Coronavirus disease 2019 (COVID-19) most commonly presents with respiratory symptoms, including cough, shortness of breath, and sore throat. However, digestive symptoms also occur in patients with COVID-19 and are often described in outpatients with less severe disease. In this study, we sought to describe the clinical characteristics of COVID-19 patients with digestive symptoms and mild disease severity. METHODS:We identified COVID-19 patients with mild disease and one or more digestive symptoms (diarrhea, nausea, and vomiting), with or without respiratory symptoms, and compared them with a group presenting solely with respiratory symptoms. We followed up patients clinically until they tested negative for COVID-19 on at least 2 sequential respiratory tract specimens collected ‡24 hours apart. We then compared the clinical features between those with digestive symptoms and those with respiratory symptoms. RESULTS:There were 206 patients with low severity COVID-19, including 48 presenting with a digestive symptom alone, 69 with both digestive and respiratory symptoms, and 89 with respiratory symptoms alone. Between the 2 groups with digestive symptoms, 67 presented with diarrhea, of whom 19.4% experienced diarrhea as the first symptom in their illness course. The diarrhea lasted from 1 to 14 days, with an average duration of 5.4 6 3.1 days and a frequency of 4.3 6 2.2 bowel movements per day. Concurrent fever was found in 62.4% of patients with a digestive symptom. Patients with digestive symptoms presented for care later than those with respiratory symptoms (16.0 6 7.7 vs 11.6 6 5.1 days, P < 0.001). Nevertheless, patients with digestive symptoms had a longer duration between symptom onset and viral clearance (P < 0.001) and were more likely to be fecal virus positive (73.3% vs 14.3%, P 5 0.033) than those with respiratory symptoms. DISCUSSION:We describe a unique subgroup of COVID-19 patients with mild disease severity marked by the presence of digestive symptoms. These patients are more likely to test positive for viral RNA in stool, to have a longer delay before viral clearance, and to experience delayed diagnosis compared with patients with only respiratory symptoms.

Background and Aim Dynamic changes of immunocyte subsets and inflammatory profiles in coronavirus disease 2019 (COVID‐19) patients with gastrointestinal symptoms were undetermined. Methods A single‐center retrospective analysis of 409 severe, hospitalized COVID‐19 patients from 20 January to 29 February 2020 was performed. The longitudinal characteristics of immune inflammatory cytokines in patients with/without diarrhea were analyzed. The relations of diarrhea and immuno‐inflammatory factors with illness course and clinical outcomes were further explored. Results Diarrhea was more common and more serious with longer duration (4.9 ± 1.5 vs 4.2 ± 1.5 days, P = 0.039) and higher frequency (5.5 ± 2.1 vs 4.0 ± 2.0 times/day, P = 0.001) in deceased patients than in the survivors. Also, diarrhea patients were more inclined to develop multi‐organ damage: survivors have longer illness course (media 41.0 vs 36.0 days, P = 0.052) and hospital stays (media 27.0 vs 23.0 days, P = 0.041), and the deceased patients had higher mortality (33.0% vs 22.6%, P = 0.045) and earlier death (media 20.0 vs 25.0 days, P = 0.038). Progressively, neutrophilia and lymphopenia, especially the declined CD8+ T cells, were demonstrated in diarrhea patients relative to the non‐diarrhea cases. The inflammatory cytokines including IL‐6, IL‐10, and TNF‐α were intensively increased in patients with diarrhea. The multivariable logistic analysis showed longer duration of diarrhea (P = 0.036), higher neutrophil counts (P = 0.011), and lower lymphocyte counts (P < 0.001) were independent risk factors of in‐hospital death. The proportional hazards model indicated that longer duration of diarrhea (P = 0.002), higher frequency of diarrhea (P = 0.058), higher neutrophil counts (P = 0.001), lower lymphocyte counts (P = 0.035), and decreased proportion of CD8+ T cells (P < 0.001) were independently associated with longer illness course of the survivors. Conclusions Diarrhea patients were more likely to present with neutrophilia, lymphopenia, and cytokine storm and to develop multi‐organ damage. The inflammatory patterns were independent factors associated with illness course of the survivors and in‐hospital death of severe COVID‐19.

Background and aims Previous study disclosed Fucosyltransferase 2 (Fut2) gene as a IBD risk locus. This study aimed to explore the mechanism of Fut2 in IBD susceptibility and to propose a new strategy for the treatment of IBD. Methods Intestinal epithelium-specific Fut2 knockout (Fut2△IEC) mice was used. Colitis was induced by dextran sulfate sodium (DSS). The composition and diversity of gut microbiota were assessed via 16S rRNA analysis and the metabolomic findings was obtained from mice feces via metabolite profiling. The fecal microbiota transplantation (FMT) experiment was performed to confirm the association of gut microbiota and LPC. WT mice were treated with Lysophosphatidylcholine (LPC) to verify its impact on colitis. Results The expression of Fut2 and α-1,2-fucosylation in colonic tissues were decreased in patients with UC (UC vs. control, P = 0.036) and CD (CD vs. control, P = 0.031). When treated with DSS, in comparison to WT mice, more severe intestinal inflammation and destructive barrier functions in Fut2△IEC mice was noted. Lower gut microbiota diversity was observed in Fut2△IEC mice compared with WT mice (p < 0.001). When exposed to DSS, gut bacterial diversity and composition altered obviously in Fut2△IEC mice and the fecal concentration of LPC was increased. FMT experiment revealed that mice received the fecal microbiota from Fut2△IEC mice exhibited more severe colitis and higher fecal LPC concentration. Correlation analysis showed that the concentration of LPC was positively correlated with four bacteria—Escherichia, Bilophila, Enterorhabdus and Gordonibacter. Furthermore, LPC was proved to promote the release of pro-inflammatory cytokines and damage epithelial barrier in vitro and in vivo. Conclusion Fut2 and α-1,2-fucosylation in colon were decreased not only in CD but also in UC patients. Gut microbiota in Fut2△IEC mice is altered structurally and functionally, promoting generation of LPC which was proved to promote inflammation and damage epithelial barrier.

