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1.
Mayo Clin Proc ; 96(6): 1418-1425, 2021 06.
Article in English | MEDLINE | ID: covidwho-1492380

ABSTRACT

OBJECTIVE: To report experience with fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (rCDI) and provide recommendations for management of rCDI and donor testing during the COVID-19 pandemic. METHODS: A retrospective study of patients with rCDI who underwent FMT from May 26, 2020, to September 30, 2020, with stool from well-screened donors with health and infectious screening and a newly implemented strategy for COVID-19 screening with every 2-week bookend testing with stool quarantine. Patients were followed up for development of rCDI and COVID-19. RESULTS: Of the 57 patients who underwent FMT for rCDI, 29 were tested for COVID-19 via nasopharyngeal polymerase chain reaction (PCR) and 22 via serology. All results were negative, except for 1 positive serology. Donor testing every 2 weeks for COVID-19 via serology and nasopharyngeal swab PCR was negative, except for 2 donors at 1 center who were excluded. Three patients had rCDI after FMT, and 1 underwent repeat FMT. One patient developed respiratory symptoms suggestive of COVID-19 and tested negative via nasopharyngeal PCR. Eleven patients who underwent COVID-19 testing for elective procedures or hospitalizations tested negative. No SARS-CoV-2 transmission was noted. CONCLUSIONS: With appropriate donor screening, FMT can be performed safely for rCDI during the COVID-19 pandemic. Development of a validated stool assay for SARS-CoV-2 will simplify this process further.


Subject(s)
COVID-19/epidemiology , Clostridioides difficile , Clostridium Infections/therapy , Fecal Microbiota Transplantation , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/prevention & control , Fecal Microbiota Transplantation/adverse effects , Fecal Microbiota Transplantation/methods , Female , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Young Adult
2.
United European Gastroenterol J ; 9(9): 1027-1038, 2021 11.
Article in English | MEDLINE | ID: covidwho-1460274

ABSTRACT

BACKGROUND: With increasing number of clinical trials relating to fecal microbiota transplantation (FMT), it is crucial to identify and recruit long-term, healthy, and regular fecal donors. OBJECTIVE: We aimed to report the outcomes of screening and recruitment of fecal donors for FMT. METHODS: Potential donors were recruited via advertisement through internal mass emails at a university. They were required to undergo a pre-screening telephone interview, a detailed questionnaire, followed by blood and stool investigations. RESULTS: From January 2017 to December 2020, 119 potential donors were assessed with 75 failed pre-screening. Reasons for failure included: inability to come back for regular and long-term donation (n = 19), high body mass index (n = 17), underlying chronic illness or on long-term medications (n = 11), being healthcare professionals (n = 10), use of antibiotics within 3 months (n = 5) and others (n = 13). Forty-four donors completed questionnaires and 11 did not fulfill the clinical criteria. Of the remaining 33 potential donors who had stool and blood tests, 21 failed stool investigations (19 extended-spectrum beta-lactamase [ESBL] organisms, one Clostridioides difficile, one C. difficile plus Methicillin Resistant Staphylococcus aureus), one failed blood tests (high serum alkaline phosphatase level), one required long-term medication and nine withdrew consent and/or lost to follow-up. In total, only one out of 119 (0.8%) potential donors was successfully recruited as a regular donor. CONCLUSION: There was a high failure rate in donor screening for FMT. Main reasons for screening failure included high prevalence of positive ESBL organisms in stool and failed commitment to regular stool donation.


