term acute care hospital: A case for development of microbiome disruption indices to improve infection prevention.
Long-term acute care hospital (LTACH) patients are a population with high antibiotic consumption,14 likely leading to severe intestinal microbiota disruption. In an effort to make a case for the potential impact of MDIs in improving infection control, we describe and compare the microbiomes from LTACH patients with prior antibiotic exposure, when individuals are most susceptible to MDRO colonization, to those of fecal microbiota transplant donors from a small pilot study, described below. We also examine associations between intestinal microbiome diversity, and clinical and demographic characteristics.
Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques.
An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT. The greatest microbiota shift was observed after antibiotic treatment. The bacterial community composition at 2 weeks post-FMT resembled the pre-FMT community structure, although differences in the abundances of minor bacterial populations remained. Immunologically, we observed significant increases in the number of peripheral Th17 and Th22 cells and reduced CD4(+) T cell activation in gastrointestinal tissues post-FMT. Importantly, the transplant was well tolerated with no negative clinical side effects. Although this pilot study did not control for the differential contributions of antibiotic treatment and FMT to the observed results, the data suggest that FMT may have beneficial effects that should be further evaluated in larger studies.
Fecal microbiota transplant for Clostridium difficile infection in older adults.
The objective of this study was to describe the safety of fecal microbiota transplant (FMT) for Clostridium difficile infection (CDI) among older adults. We performed a case review of all FMT recipients aged 65 or older treated at Emory University Hospital, a tertiary care and referral center for Georgia and surrounding states. We found that FMT is a generally safe and effective treatment option for older adults with CDI.
Laboratory Testing of Donors and Stool Samples for Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection.
Fecal microbiota transplantation is an efficacious and inexpensive therapy for recurrent Clostridium difficile infection, yet its safety is thought to depend on appropriate fecal donor screening. FDA guidance for regulation of this procedure is in flux, but screening and manufacture of fecal material from asymptomatic donors present many challenges to clinical laboratories. This minireview summarizes FDA regulatory changes, principles of donor selection, and recommended laboratory screening practices for fecal microbiota transplantation.
Challenges in fecal donor selection and screening for fecal microbiota transplantation: A review.
Fecal microbiota transplantation is best understood as an effective and inexpensive therapy for recurrent Clostridium difficile infection but fecal donor selection and screening should be periodically revised. Here, we review current recommendations for selection and screening of fecal donors for fecal microbiota transplantation. We recommend considering diabetes mellitus, prior cardiovascular events, and clinical healthcare exposure as fecal donor exclusion criteria until more is known about the association of these conditions with the human gut microbiome. We review the non-bacterial members of the human gut microbiome, associations of the gut microbiome with colorectal malignancies, the human gut resistome and how these may impact future donor screening recommendations. Collaboration between clinicians, clinical laboratory scientists, industry and regulatory agencies will be critically important for continued improvement in donor selection and screening.
Fecal Microbiota Transplant for Clostridium difficile Infection in a Pregnant Patient.
Clostridium difficile infection has been associated with negative outcomes in the general population and in pregnant patients. Fecal microbiota transplant has become the standard for treatment of recurrent as well as refractory C difficile infection. We present a case of a 28-year-old pregnant woman who presented with recurrent C difficile infection despite treatment with vancomycin and fidaxomicin and underwent a successful fecal microbiota transplant through colonoscopy at 18 weeks of gestation. She no longer required antibiotics for the remainder of her pregnancy to treat C difficile and had a term vaginal delivery at 39 weeks of gestation. Our pregnant patient tolerated and responded to a fecal microbiota transplant for treatment of recurrent C difficile infection. Future large-scale studies are needed to determine the efficacy, safety, and long-term effects of manipulating the microbiome in pregnant patients and the neonates.
The microbiome: current and future view of an ancient paradigm.
Current perspectives on the microbiome in health and disease
Ethical Considerations in Microbial Therapeutic Clinical Trials.
As understanding of the human microbiome improves, novel therapeutic targets to improve human health with microbial therapeutics will continue to expand. We outline key considerations of balancing risks and benefits, optimising access, returning key results to research participants, and potential conflicts of interest.
Durability and Long-term Clinical Outcomes of Fecal Microbiota Transplant Treatment in Patients With Recurrent Clostridium difficile Infection.