Autophagy plays a dual role in the responses to the gut microflora. The present study aimed to examine the effects of Lactobacillus rhamnosus ( L. rhamnosus ) on Fusobacterium nucleatum ( F. nucleatum )-induced intestinal dysfunction and to elucidate the underlying mechanisms, with particular focus on autophagy. Inflammatory models were established by treatment with L. rhamnosus following F. nucleatum intervention using cells or a mouse model of dextran sulfate sodium (DSS)-induced acute colitis. Autophagosomes were visualized by confocal microscopy following transfection with a tandem GFP-mCherry-LC3 construct and also by transmission electron microscopy. Autophagy-associated protein levels were examined by western blot analysis and immunohistochemistry. It was observed that F. nucleatum induced the production of pro-inflammatory cytokines in Caco-2 cells and aggravated DSS-induced acute colitis. The autophagic flux was impaired following infection with F. nucleatum . L. rhamnosus treatment attenuated the inflammation induced by F. nucleatum infection and effectively recovered the impaired autophagic flux. In addition, the production of pro-inflammatory cytokines induced by F. nucleatum was enhanced with autophagy inhibitors or the RNA interference of autophagy-related gene 16 like 1 (Atg16L1) in Caco-2 cells. Notably, this inhibition of autophagy weakened the effects of L. rhamnosus . Finally, the PI3K/AKT/mTOR pathway was found to be involved in this process. On the whole, the present study demonstrates that the mediation of autophagy by L. rhamnosus may be involved in the protective effects against F. nucleatum -related intestinal inflammation. Thus, L. rhamnosus treatment may prove to be a novel therapeutic strategy for F. nucleatum -realated gut disorders.

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The recovery of the intestinal epithelial barrier is the goal for curing various intestinal injurious diseases, especially IBD. However, there are limited therapeutics for restoring intestinal epithelial barrier function in IBD. The stemness of intestinal stem cells (ISCs) can differentiate into various mature intestinal epithelial cells, thus playing a key role in the rapid regeneration of the intestinal epithelium. IL-22 secreted by CD4+ T cells and ILC3 cells was reported to maintain the stemness of ISCs. Our previous study found that L-fucose significantly ameliorated DSS-induced colonic inflammation and intestinal epithelial injury. In this study, we discovered enhanced ISC regeneration and increased intestinal IL-22 secretion and its related transcription factor AHR in colitis mice after L-fucose treatment. Further studies showed that L-fucose promoted IL-22 release from CD4+T cells and intestinal lamina propria monocytes (LPMCs) via activation of nuclear AHR. The coculture system of LPMCs and intestinal organoids demonstrated that L-fucose stimulated the proliferation of ISCs through an indirect manner of IL-22 from LPMCs via the IL-22R-p-STAT3 pathway, and restored TNF-α-induced organoid damage via IL-22-IL-22R signaling. These results revealed that L-fucose helped to heal the epithelial barrier by accelerating ISC proliferation, probably through the AHR/IL-22 pathway of LPMCs, which provides a novel therapy for IBD in the clinic.

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Aim. The outbreak of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic, with the main manifestations being of respiratory nature, including pneumonia. It is noteworthy that digestive symptoms are also observed in COVID-19 patients. In this article, we describe the immuno-inflammatory characteristics of low severity COVID-19 patients with digestive symptoms. Methods. Patients with mild symptoms of COVID-19 were split into three groups based on the patients’ symptoms. The first group displayed digestive symptoms only, the second group displayed respiratory symptoms only, and the last group displayed both digestive and respiratory symptoms. Patients were discharged based on negative results of rRT-PCR testing for SARS-CoV-2 from at least two sequential respiratory tract specimens collected ≥24 hours apart. Multiorgan function and immuno-inflammatory characteristics were analyzed for all of the three groups. Results. Mild liver damage and activation of the immuno-inflammatory system were the most common abnormalities observed in patients with mild COVID-19 symptoms but no significant differences were found (P>0.05). Patients with digestive symptoms were more likely to have slightly higher and later peak values of inflammatory cytokines during the subsequent course of disease (P<0.05). In addition, a significant correlation between IL-2 and TNF level was found in the first group which included patients with digestive symptoms only (P<0.05). Conclusions. Patients with mild cases of COVID-19 only displaying digestive symptoms are a special subtype. Patients in this group were more likely to have slightly higher and delayed peak values of inflammatory cytokines during the subsequent course of the disease. Prevention and clinical management of this type should be taken into consideration.