Subject(s)
Donor Selection , Fecal Microbiota Transplantation , Adolescent , Adult , COVID-19 , Feces/microbiology , Female , Hong Kong , Humans , Male , Middle Aged , Pandemics , Prevalence , Young Adult , beta-Lactamases
3.
Ann Ist Super Sanita ; 57(3): 239-243, 2021.
Article in English | MEDLINE | ID: covidwho-1436209

ABSTRACT

Clostridioides (previously Clostridium) difficile infection (CDI) is a common cause of antibiotic-associated diarrhea, whose symptoms range from mild diarrhea to life-threatening pseudomembranous colitis. CDI is characterized by significant recurrence rate following initial resolution and recurrent C. difficile infection (rCDI) represents an onerous burden for the healthcare systems. Conventional antibiotic-based approaches are generally used for the treatment of rCDI but the effective therapy remains elusive. Recently, the faecal microbiota transplantation (FMT) has emerged as an alternative therapeutic strategy against rCDI, with high treatment success rate. In 2018, the Italian National FMT Program was launched, with the aim to provide high quality standards in FMT application to adults with rCDI not responding to antibiotic therapy. Here, we sketch out the key characteristics and the progress of the Italian National FMT Program during the COVID-19 pandemic.


Subject(s)
Clostridium Infections/therapy , Fecal Microbiota Transplantation , Adult , Aged , Aged, 80 and over , COVID-19 , Female , Humans , Italy , Male , Middle Aged , Prospective Studies , Young Adult
4.
J Pediatr Gastroenterol Nutr ; 73(4): 430-432, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1410091

ABSTRACT

ABSTRACT: Fecal microbiota transplantation (FMT) is currently the most effective but loosely regulated therapy, for recurrent Clostridioides difficile infection (rCDI) in pediatrics. Over the last 2 years, there have been mounting challenges in the ability to provide FMT to pediatric patients. Firstly, an Food and Drug Administration (FDA) safety alert in 2019 reported transmission of a multidrug resistant organism from FMT donor to recipient resulting in the death of 1 patient. Secondly, the coronavirus disease 2019 (COVID-19) pandemic induced further safety and regulatory challenges. Biotherapeutics are promising and more readily regulated treatment options for rCDI, which may replace FMT in the near future for adults upon regulatory agency approvals. Such approvals, however, are expected to be significantly delayed for children, raising concerns for limited access to effective treatment for children with rCDI. In this commentary, we discuss the recent challenges and future directions of FMT and microbial therapeutics in children with rCDI.


Subject(s)
COVID-19 , Clostridioides difficile , Clostridium Infections , Adult , Child , Clostridioides , Clostridium Infections/therapy , Fecal Microbiota Transplantation , Humans , Recurrence , SARS-CoV-2 , Treatment Outcome
5.
Ann Rheum Dis ; 80(9): 1158-1167, 2021 09.
Article in English | MEDLINE | ID: covidwho-1356912

ABSTRACT

OBJECTIVES: Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA). METHODS: In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26. RESULTS: Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)). CONCLUSIONS: In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA. TRIAL REGISTRATION NUMBER: NCT03058900.


Subject(s)
Arthritis, Psoriatic/therapy , Dysbiosis/therapy , Fecal Microbiota Transplantation/methods , Adult , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/microbiology , Female , Humans , Male , Methotrexate/therapeutic use , Middle Aged , Proof of Concept Study , Treatment Outcome
6.
J Pediatr Gastroenterol Nutr ; 73(4): 430-432, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1303996

ABSTRACT

ABSTRACT: Fecal microbiota transplantation (FMT) is currently the most effective but loosely regulated therapy, for recurrent Clostridioides difficile infection (rCDI) in pediatrics. Over the last 2 years, there have been mounting challenges in the ability to provide FMT to pediatric patients. Firstly, an Food and Drug Administration (FDA) safety alert in 2019 reported transmission of a multidrug resistant organism from FMT donor to recipient resulting in the death of 1 patient. Secondly, the coronavirus disease 2019 (COVID-19) pandemic induced further safety and regulatory challenges. Biotherapeutics are promising and more readily regulated treatment options for rCDI, which may replace FMT in the near future for adults upon regulatory agency approvals. Such approvals, however, are expected to be significantly delayed for children, raising concerns for limited access to effective treatment for children with rCDI. In this commentary, we discuss the recent challenges and future directions of FMT and microbial therapeutics in children with rCDI.


