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Background At present, ursodeoxycholic acid (UDCA) is internationally recognized as a therapeutic drug in clinic. However, about 40% Primary Biliary Cholangitis (PBC) patients are poor responders to UDCA. It has been demonstrated that Transcutaneous Neuromodulation (TN) can be involved in gut motility, metabolism of bile acids, immune inflammation, and autonomic nerve. Therefore, this study aimed to explore the effect of TN combined with UDCA on PBC and related mechanisms. Methods According to inclusion and exclusion criteria, 10 healthy volunteers and 15 PBC patients were recruited to control group and TN group, respectively. PBC patients were alternately but blindly assigned to group A (TN combined with UDCA) and group B (sham-TN combined with UDCA), and a crossover design was used. The TN treatment was performed via the posterior tibial nerve and acupoint ST36 (Zusanli) 1 h twice/day for 2 weeks. T test and nonparametric test were used to analyze the data. Results 1. TN combined with UDCA improved the liver function of PBC patients shown by a significant decrease of alkaline phosphatase and gamma-glutamyltransferase (γ-GT) (P P Conclusions TN cssombined with UDCA can significantly improve the liver function of PBC patients. It is possibly via the cholinergic anti-inflammatory pathway. TN might be a new non-drug therapy for PBC. Further studies are required. Trial registration The study protocol was registered in Chinese Clinical Trial Registry (number ChiCTR1800014633) on 25 January 2018.

Background: Gut ecosystem has profound effects on host physiology and health. Gastrointestinal (GI) symptoms were frequently observed in patients with COVID-19. Compared with other organs, gut antiviral response can result in more complicated immune responses because of the interactions between the gut microbiota and host immunity. However, there are still large knowledge gaps in the impact of COVID-19 on gut molecular profiles and commensal microbiome, hindering our comprehensive understanding of the pathogenesis of SARS-CoV-2 and the treatment of COVID-19.Results: We performed longitudinal stool multi-omics profiling to systemically investigate the molecular phenomics alterations of gut ecosystem in COVID-19. Gut proteomes of COVID-19 were characterized by disturbed immune, proteolysis and redox homeostasis. The expression and glycosylation of proteins involved in neutrophil degranulation and migration were suppressed, while those of proteases were upregulated. The variable domains of Ig heavy chains were downregulated and the overall glycosylation of IgA heavy chain constant regions, IgGFc-binding protein, and J chain were suppressed with glycan-specific variations. There was a reduction of beneficial gut bacteria and an enrichment of bacteria derived deleterious metabolites potentially associated with multiple types of diseases (such as ethyl glucuronide). The reduction of Ig heave chain variable domains may contribute to the increase of some Bacteroidetes species. Many bacteria ceramide lipids with a C17-sphingoid based were downregulated in COVID-19. In many cases, the gut phenome did not restore two months after symptom onset.Conclusions: Our study indicates widely disturbed gut molecular profiles which may play a role in the development of symptoms in COVID-19. Our findings also emphasis the need for ongoing investigation of the long-term gut molecular and microbial alterations during COVID-19 recovery process. Considering the gut ecosystem as a potential target could offer a valuable approach in managing the disease.

ObjectiveTo study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients.DesignWe analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues.ResultsAmong the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients.ConclusionsGI tract may be a potential transmission route and target organ of SARS-CoV-2.

This study aims to investigate the role of transcutaneous neuromodulation (TN) on the regulation of gastrointestinal hormones and bile acids in patients with functional constipation (FC). Twenty FC patients were treated with TN for four weeks. The effects of TN on symptoms were evaluated by questionnaires. Plasma levels of serotonin (5-HT), motilin, somatostatin, and vasoactive intestinal peptide (VIP) were measured by ELISA and 12 individual bile acids assayed by liquid chromatography tandem mass spectrometry. Results were as follows. (1) TN treatment increased the frequency of spontaneous bowel movement, improved the Bristol Stool Score, and reduced Patient Assessment of Constipation Symptom score and Patient Assessment of Constipation Quality of Life score. (2) FC patients showed decreased plasma levels of 5-HT, motilin, and VIP and an increased plasma level of somatostatin (P<0.05). Four-week TN treatment increased plasma levels of 5-HT and motilin and decreased the plasma level of somatostatin in the FC patients (P<0.05). (3) Taurocholic deoxycholate, taurocholic acid, and taurocholic lithocholic acid were increased in the FC patients (P<0.005) but reduced by TN treatment (P<0.05). This study has suggested that the therapy may improve the symptoms of FC by alleviating the disorders of gastrointestinal hormones and bile acids.

Gut ecosystem has profound effects on host physiology and health. Gastrointestinal (GI) symptoms were frequently observed in patients with COVID-19. Compared with other organs, gut antiviral response can result in more complicated immune responses because of the interactions between the gut microbiota and host immunity. However, there are still large knowledge gaps in the impact of COVID-19 on gut molecular profiles and commensal microbiome, hindering our comprehensive understanding of the pathogenesis of SARS-CoV-2 and the treatment of COVID-19. We performed longitudinal stool multi-omics profiling to systemically investigate the molecular phenomics alterations of gut ecosystem in COVID-19. Gut proteomes of COVID-19 were characterized by disturbed immune, proteolysis and redox homeostasis. The expression and glycosylation of proteins involved in neutrophil degranulation and migration were suppressed, while those of proteases were upregulated. The variable domains of Ig heavy chains were downregulated and the overall glycosylation of IgA heavy chain constant regions, IgGFc-binding protein, and J chain were suppressed with glycan-specific variations. There was a reduction of beneficial gut bacteria and an enrichment of bacteria derived deleterious metabolites potentially associated with multiple types of diseases (such as ethyl glucuronide). The reduction of Ig heave chain variable domains may contribute to the increase of some Bacteroidetes species. Many bacteria ceramide lipids with a C17-sphingoid based were downregulated in COVID-19. In many cases, the gut phenome did not restore two months after symptom onset. Our study indicates widely disturbed gut molecular profiles which may play a role in the development of symptoms in COVID-19. Our findings also emphasis the need for ongoing investigation of the long-term gut molecular and microbial alterations during COVID-19 recovery process. Considering the gut ecosystem as a potential target could offer a valuable approach in managing the disease., Graphical abstract Image 1