BackgroundLong-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear.ObjectiveTo investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus.MethodsWe conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months.ResultsAt 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii. Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including Clostridium innocuum and Actinomyces naeslundii (all p<0.05). Butyrate-producing bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlations with PACS at 6 months.ConclusionThese findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.

The incidence of inflammatory bowel diseases (IBD) in East has risen over the past decade to become a global disease. The increasing number of studies on the incidence and course of IBD in East has enabled us to explore East versus West differences in the epidemiology of IBD which could enhance our understanding of the heterogeneity of the disease and eventually assist in the discovery of novel therapeutic targets and design of preventive strategies. Comparison of population‐based data in East and West reveals that the incidence of IBD has risen rapidly in East while plateauing in West. Furthermore, the clinical presentation and course of IBD differs between East and West with more patients in East presenting with complicated disease. Considering the scarcity of population‐based data from East and the lack of studies with long durations of follow‐up, it remains to be clarified whether these differences reflect true differences in disease presentation. The effects of genetic and environmental risk factors contributing to IBD also differ between Eastern and Western populations. Considering the differential effects of genetic and environmental risk factors in East and West, future studies should seek to discover novel genetic and environmental risk factors which might specifically apply to eastern populations. In this narrative review, we compare the epidemiology of IBD between eastern and western countries by summarizing evidence from population‐based cohort studies in the last ten years. Furthermore, we look at differences in genetic susceptibility and environmental triggers of IBD between East and West.

ObjectiveThe impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).DesignIn this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.ResultsProportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in Bifidobacterium and Lactobacillus compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05).ConclusionRepeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients’ microbiota and improvement in lipid profile and liver stiffness.Trial registration numberNCT03127696.

Worldwide, the incidence of motor neuron disease (MND) has been increasing steadily over recent decades. We reported a follow-up epidemiology study of MND in this locality. We identified the subjects from the computer database of the government hospital system between 1 January 1997 and 31 January 2002 by searching the ICD code starting from 335.xx. Every retrieved case or their records were reviewed and validated by neurologist(s) of the responsible regional hospitals which the patients attended. One hundred and twenty cases from seven regional hospitals (serving 48.05% of the HKSAR population) were identified, validated and confirmed to be MND or related diseases. Ninety-eight new cases were diagnosed during the study period. Average age of onset was 58.76 years; SD 14.12 (28-89) years. Male to female ratio was 1.72:1. Peak age of onset was 60-64 years without sex difference. The adjusted incidence rate was 0.60/100,000/year. The adjusted point prevalence at the prevalence date (31 January 2001) was 3.04/100,000. Despite the incidence and prevalence of MND among Hong Kong Chinese, it remained low compared to worldwide figures, and our data suggested a significant rise of MND or related disease in the last decade. A territory-wide prospective epidemiological study is indicated.

SummaryBackgroundPsychiatric co‐morbidities including depression and anxiety are common in inflammatory bowel diseases (IBD). Emerging evidence suggests that interactions between the gut microbiota and brain may play a role in the pathogenesis of psychiatric symptoms in IBD.AimTo review the literature on microbiota‐brain‐gut interactions in gut inflammation, psychosocial stress and mental disorders and to discuss the putative mediating role of gut microbiota in the development of psychiatric symptoms or co‐morbidities in IBD.MethodsA literature search was conducted on Ovid and Pubmed to select relevant animal and human studies reporting an association between IBD, mental disorders and gut microbiota.ResultsGut microbial alterations are frequently reported in subjects with IBD and with mental disorders. Both have been associated with reduced faecal bacterial diversity, decreased taxa within the phylum Firmicutes and increased Gammaproteobacteria. In animal studies, microbial perturbations induce behavioural changes and modulate inflammation in mice. Anxiety‐ and depression‐like behaviours in animals can be transferred via faecal microbiota. In humans, modulation of the gut microbiota with probiotics is associated with behavioural and mood changes. Recent data show correlations in changes of faecal and mucosal microbiota and psychological distress in patients with IBD independent of disease activity.ConclusionBoth IBD and mental disorders are associated with gut microbial alterations. Preclinical and preliminary human studies have shown a mediating role of the gut microbiota in intestinal inflammation and anxiety, depression and stress. Targeting the gut microbiota may represent a useful therapeutic approach for the treatment of psychiatric co‐morbidities in IBD.