Fecal microbiota transplant (FMT) appears safe and effective for treatment of recurrent Clostridium difficile infection (RCDI). However, durability, long-term clinical outcomes, and patient satisfaction after FMT are not well described. In this follow-up survey of outcomes after FMT at a median of 22 months follow-up, 82% of patients had durable cure of CDI. Patients with recurrence had more post-FMT antibiotic exposure, underscoring the need for thoughtful antibiotic use and a potential role for prophylactic microbiome enrichment to reduce recurrence.
Fecal Microbiota Transplant for Multidrug-Resistant Organism Decolonization Administered During Septic Shock.
Antibiotic resistance (AR) is a growing crisis fueled by globalization and widespread antibiotic use.1 The development of new antibiotics has not matched the emergence of MDROs,2 making it further necessary to explore other avenues to combat this issue. Fecal microbiota transplantation (FMT) is one such option that needs further exploration in the acute-care setting in cases with therapeutic limitations associated with AR such as the following.
Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.
Fecal microbiota transplantation (FMT) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012-December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was -17.65 (95% CI -1.25 to 0.58) (ng/mL)/(mg/kg/d), P-value .43 by Wilcoxon signed-rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was -0.33 (95% CI -1.25 to 0.58) (ng/mL)/(mg/d), P-value .28 by Wilcoxon signed-rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT, with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed.
Fecal Microbiota Transplant for Refractory Clostridium difficile Infection Interrupts 25-Year History of Recurrent Urinary Tract Infections.
Here, we describe resolution of recurrent symptomatic UTI after FMT for RCDI in a woman who had been treated with nearly continuous antibiotics in the preceding 2 years. As common sources of morbidity, UTIs make significant contributions toward antibiotic resistance and antibiotic-associated infections. Though FMT may have changed provider behavior, post-FMT urine cultures were not indicated in the absence of further symptoms. Pre- or post-FMT stool cultures were not obtained for microbiota analysis. However, our case adds evidence for FMT as a safe and potentially efficacious intervention for the prevention and treatment of infections outside of C. difficile, suggesting a possible role for FMT in combatting antimicrobial resistance.
Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience.
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.
The Use of Microbiome Restoration Therapeutics to Eliminate Intestinal Colonization With Multidrug-Resistant Organisms.
Antibiotic resistance (AR) has been described by the World Health Organization as an increasingly serious threat to global public health. Many mechanisms of AR have become widespread due to global selective pressures such as widespread antibiotic use. The intestinal tract is an important reservoir for many multidrug-resistant organisms (MDROs), and next-generation sequencing has expanded understanding of the resistome, defined as the comprehensive sum of genetic determinants of AR. Intestinal decolonization has been explored as a strategy to eradicate MDROs with selective digestive tract decontamination and probiotics being notable examples with mixed results. This review focuses on fecal microbiota transplantation and the early evidence supporting its efficacy in decolonizing MDROs and potential mechanisms of action to reduce AR genes. Current evidence suggests that fecal microbiota transplantation may have promise in restoring healthy microbial diversity and reducing AR, and clinical trials are underway to better characterize its safety and efficacy.
Fecal Microbiota Transplantations: Where Are We, Where Are We Going, and What Is the Role of the Clinical Laboratory?
Fecal microbiota transplantation (FMT) is a medical procedure by which intestinal microorganisms are transferred to a patient as a therapeutic. FMTs can use microbiota from donors or from an autologous supply; these are referred to as allo- and auto-FMTs, respectively. FMTs are most commonly used for medically refractory or recurrent infections of Clostridioides (formerly Clostridium) difficile. C. difficile infections (CDIs) usually develop after broad-spectrum antibiotic usage that disrupts the normal intestinal microbiota, creating a niche permissive for C. difficile to flourish and cause a toxin-mediated illness. CDIs are routinely treated with oral antimicrobial therapy; however, relapse, and even multiple relapses, can occur after antimicrobials are stopped. An adjunct treatment option is FMT. While FMTs have been used to treat CDIs for over a decade, questions remain regarding their effectiveness, safety, regulatory oversight, and best practices. We have asked 5 experts with different roles in the field (including infectious diseases, laboratory medicine, industry, and public health) to share their thoughts on this important topic.
The gut microbiome's role in the development, maintenance, and outcomes of sepsis.
The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.
Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis.
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.
Fecal Microbiota Transplantation: Tales of Caution.
