Acupuncture treatment in gastrointestinal diseases: A systematic review

The purpose of this work was to assess the evidence for effectiveness of acupuncture （AC） treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed up to May 2006. Controlled trials assessing acupuncture point stimulation for patients with gastrointestinal diseases were considered for inclusion. The search identified 18 relevant trials meeting the inclusion criteria. Two irritable bowel syndrome （IBS） trials, 1 Crohn＇s disease and 1 colitis ulcerosa trial had a robust random controlled trial （RCT） design. In regard to other gastrointestinal disorders, study quality was poor. In all trials, quality of life （QoL） improved significantly independently from the kind of acupuncture, real or sham. Real AC was significantly superior to sham acupuncture with regard to disease activity scores in the Crohn and Colitis trials. Efficacy of acupuncture related to QoL in IBS may be explained by unspecific effects. This is the same for QoL in inflammatory bowel diseases （IBD）, whereas specific acupuncture effects may be found in clinical scores. Further trials for IBDs and in particular for all other gastrointestinal disorders would be necessary to evaluate the efficacy of acupuncture treatment. However, it must be discussed on what terms patients benefit when this harmless and obviously powerful therapy with regard to QoL is demystified by further placebo controlled trials.

Favorable response to subcutaneous administration of infliximab in rats with experimental colitis

AIM： To investigate the influence of infliximab （Remicade） on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic add （TNBS） in rats. METHODS： Thirty-six Wistar rats were allocated into four groups （three groups of six animals each and a fourth of 12 animals）. Six more healthy animals served as normal controls （Group 5）. Group 1： colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2： colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3： colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4： colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7^th d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha （TNF-α） and malondialdehyde （MDA） were also measured. RESULTS： Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-α in all groups of treated animals as compared with the untreated ones was found （0.47＋0.44, 1.09＋0.86, 0.43＋0.31 vs 18.73＋10.53 respectively）. Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4. CONCLUSION： Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-α and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-α than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/ kg BW.

Rifaximin in the treatment of inflammatory bowel disease

The gut microbiota plays a role in promoting and maintaining inflammation in inflammatory bowel diseases （IBD）, hence the rationale for the use of antibiotics in the treatment of those disorders. Antibiotics, however, may induce untoward effects, especially during longterm therapy. Rifaximin α polymer is an antibacterial agent that is virtually unabsorbed after oral administration and is devoid of systemic side effects. Rifaximin has provided promising results in inducing remission of Crohn＇s disease （up to 69% in open studies and significantly higher rates than placebo in double blind trials） and ulcerative colitis （76% in open studies and significantly higher rates than placebo in controlled studies） and might also have a role in maintaining remission of ulcerative colitis and pouchitis. The potential therapeutic activity of rifaximin in IBD deserves to be further investigated and confirmed in larger, controlled studies. The optimal dosage still needs to be better defined.

Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult-and pediatric-onset inflammatory bowel disease in Italy

AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.

Angioedema associated with Crohn's disease:Response to biologics

A 46-year-old female patient with terminal ileum Crohn’s disease and ankylosing spondylitis presented with recurrent angioedema and urticaria. Investigations ruled out hereditary angioedema, and environmental or food allergen triggers. She was diagnosed with chronic idiopathic urticaria with angioedema, and was treated with a trial of intravenous immunoglobulin immunotherapy, danazol, prednisone and hydroxyzine. Due to ongoing bowel and arthritic complaints, she was started on infliximab infusions and within 2 treatments, she had complete resolution of the angioedema and urticaria, as well as of the bowel and arthritic symptoms. Unfortunately she developed allergic reactions to the infliximab and was switched to another anti-tumor necrosis factor （TNF）-a agent, adalimumab. Since then, she has had no further angioedema or urticaria, and her Crohn’s disease has been quiescent. This is the first known case report of chronic idiopathic urticaria with angioedema coexistent with Crohn’s disease that was successfully treated with anti-TNF-α agents.

Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

Long CoVID,also known for post-acute sequelae of CovID-19,describes the people who have the signs and symptoms that continue or develop after the acute coviD-19 phase.Long CovID patients suffer from an inflammation or host responses towards the virus approx-imately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an unchar-acterized duration.Anyone infected with CovID-19 before could experience long-CcovID conditions,including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection early.People with long CoviD may experience health problems from different types and combinations of symptoms over time,such as fa-tigue,dyspnea,cognitive impairments,and gastrointestinal(Gl)symptoms(e.g.,nausea,vom-iting,diarrhea,decreased or loss of appetite,abdominal pain,and dysgeusia).The critical role of the microbiome in these Gl symptoms and long CovID were reported in clinical patients and experimental models.Here,we provide an overall view of the critical role of the Gl tract and microbiome in the development of long COVID,including the clinical Gl symptoms in patients,dysbiosis,viral-microbiome interactions,barrier function,and inflammatory bowel disease patients with long CovID.We highlight the potential mechanisms and possible treatment based on Gl health and microbiome.Finally,we discuss challenges and future direction in the long CoVID clinic and research.

The journey of gut microbiome - An introduction and its influence on metabolic disorders

BACKGROUND： Metabolic disorders such as Obesity, Diabetes Type 2 （T2DM） and Inflammatory Bowel Diseases （IBD） are the most prevalent globally. Recently, there has been a surge in the evidence indicating the correlation between the intestinal microbiota and development of these metabolic conditions apart from predisposing genetic and epigenetic factors. Gut microbiome is pivotal in controlling the host metabolism and physiology. But imbalances in the microbiota patterns lead to these disorders via several pathways. Animal and human studies so far have concentrated mostly on metagenomics for the whole microbiome characterization to understand how microbiome supports health in general. However, the accurate mechanisms connecting the metabolic disorders and alterations in gut microbial composition in host and the metabolites employed by the microorganisms in regulating the metabolic disorders is still vague. OBJECTIVE： The review delineates the latest findings about the role of gut microbiome to the pathophysiology of Obesity, IBD and Diabetes Mellitus. Here, we provide a brief introduction to the gut microbiome followed by the current therapeutic interventions in restoration of the disrupted intestinal microbiota. METHODS： A methodical PubMed search was performed using keywords like ＂gut microbiome,＂ ＂obesity, diabetes,＂ ＂IBD,＂ and ＂metabolic syndromes.＂ All significant and latest publications up to January 2018 were accounted for the review. RESULTS： Out of the 93 articles cited, 63 articles focused on the gut microbiota association to these disorders. The rest 18 literature outlines the therapeutic approaches in maintaining the gut homeostasis using probiotics, prebiotics and faecal microbial transplant （FMT）. CONCLUSION： Metabolic disorders have intricate etiology and thus a lucid understanding of the complex host-microbiome inter-relationships will open avenues to novel therapeutics for the diagnosis, prevention and treatment of the metabolic diseases.

Microbiota transplantation： concept, methodology and strategy for its modernization

Fecal microbiota transplantation （FMT） has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut- brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step- up FMT strategy based on literature and state experts＇ perspectives.