Linking the gut microbiota to persistent symptoms in survivors of COVID-19 after discharge

Zhou Yaya,Zhang Jianchu,Zhang Dongmei,Ma Wan-Li,Wang Xiaorong 한국미생물학회 2021 The journal of microbiology Vol.59 No.10

Several follow-up studies have found that COVID-19 (coronavirus disease 2019) patients had persistent symptoms after discharge. Gut microbiota play an important role in human health and immune responses. Therefore, this study investigated the gut microbiota of recovered COVID-19 patients and the correlations between gut microbiota and persistent symptoms after discharge. Stool samples were collected from 15 recovered healthcare workers (HCWs) with COVID-19 at three months after discharge, in addition, stool samples were collected from 14 healthy controls (HCs) to perform 16S rRNA gene sequencing between May and July 2020. Compared with HCs, recovered HCWs had reduced bacterial diversity at three months after discharge, with a significantly higher relative abundance of opportunistic pathogens, and a significantly lower relative abundance of beneficial bacteria. In addition, Escherichia unclassified was positively correlated with persistent symptoms at three months after discharge, including fatigue (r = 0.567, p = 0.028), chest tightness after activity (r = 0.687, p = 0.005), and myalgia (r = 0.523, p = 0.045). Intestinibacter bartlettii was positively correlated with anorexia (r = 0.629, p = 0.012) and fatigue (r = 0.545, p = 0.036). However, Faecalibacterium prausnitzii was negatively correlated with chest tightness after activity (r = -0.591, p = 0.02), and Intestinimonas butyriciproducens was negatively correlated with cough (r = -0.635, p = 0.011). In conclusion, the gut microbiota of recovered HCWs with COVID-19 at three months after discharge was different from that of HCs, and altered gut microbiota was correlated with persistent symptoms after discharge, highlighting that gut microbiota may play an important role in the recovery of patients with COVID-19.

Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge

Zhang Dongmei,Zhou Yaya,Ma Yanling,Chen Ping,Tang Jian,Yang Bohan,Li Hui,Liang Mengyuan,Xue YuE,Liu Yao,Zhang Jianchu,Wang Xiaorong 대한의학회 2023 Journal of Korean medical science Vol.38 No.15

Background: Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. Methods: We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. Results: In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing. Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. Conclusion: This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.

Mesenchymal Stem Cell-Derived Exosomes are Effective for Radiation Enteritis and Essential for the Proliferation and Differentiation of Lgr5+ Intestinal Epithelial Stem Cells by Regulating Mir-195/Akt/β-Catenin Pathway

Yang Leilei,Fang Chengfeng,Song Caifang,Zhang Yaya,Zhang Ruili,Zhou Shenkang 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.5

BACKGROUND: Radiation enteritis (RE) is a common complication of abdominal or pelvic radiotherapy, which when severe, could be life-threatening. Currently, there are no effective treatments. Studies have shown that mesenchymal stem cells (MSCs)-derived exosomes (MSC-exos) exhibit promising therapeutic effects in inflammatory diseases. However, the specific role of MSC-exos in RE and the regulatory mechanisms remain elusive. METHODS: In vivo assay was carried out by injecting MSC-exos into the total abdominal irradiation (TAI)-induced RE mouse model. For in vitro assay, Lgr5-positive intestinal epithelial stem cells (Lgr5? IESC) were extracted from mice, followed by irradiation along with MSC-exos treatment. HE staining was performed to measure histopathological changes. mRNA expression of inflammatory factors TNF-a and IL-6 and stem cell markers LGR5, and OCT4 were quantified by RT-qPCR. EdU and TUNEL staining was performed to estimate cell proliferation and apoptosis. MiR-195 expression in TAI mice and radiation-induced Lgr5? IESC was tested. RESULTS: We found that the injection of MSC-exos inhibited inflammatory reaction, increased stem cell marker expression, and maintained intestinal epithelial integrity in TAI mice. Furthermore, MSC-exos treatment increased the proliferation and simultaneously suppressed apoptosis in radiation-stimulated Lgr5? IESC. MiR-195 expression increased by radiation exposure was decreased by MSC-exos therapy. MiR-195 overexpression facilitated the progress of RE by counteracting the effect of MSC-exos. Mechanistically, the Akt and Wnt/b-catenin pathways inhibited by MSC-exos were activated by miR-195 upregulation. CONCLUSION: MSC-Exos are effective in treating RE and are essential for the proliferation and differentiation of Lgr5? IESCs. Moreover, MSC-exos mediates its function by regulating miR-195 Akt b-catenin pathways.

Three-Month Follow-Up Study of Survivors of Coronavirus Disease 2019 after Discharge

Liang Limei,Yang Bohan,Jiang Nanchuan,Fu Wei,He Xinliang,Zhou Yaya,Ma Wan-Li,Wang Xiaorong 대한의학회 2020 Journal of Korean medical science Vol.35 No.47

Background: Most patients including health care workers (HCWs) survived the coronavirus disease 2019 (COVID-19), however, knowledge about the sequelae of COVID-19 after discharge remains limited. Methods: A prospectively observational 3-month follow-up study evaluated symptoms, dynamic changes of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) IgG and IgM, lung function, and high resolution computed tomography (HRCT) of survivors of COVID-19 after discharge at Wuhan Union Hospital, China. Results: Seventy-six survivors (55 females) with a mean age of 41.3 ± 13.8 years were enrolled, and 65 (86%) were HCWs. A total of 69 (91%) patients had returned to their original work at 3-months after discharge. Most of the survivors had symptoms including fever, sputum production, fatigue, diarrhea, dyspnea, cough, chest tightness on exertion and palpitations in the three months after discharge. The serum troponin-I levels during the acute illness showed high correlation with the symptom of fatigue after hospital discharge (r = 0.782; P = 0.008) and lymphopenia was correlated with the symptoms of chest tightness and palpitations on exertion of patients after hospital discharge (r = −0.285, P = 0.027; r = −0.363, P = 0.004, respectively). The mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, total lung capacity and diffusion capacity were all normal (> 80% predicted) and lung HRCTs returned to normal in most of the patients (82%), however, 42% of survivors had mild pulmonary function abnormalities at 3-months after discharge. SARS-CoV-2 IgG turned negative in 11% (6 of 57 patients), 8% (4 of 52 patients) and 13% (7 of 55 patients), and SARS-CoV-2 IgM turned negative in 72% (41 of 57 patients), 85% (44 of 52 patients) and 87% (48 of 55 patients) at 1-month, 2-months and 3-months after discharge, respectively. Conclusion: Infection by SARS-CoV-2 caused some mild impairments of survivors within the first three months of their discharge and the duration of SARS-CoV-2 antibody was limited, which indicates the necessity of long-term follow-up of survivors of COVID-19.