Microbiota-based therapies are generally considered safe and are the cornerstone of management of patients with recurrent Clostridioides difficile infection, with high success rates to prevent future recurrences. These therapies have evolved with several emerging modalities of delivering a diverse microbial consortium to a patient with reduced microbiome diversity. The most widely use modality is fecal microbiota transplantation (FMT). Despite more than a decade of discovery and research, FMT is still dependent on procurement of donor stool from well-screened healthy donors. A detailed informed consent with patients is of absolute necessity as unforeseen complications have happened, and this has been a longstanding aspect of the US Food and Drug Administration’s (FDA’s) enforcement discretion.
Gram-Negative Taxa and Antimicrobial Susceptibility after Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.
Fecal microbiota transplantation (FMT) has promising applications in reducing multidrug-resistant organism (MDRO) colonization and antibiotic resistance (AR) gene abundance. However, data on clinical microbiology results after FMT are limited. We examined the changes in antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after treatment with FMT for recurrent Clostridioides difficile infection (RCDI). We also examined whether a history of FMT changed health care provider behavior with respect to culture ordering and antibiotic prescription. Medical records for RCDI patients who underwent FMT at Emory University between July 2012 and March 2017 were reviewed retrospectively. FMT-treated patients with Gram-negative culture data in the 1-year period preceding and the 1-year period following FMT were included. Demographic and clinical data were abstracted, including CDI history, frequency of Gram-negative cultures, microbiological results, and antibiotic prescription in response to positive cultures in the period following FMT. Twelve patients were included in this case series. We pooled data from infections at all body sites and found a decrease in the number of total and Gram-negative cultures post-FMT. We compared susceptibility profiles across taxa given the potential for horizontal transmission of AR elements and observed increased susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, and the aminoglycosides. FMT did not drastically influence health care provider ordering of bacterial cultures or antibiotic prescribing practices. We observed a reduction in Gram-negative cultures and a trend toward increased antimicrobial susceptibility. This study supports further investigation of FMT as a means of improving antimicrobial susceptibility.
Critical Care Management of the Patient with Clostridioides difficile.
Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery.
The interplay of SARS-CoV-2 and Clostridioides difficile infection.
The COVID-19 pandemic has changed the way we practice medicine and lead our lives. In addition to pulmonary symptoms; COVID-19 as a syndrome has multisystemic involvement including frequent gastrointestinal symptoms such as diarrhea. Due to microbiome alterations with COVID-19 and frequent antibiotic exposure, COVID-19 can be complicated by Clostridioides difficile infection. Co-infection with these two can be associated with a high risk of complications. Infection control measures in hospitals is enhanced due to the COVID-19 pandemic which in turn appears to reduce the incidence of hospital-acquired infections such as C. difficile infection. Another implication of COVID-19 and its potential transmissibility by stool is microbiome-based therapies. Potential stool donors should be screened COVID-19 symptoms and be tested for COVID-19.
Validation of High-Sensitivity Severe Acute Respiratory Syndrome Coronavirus 2 Testing for Stool-Toward the New Normal for Fecal Microbiota Transplantation.
Mounting evidence demonstrates potential for fecal-oral transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The US Food and Drug Administration now requires SARS-CoV-2 testing of potential feces donors before the use of stool manufactured for fecal microbiota transplantation. We sought to develop and validate a high-sensitivity SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) procedure for testing stool specimens.
Fecal Microbiota Transplantation Donor Screening Updates and Research Gaps for Solid Organ Transplant Recipients.
In this review, we discuss stool donor screening considerations to mitigate potential risks of pathogen transmission through fecal microbiota transplant (FMT) in solid organ transplant (SOT) recipients. SOT recipients have a higher risk for Clostridioides difficile infection (CDI) and are more likely to have severe CDI. FMT has been shown to be a valuable tool in the treatment of recurrent CDI (RCDI); however, guidelines for screening for opportunistic infections transmitted through FMT are underdeveloped. We review reported adverse effects of FMT as they pertain to an immunocompromised population and discuss the current understanding and recommendations for screening found in the literature while noting gaps in research. We conclude that while FMT is being performed in the SOT population, typically with positive results, there remain many unanswered questions which may have major safety implications and warrant further study.
Earlier use of fecal transplant administration during hospitalization for Clostridioides difficile infection may improve outcome.
Earlier use of fecal transplant administration during hospitalization for Clostridioides difficile infection may improve outcome.
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