Subject(s)
COVID-19 , Clostridioides difficile , Clostridium Infections , Adult , Child , Clostridioides , Clostridium Infections/therapy , Fecal Microbiota Transplantation , Humans , Recurrence , SARS-CoV-2 , Treatment Outcome
8.
Int J Mol Sci ; 22(13)2021 Jun 25.
Article in English | MEDLINE | ID: covidwho-1285391

ABSTRACT

Metabolic syndrome (MetS) is a well-defined yet difficult-to-manage disease entity. Both the precipitous rise in its incidence due to contemporary lifestyles and the growing heterogeneity among affected populations present unprecedented challenges. Moreover, the predisposed risk for developing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in populations with MetS, and the viral impacts on host metabolic parameters, underscores the need to investigate this mechanism thoroughly. Recent investigations of metabolomics and proteomics have revealed not only differentially expressed substances in MetS, but also the consequences of diet consumption and physical activity on energy metabolism. These variations in metabolites, as well as protein products, also influence a wide spectrum of host characteristics, from cellular behavior to phenotype. Research on the dysregulation of gut microbiota and the resultant inflammatory status has also contributed to our understanding of the underlying pathogenic mechanisms. As for state-of-the-art therapies, advancing depictions of the bio-molecular landscape of MetS have emerged and now play a key role in individualized precision medicine. Fecal microbiota transplantation, aiming to restore the host's homeostasis, and targeting of the bile acid signaling pathway are two approaches to combatting MetS. Comprehensive molecular inquiries about MetS by omics measures are mandatory to facilitate the development of novel therapeutic modalities.


Subject(s)
Metabolic Syndrome/therapy , Animals , COVID-19/pathology , COVID-19/virology , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Humans , Metabolic Syndrome/metabolism , Metabolic Syndrome/pathology , Metabolomics , Precision Medicine , Proteomics , SARS-CoV-2/isolation & purification
9.
Clin Trials ; 18(5): 622-629, 2021 10.
Article in English | MEDLINE | ID: covidwho-1280562

ABSTRACT

INTRODUCTION: Clostridiodes difficile infection is the leading cause of infectious diarrhea in the United States, with substantial morbidity and mortality. Recurrent infection is especially challenging, with each recurrence increasing the likelihood of a successive recurrence, leading to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. Fecal microbiota transplantation to prevent recurrent infection is a promising intervention with a large effect size in observational studies, but with conflicting results from randomized controlled trials. We are conducting a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring at the participant's home. This type of trial design significantly improves trial efficiency, greatly decreases trial cost, increases consistency of trial administration, and most importantly makes nationwide clinical trials in less-common diseases possible. METHODS: This is a randomized comparison of capsule-delivered fecal microbiota transplant for the prevention of recurrent Clostridiodes difficile infection, administered after successful initial treatment of recurrent C. difficile infection with standard therapy. The primary endpoint is the incidence of recurrent C. difficile infection or death. Cases are identified by searching the Veterans Affairs Corporate Data Warehouse, with central study coordinators then reaching out to potential participants. Individuals meeting inclusion criteria and interested in participation are scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6 months. To mitigate risks of COVID-19, enrollment via video visits has been implemented. RESULTS: A total of 102 participants have been enrolled through January 2021. Centralized case identification and in-home enrollment has facilitated enrollment from 34 unique states, with 38% being from rural or highly rural areas. DISCUSSION: Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas.


