Centre For Digestive Diseases

BackgroundAntitumor drugs (such as chemotherapy, targeted therapy, immunotherapy, etc.) and local treatments like surgery and radiotherapy are widely used in cancer treatment, but they often carry the risk of liver injury, which seriously affects the prognosis and quality of life of patients. Therefore, liver protection is of crucial importance in cancer treatment.MethodsRelevant experts organized by the Oncology Hepatology Committee of China Anti-Cancer Association Association formulated this guideline based on the latest research achievements and clinical practice experience at home and abroad, aiming to provide comprehensive and systematic guidance for clinicians on liver protection.ResultsThis guideline elaborates on the importance of liver protection during cancer treatment, comprehensively introduces the pathophysiological mechanisms, diagnosis, treatment, and preventive measures of antitumor treatment-related liver injury.ConclusionThis guideline is helpful for clinicians to formulate individualized treatment plans, improve the treatment outcome and quality of life of cancer patients, and provides an important reference for the clinical practice of liver protection in cancer treatment.

Introduction: Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) syndrome is a condition that impairs normal neurological brain function and is triggered by a streptococcal infection. It is characterised by an obsessive-compulsive disorder (OCD) tic disorder, or both and usually occurs suddenly between the age of 3-12 years. Other symptoms include mood changes, anxiety, attention deficit/hyperactivity disorder, trouble sleeping, and joint pain. Metagenomic profiles of those with PANDAS syndrome show an altered gut bacterial community. Commonly treatment involves antibiotics for streptococcal infection. Here, we report on the effects of fecal microbiota transplantation (FMT) on a set of identical twins with concomitant PANDAS syndrome. Case Description/Methods: Case 1: A male (16yrs) presented with slow transit type constipation with a colonic transit half clearance time of 70minutes. His medical history also showed he had PANDAS syndrome and later tested positive for Clostridium Difficile (C. difficile). The patient was treated with metronidazole before receiving a single dose of FMT which was transfused colonoscopically. At 1-month the patient tested negative for C. difficile. Post treatment he reported significant improvement in abdominal pain, bloating and constipation that lasted 2 years. Simultaneously he reported symptom improvement in anxiety, depression, and Rheumatoid Arthritis which are associated with PANDAS syndrome. Case 2: A male (16yrs) presented with severe constipation with a normal colonic transit half clearance time of 50minutes. Constipation prompted a worsening of symptoms of concomitant PANDAS syndrome which had previously been treated with steroids. After further testing he was found to have C. difficile for which he was prescribed metronidazole and vancomycin before receiving a single dose of FMT by colonoscopic infusion. At 1-month post treatment eradication of C. difficile was confirmed. Post treatment he reported experiencing improvement in constipation, diarrhoea, flatulence, and vomiting which lasted for 2 years. He also reported symptom improvement in Autism, OCD, and Rheumatoid Arthritis which are linked to PANDAS syndrome. Discussion: To the best of our knowledge these are the first cases of improvement in PANDAS symptoms after FMT treatment. Further study is required into the effects of FMT on PANDAS syndrome before FMT can be confirmed as a potential treatment.

Introduction: Messenger RNA vaccines for preventing SARS-CoV-2 infection are widely used yet their effect on the gut microbiome is not known. Low bifidobacteria levels have been linked with severe SARS-CoV-2 infection, inflammatory bowel disease, Clostridioides diffícile infection, obesity and aging. Preliminary case reports suggest fecal microbiota transplant could cure SARS-CoV-2 infection (1). A study by Bozkurt et al. showed that SARS-CoV-2 patients taking bifidiobacteria-containing probiotics had lower COVID-related hospitalization times (2). Methods: 34 subjects had stool collection prior to vaccination and one month post vaccination to evaluate the relative abundance of bifidobacteria in the gut. DNA was extracted, library was prepped, and enrichment and sequencing were done using metagenomic next generation sequencing. Results: Relative abundance of genus bifidobacteria significantly decreased to about half of original value after vaccination (P = 0.0065 via Wilcoxon signed rank test). Prior to vaccination, median (interquartile range) values of relative abundance for genus bifidobacteria were 1.13% (0.0016% to 2.52%) and after vaccination were 0.64% (0.0015% to 2.48%). Conclusion: Bifidobacteria, included in the $1 billion industry of probiotics, has been shown to be critical in inflammatory diseases, severe COVID-19, obesity, and the aging process. Our results, although preliminary suggest that SARS COV-2 mRNA vaccine decreases levels of bifidobacteria (P = 0.0065). Future studies will be needed to characterize the time course of this decrease in bifidobacteria abundance, its impact on human health, and whether or not similar findings are seen with other vaccines (Figure).Figure 1.: Bifidobacterium relative abundance decreases ( P = 0.0065) in subjects (n=34) after vaccination compared to before vaccination in the same subjects. Bars plot median; error bars plot interquartile range

