Microbial determinants of effective donors in faecal microbiota transplantation for UC.

OBJECTIVE: Faecal microbiota transplantation (FMT) has variable efficacy in treating UC. Recently, oral lyophilised FMT was found to induce remission in patients with UC, with one donor having 100% efficacy compared with a second donor (36% efficacy). We characterised differences in the gut microbiota of these two donors with the aim of improving FMT donor selection. DESIGN: Faecal samples from the two donors were collected over a period of 44 (donor 1) or 70 (donor 2) weeks. The microbiome and metabolome were profiled using shotgun metagenomics and untargeted metabolomics RESULTS: Gut microbiome long-term stability was highly evident in the effective donor. Donor microbiota species evenness was a robust feature associated with clinical efficacy across two clinical trials of FMT in UC, leading to increased donor species engraftment in patients. Alpha diversity and beta diversity of donor gut microbiotas significantly differed. 90 bacterial species and one archaeon were differentially abundant between donors, 44 of which were >0.1% in relative abundance. 17/44 species were enriched in the effective donor, 11 of which (64.7%) were assembled into high-quality genomes that were prevalent (≥75% samples) in that donor, and six showed evidence of engraftment in patients. Taxonomic differences between donors translated to substantial microbial functional differences that were validated using metabolomics. CONCLUSION: Donor microbiota stability and species evenness were identified as novel metrics that were associated with therapeutic efficacy in UC, beyond individual microbial species or metabolites. These metrics may represent community resilience that translates to better engraftment in the host. TRIAL REGISTRATION NUMBER: ACTRN12619000611123.

Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19.

OBJECTIVE: Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus. METHODS: In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma. RESULTS: Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase. CONCLUSION: Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.

Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.

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.

Pneumatosis intestinalis in COVID-19.

INTRODUCTION: COVID-19 is a respiratory illness due to novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), described in December 2019 in Wuhan (China) and rapidly evolved into a pandemic. Gastrointestinal (GI) tract can also be involved. CASE PRESENTATION: A 44-year-old man was hospitalised for COVID-19-associated pneumonia. A rapid recovery of respiratory and general symptoms was observed after 1 week of treatment with lopinavir/ritonavir plus hydroxychloroquine and broad-spectrum antibiotics (piperacillin-tazobactam plus teicoplanin). No GI symptoms were reported during hospitalisation, but a lung contrast-enhancement CT (CE-CT) excluding thromboembolism showed, as collateral finding, intraperitoneal free bubbles not present on a previous CT examination; the subsequent abdominal CE-CT described pneumatosis intestinalis (PI) involving the caecum and the right colon. Ciprofloxacin plus metronidazole was started, and the 2-week follow-up CT showed the complete resolution of PI. DISCUSSION: The pathogenesis of PI is poorly understood. PI involving the caecum and right colon has been described for HIV and Cytomegalovirus infections, but, to our best knowledge, never before in COVID-19. We hypothesise a multifactorial aetiopathogenesis for PI, with a possible role of the bowel wall damage and microbiota impairment due to SARS-CoV-2 infection, and we suggest a conservative management in the absence of symptoms.