Subject(s)
Anti-Bacterial Agents , Clostridioides difficile , Clostridium Infections/therapy , Fecal Microbiota Transplantation , Anti-Bacterial Agents/therapeutic use , COVID-19 , Humans , Microbiota , Quality of Life , Recurrence , Treatment Outcome
11.
Am J Gastroenterol ; 116(9): 1954-1956, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1278763

ABSTRACT

INTRODUCTION: The impact of the 2019 US Food and Drug Administration safety alert involving transmission of multidrug resistant organisms through fecal microbiota transplantation (FMT), and the COVID-19 pandemic on the use of FMT in children, is unknown. METHODS: A survey of pediatric gastroenterologists performing FMT for Clostridioides difficile infection was conducted. RESULTS: Of 36 respondents, 17 (47%) and 30 (83%) changed their FMT practices related to the US Food and Drug Administration safety alert and COVID-19 pandemic, respectively, with 22 (61%) of programs halted. DISCUSSION: The US Food and Drug Administration safety alert and COVID-19 pandemic have substantially influenced the availability and access of FMT for children.


Subject(s)
COVID-19 , Clostridium Infections/therapy , Fecal Microbiota Transplantation , Practice Patterns, Physicians' , SARS-CoV-2/isolation & purification , Child , Clostridium Infections/microbiology , Female , Humans , Male , Surveys and Questionnaires , United States
12.
Clin Transl Gastroenterol ; 12(6): e00363, 2021 06 09.
Article in English | MEDLINE | ID: covidwho-1262701

ABSTRACT

INTRODUCTION: 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. METHODS: A modified extraction method was used with an RT-PCR assay adapted from the Centers for Disease Control and Prevention PCR protocol for respiratory specimens. Contrived specimens were created using pre-COVID-19 banked stool specimens and spiking in known concentrations of SARS-CoV-2-specific nucleic acid. The highest transcript concentration at which 2/2 or 1/2 SARS-CoV-2 targets were detected in 9/10 replicates was defined as the dual-target limit and single-target limit of detection, respectively. The clinical performance of the assay was evaluated with stool samples collected from 17 nasopharyngeal swab RT-PCR-positive patients and 14 nasopharyngeal RT-PCR-negative patients. RESULTS: The dual-target and single-target limit of detection were 56 copies/µL and 3 copies/µL, respectively. SARS-CoV-2 was detected at concentrations as low as 0.6 copies/µL. Clinical stool samples from known COVID-19-positive patients demonstrated the detection of SARS-CoV-2 in stool up to 29 days from symptom onset with a high agreement with nasopharyngeal swab tests (kappa statistic of 0.95, P value < 0.001). DISCUSSION: The described RT-PCR test is a sensitive and flexible approach for the detection of SARS-CoV-2 in stool specimens. We propose an integrated screening approach that incorporates this stool test to support continuation of fecal microbiota transplantation programs.


Subject(s)
COVID-19 Testing/methods , COVID-19/transmission , Fecal Microbiota Transplantation/methods , Feces/virology , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , COVID-19 Testing/statistics & numerical data , Centers for Disease Control and Prevention, U.S./standards , Fecal Microbiota Transplantation/statistics & numerical data , Humans , Nasopharynx/virology , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2/isolation & purification , Tissue Donors/supply & distribution , United States
13.
Am J Gastroenterol ; 116(4): 647-656, 2021 04.
Article in English | MEDLINE | ID: covidwho-1257193

ABSTRACT

Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Clostridioides difficile/isolation & purification , Clostridium Infections/therapy , Fecal Microbiota Transplantation/methods , Clostridium Infections/microbiology , Feces/microbiology , Humans , Recurrence
14.
Front Immunol ; 12: 676232, 2021.
Article in English | MEDLINE | ID: covidwho-1247868