Introduction: Ankylosing spondylitis (AS) is an autoimmune disease which causes inflammatory arthritis in the spine and sacroiliac joints. Symptoms of AS include back pain, stiffness and reduced mobility in the spine. Patients with AS are known to have subclinical gut wall inflammation and dysbiosis in the gut. There is no known treatment to cure AS. Here, we report incidental improvement in AS in 2 patients with irritable bowel syndrome predominant diarrhoea (IBS-D) who received faecal microbiota transplant (FMT). Case Description/Methods: Case one: Female, 47 years of age, with known IBS-D, presented with recurrent abdominal pain, explosive diarrhoea 5 time a day, nocturnal bowel motions and urgency. At the same time, she was on salazopyrin and arava for her AS with limited improvement in symptoms. Stool testing was for positive Clostridium difficile toxin and she received 2 fresh FMT’s (one via colonoscopy, one via enema) in 2016. Testing 1 month after FMT treatment was negative to Clostridium difficile toxin. The patient had no ongoing gastrointestinal (GI) symptoms. She also reported significant improvement in AS symptoms (specifically reduction in excruciating pain in lower back and hip). After 5 years, her IBS-D symptoms relapsed and she had another 2 FMTs (one via colonoscopy, one via enema) which resulted in improvements in GI symptoms and more improvement in AS than previous FMTs. Her CRP and ESR levels were normal pre and post treatment. Case 2: Male, 68 years of age, with known IBS-D received fresh 2 FMTs (one via colonoscopy, one via enema) in 2005 for treatment of IBS-D. Prior to treatment he had abdominal pain, cramps and loose motion and AS symptoms including excruciating pain in the sacroiliac joint. He was on infliximab and analgesics for his AS. After FMT treatment, he reported resolution of all GI symptoms and AS symptoms. His pre and post CRP levels were 100 and 2.6 and ESR levels were 18 and 7 respectively. In 2009, he had antibiotic treatment for sinusitis and his GI symptoms relapsed. He had a further 5 FMTs, again with complete recovery of GI symptoms and continued AS remission. Discussion: We observed short-term and long-term improvement in AS symptoms after treating patients with FMT. Future prospective trials are required to confirm FMT as a treatment for AS.

Fecal microbiota transplantation (FMT) has been used as a core therapy for treating dysbiosis-related diseases by remodeling gut microbiota. The methodology and technology for improving FMT are stepping forward, mainly including washed microbiota transplantation (WMT), colonic transendoscopic enteral tubing (TET) for microbiota delivery, and purified Firmicutes spores from fecal matter. To improve the understanding of the clinical applications of FMT, we performed a systematic literature review on FMT published from 2011 to 2021. Here, we provided an overview of the reported clinical benefits of FMT, the methodology of processing FMT, the strategy of using FMT, and the regulations on FMT from a global perspective. A total of 782 studies were included for the final analysis. The present review profiled the effectiveness from all clinical FMT uses in 85 specific diseases as eight categories, including infections, gut diseases, microbiota–gut–liver axis, microbiota–gut–brain axis, metabolic diseases, oncology, hematological diseases, and other diseases. Although many further controlled trials will be needed, the dramatic increasing reports have shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut.