Background and Aim Gut dysbiosis is associated with immune dysfunction and severity of COVID‐19. Whether targeting dysbiosis will improve outcomes of COVID‐19 is unknown. This study aimed to assess the effects of a novel gut microbiota‐derived synbiotic formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID‐19 patients. Methods This was an open‐label, proof‐of‐concept study. Consecutive COVID‐19 patients admitted to an infectious disease referral center in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID‐19 patients and healthy population. COVID‐19 patients who were admitted under another independent infectious disease team during the same period without receiving SIM01 acted as controls. All patients received standard treatments for COVID‐19 according to the hospital protocol. We assessed antibody response, plasma proinflammatory markers, nasopharyngeal SARS‐CoV‐2 viral load, and fecal microbiota profile from admission up to week 5. Results Twenty‐five consecutive COVID‐19 patients received SIM01 for 28 days; 30 patients who did not receive the formula acted as controls. Significantly more patients receiving SIM01 than controls developed SARS‐CoV‐2 IgG antibody (88% vs 63.3%; P = 0.037) by Day 16. One (4%) and 8 patients (26.7%) in the SIM01 and control group, respectively, failed to develop positive IgG antibody upon discharge. At week 5, plasma levels of interleukin (IL)‐6, monocyte chemoattractant protein‐1 (MCP‐1), macrophage colony‐stimulating factor (M‐CSF), tumor necrosis factor (TNF‐α), and IL‐1RA reduced significantly in the SIM01 but not in the control group. There was a significant negative correlation of nasopharyngeal SARS‐CoV‐2 viral load and SIM01 intervention. Metagenomic analysis showed that bacterial species in SIM01 formula were found in greater abundance leading to enrichment of commensal bacteria and suppression of opportunistic pathogens in COVID‐19 patients by week 4 and week 5. Conclusions This proof‐of‐concept study suggested that the use of a novel gut microbiota‐derived synbiotic formula, SIM01, hastened antibody formation against SARS‐CoV‐2, reduced nasopharyngeal viral load, reduced pro‐inflammatory immune markers, and restored gut dysbiosis in hospitalised COVID‐19 patients.

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.

BackgroundThere were limited data on the risk of post-polypectomy bleeding (PPB) in patients on direct oral anticoagulants (DOAC). We aimed to evaluate the PPB and thromboembolic risks among DOAC and warfarin users in a population-based cohort.MethodsWe performed a territory-wide retrospective cohort study involving patients in Hong Kong from 2012 to 2020. Patients who received an oral anticoagulant and had undergone colonoscopy with polypectomy were identified. Propensity-score models with inverse probability of treatment weighting were developed for the warfarin-DOAC and between-DOAC comparisons. The primary outcome was clinically significant delayed PPB, defined as repeat colonoscopy requiring haemostasis within 30 days. The secondary outcomes were 30-day blood transfusion requirement and new thromboembolic event.ResultsApixaban was associated with lower PPB risk than warfarin (adjusted HR (aHR) 0.39, 95% CI 0.24 to 0.63, p<0.001). Dabigatran (aHR 2.23, 95% CI 1.04 to 4.77, adjusted p (ap)=0.035) and rivaroxaban (aHR 2.72, 95% CI 1.35 to 5.48, ap=0.002) were associated with higher PPB risk than apixaban. In subgroup analysis, apixaban was associated with lower PPB risk in patients aged ≥70 years and patients with right-sided colonic polyps.For thromboembolic events, apixaban was associated with lower risk than warfarin (aHR 0.22, 95% CI 0.11 to 0.45, p<0.001). Dabigatran (aHR 2.60, 95% CI 1.06 to 6.41, ap=0.033) and rivaroxaban (aHR 2.96, 95% CI 1.19 to 7.37, ap =0.013) were associated with higher thromboembolic risk than apixaban.ConclusionsApixaban was associated with a significantly lower risk of PPB and thromboembolism than warfarin, dabigatran and rivaroxaban, particularly in older patients with right-sided polyps.