ABSTRACT

The intestinal microbiota is thought to be an important biological barrier against enteric pathogens. Its depletion, however, also has curative effects against some viral infections, suggesting that different components of the intestinal microbiota can play both promoting and inhibitory roles depending on the type of viral infection. The two primary mechanisms by which the microbiota facilitates or inhibits viral invasion involve participation in the innate and adaptive immune responses and direct or indirect interaction with the virus, during which the abundance and composition of the intestinal microbiota might be changed by the virus. Oral administration of probiotics, faecal microbiota transplantation (FMT), and antibiotics are major therapeutic strategies for regulating intestinal microbiota balance. However, these three methods have shown limited curative effects in clinical trials. Therefore, the intestinal microbiota might represent a new and promising supplementary antiviral therapeutic target, and more efficient and safer methods for regulating the microbiota require deeper investigation. This review summarizes the latest research on the relationship among the intestinal microbiota, anti-viral immunity and viruses and the most commonly used methods for regulating the intestinal microbiota with the goal of providing new insight into the antiviral effects of the gut microbiota.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/therapy , Fecal Microbiota Transplantation , Gastrointestinal Microbiome/immunology , Probiotics/therapeutic use , SARS-CoV-2/physiology , Virus Diseases/therapy , Animals , Host-Pathogen Interactions , Humans
15.
Dig Liver Dis ; 53(11): 1428-1432, 2021 11.
Article in English | MEDLINE | ID: covidwho-1240280

ABSTRACT

BACKGROUND: Due to the increasing rise of C. difficile infection, stool banks and donor programs have been launched to grant access to fecal microbiota transplantation (FMT). Our aim is to describe characteristics and outcomes of the donor program at our stool bank. METHODS: Donor candidates underwent a four-step selection process, including a clinical interview, blood and stool testing, a further questionnaire and a direct stool testing the day of each donation. From March 2020, specific changes to this process were introduced to avoid the potential transmission of COVID-19. We evaluated the rate of excluded candidates at each step of the screening, as well as the number of total fecal aliquots provided by qualified donors. RESULTS: Overall, 114 donor candidates were evaluated. Seventy-five candidates declined to join the program for logistic or personal issues, three were excluded after the questionnaire and seven for positive stool exams. Finally, 29 (25%) subjects qualified as stool donors, and provided 70 stool samples. Fifteen samples were excluded after direct molecular stool testing. A total of 127 aliquots was finally obtained. CONCLUSIONS: Donor recruitment for FMT is a challenging process, and only a small rate of candidates are eligible as donors.


Subject(s)
Biological Specimen Banks , Donor Selection/methods , Fecal Microbiota Transplantation , Adult , Biological Specimen Banks/organization & administration , Biological Specimen Banks/statistics & numerical data , Donor Selection/organization & administration , Donor Selection/statistics & numerical data , Feces/microbiology , Female , Humans , Infection Control/methods , Italy , Male , Program Evaluation , Prospective Studies
16.
Am J Health Syst Pharm ; 78(15): 1374-1381, 2021 07 22.
Article in English | MEDLINE | ID: covidwho-1182988

ABSTRACT

PURPOSE: There is a paucity of literature surrounding the use of early fecal microbiota transplantation (FMT) for patients presenting with an initial episode of severe, refractory Clostridioides difficile infection (CDI). Information on optimal antibiotic dosing and therapy duration surrounding FMT during an acute, initial episode of CDI is also limited. Described here is a case of successful treatment of CDI after 4 FMTs during an acute, initial episode of severe, refractory Clostridioides difficile colitis. SUMMARY: A 69-year-old community-dwelling, Caucasian male presented after 48 hours of vomiting and diarrhea. A stool sample was collected and resulted positive for Clostridioides difficile by both polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). The patient was treated with several days of oral and rectal vancomycin therapy in addition to intravenous metronidazole, but those treatments failed. His clinical and nutrition status deteriorated over the course of several days until salvage therapy was ordered, with administration of 1 inpatient nasogastric FMT and 1 inpatient colonoscopic FMT followed by outpatient colonoscopic FMTs on 2 consecutive days within 2 weeks of hospital discharge. CONCLUSION: This case suggests a role for early, repeat FMT during an initial presentation of a severe Clostridioides difficile colitis episode refractory to pharmacologic antimicrobial therapy. It also adds to emerging literature regarding the timing of antibiotic cessation surrounding FMT.