Introduction: Microbiome diversity is a surrogate marker for microbiome health with decreased diversity observed in many diseases. Key to disease pathogenesis in recurrent Clostridioides difficile infection (CDI) is decreased microbiome diversity and impaired colonization resistance. CP101 is an investigational orally administered microbiome therapeutic designed to restore microbiome diversity and enable early intervention in the management of recurrent CDI. Microbiome diversity is a key pharmacodynamic marker in recurrent CDI; however, data on the impact of increasing diversity on efficacy is scarce. Methods: We conducted a double-blind, randomized, placebo-controlled trial (PRISM3) enrolling adults who received standard-of-care antibiotics for recurrent CDI. Patients with first CDI recurrence at high-risk for further recurrence (≥65 years), or those with two or more recurrences were eligible. The qualifying CDI episode was diagnosed prior to study entry by guideline recommended testing (PCR-based or toxin EIA-based). Following CDI antibiotics, participants completed a minimum 2-day washout period. Eligible participants were randomized 1:1 to receive one-time oral administration of CP101 or placebo without bowel preparation. The primary efficacy endpoint was sustained clinical cure, defined as an absence of CDI recurrence through Week 8 following dosing. Diversity of the intestinal microbiome was measured at baseline, Week 1, and Week 8 using 16S rRNA gene amplicon sequencing. Results: Among the 198 enrolled participants analyzed, the CP101 arm demonstrated a statistically significant and clinically meaningful improvement in sustained clinical cure compared to placebo through Week 8 (74.5% [76/102] vs 61.5% [59/96], P=0.0488). Alpha diversity was low in the CP101 and placebo arms at baseline, and similar between both groups. Participants treated with CP101 achieved significantly higher alpha diversity compared to placebo, and the increase in diversity was rapid and sustained over time (p< 0.001 at Week 1, p< 0.0001 at Week 8) (Fig. 1a). Participants who received CP101 also had a significantly greater change in their microbial community composition from baseline compared to placebo at Week 1 (p< 0.001). Clinically, an increase in microbiome diversity at Week 1 was associated with sustained clinical cure through Week 8 (p< 0.001) (Fig. 1b). Conclusion: These data suggest that CP101 restores microbiome diversity, leading to colonization resistance and driving sustained clinical cure in recurrent CDI.Figure 1.: a. CP101 drives restoration of microbiome diversity. B. An increase in microbiome diversity at Week 1 is associated with sustained clinical cure through Week 8.

INTRODUCTION: Constipation-predominant irritable bowel syndrome (IBS-C) is characterised by symptoms of infrequent and/or difficult to pass stools. IBS-C can also be associated with abdominal pain, bloating, flatulence and fatigue. Due to lack of effective treatments, it is important to investigate promising alternative therapies in order to normalise bowel frequency, and reduce other symptoms. We had previously noticed that using combined antibiotics for H pylori often eased IBS-C, and that vancomycin can improve defecation1, 2. This study aimed to investigate the efficacy of personalised combination antibiotic treatments for IBS-C and evaluate the patients’ clinical outcomes. METHODS: This retrospective, single centred study included patients 16 years or older, diagnosed with IBS-C (and no other underlying disease) who attended our Clinic for treatment between June 2017 and June 2018. Patients treated with combination rifaximin and vancomycin with or without any other medications were included in the study. Demographics and symptoms including bowel frequency data at baseline and 8-weeks on-treatment were recorded. Wilcoxon signed rank test was used to compare the differences pre and on-treatment. P values of < 0.05 were considered significant. RESULTS: A total of 57 patients (M 16, median age 43) diagnosed with IBS-C were included in the study. In addition to infrequent bowel motions, the most common symptoms experienced by this cohort were bloating (65%) and abdominal pain (49%). Patients undertook 7 personalised treatment combinations which all included rifaximin and vancomycin with or without other medications (Table 1). Out of the 57 patients treated for IBS-C, 46 (81%) had a follow-up available at 8 weeks on-treatment. A significant improvement in the frequency of bowel motions (BM) was observed at 8 weeks on-treatment (median BM = 1/day) compared to the baseline (median BM = 1/3-4days) (P < 0.001). The only side effect reported was mild diarrhoea which was experienced with 3 patients during the antibiotic course. CONCLUSION: This study demonstrates the efficacy of personalised treatment comprising of combination of antibiotics such as rifaximin and vancomycin in the treatment of IBS-C. Importantly, a significant increase in number of bowel motions was observed among patients. Future studies need to investigate the efficacy of these antibiotics in relieving the symptoms of constipation and their effect on the gut microbiome.Table 1.: Treatment combination types