Subject(s)
Clostridioides difficile , Clostridium Infections , Colitis , Aged , Clostridioides , Clostridium Infections/diagnosis , Clostridium Infections/therapy , Colitis/therapy , Fecal Microbiota Transplantation , Humans , Male , Recurrence , Treatment Outcome
17.
Future Microbiol ; 16: 439-443, 2021 04.
Article in English | MEDLINE | ID: covidwho-1181329

ABSTRACT

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.


Subject(s)
COVID-19 , Clostridium Infections , Coinfection , Cross Infection/prevention & control , Feces , Pandemics/prevention & control , COVID-19/epidemiology , COVID-19/transmission , Clostridioides difficile/isolation & purification , Clostridium Infections/diagnosis , Clostridium Infections/epidemiology , Clostridium Infections/therapy , Coinfection/diagnosis , Coinfection/epidemiology , Fecal Microbiota Transplantation , Feces/microbiology , Feces/virology , Humans , Infection Control , SARS-CoV-2/isolation & purification
19.
Pharmacol Res ; 167: 105548, 2021 05.
Article in English | MEDLINE | ID: covidwho-1135540

ABSTRACT

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of agents, including Staphylococcal Enterotoxin B (SEB). Interestingly, a significant proportion of patients with COVID-19, also develop ARDS. In the absence of effective treatments, ARDS results in almost 40% mortality. Previous studies from our laboratory demonstrated that resveratrol (RES), a stilbenoid, with potent anti-inflammatory properties can attenuate SEB-induced ARDS. In the current study, we investigated the role of RES-induced alterations in the gut and lung microbiota in the regulation of ARDS. Our studies revealed that SEB administration induced inflammatory cytokines, ARDS, and 100% mortality in C3H/HeJ mice. Additionally, SEB caused a significant increase in pathogenic Proteobacteria phylum and Propionibacterium acnes species in the lungs. In contrast, RES treatment attenuated SEB-mediated ARDS and mortality in mice, and significantly increased probiotic Actinobacteria phylum, Tenericutes phylum, and Lactobacillus reuteri species in both the colon and lungs. Colonic Microbiota Transplantation (CMT) from SEB-injected mice that were treated with RES as well as the transfer of L. reuteri into recipient mice inhibited the production of SEB-mediated induction of pro-inflammatory cytokines such as IFN-γ and IL-17 but increased that of anti-inflammatory IL-10. Additionally, such CMT and L. reuteri recipient mice exposed to SEB, showed a decrease in lung-infiltrating mononuclear cells, cytotoxic CD8+ T cells, NKT cells, Th1 cells, and Th17 cells, but an increase in the population of regulatory T cells (Tregs) and Th3 cells, and increase in the survival of mice from SEB-mediated ARDS. Together, the current study demonstrates that ARDS induced by SEB triggers dysbiosis in the lungs and gut and that attenuation of ARDS by RES may be mediated, at least in part, by alterations in microbiota in the lungs and the gut, especially through the induction of beneficial bacteria such as L. reuteri.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Colon/drug effects , Enterotoxins , Fecal Microbiota Transplantation , Gastrointestinal Microbiome/drug effects , Lung/drug effects , Respiratory Distress Syndrome/prevention & control , Resveratrol/pharmacology , Superantigens , Animals , Cell Line , Colon/immunology , Colon/metabolism , Colon/microbiology , Cytokines/metabolism , Disease Models, Animal , Dysbiosis , Female , Inflammation Mediators/metabolism , Lactobacillus reuteri/drug effects , Lactobacillus reuteri/growth & development , Lung/immunology , Lung/metabolism , Lung/microbiology , Mice, Inbred C3H , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/microbiology
20.
Int J Mol Sci ; 22(6)2021 Mar 16.
Article in English | MEDLINE | ID: covidwho-1136501

ABSTRACT

COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut-lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.


Subject(s)
COVID-19/epidemiology , Fecal Microbiota Transplantation/methods , Pandemics , Clostridium Infections/therapy , Fecal Microbiota Transplantation/adverse effects , Gastrointestinal Microbiome , Humans , Lung/physiopathology , Treatment Outcome
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