T cells play a vital role in hepatitis B virus (HBV) infection, mediating both protective immunity and immunopathology. Deep profiling of the T cell receptor (TCR) complementarity-determining region 3 (CDR3) provides critical insights into T cell composition and function. However, the characteristics of the TCR α-chain (TRA) and β-chain (TRB) repertoires in individuals with different HBV infection and vaccination statuses remain incompletely understood. We employed high-throughput sequencing (HTS) to profile the TRA and TRB CDR3 repertoires in peripheral blood mononuclear cells (PBMCs) from 6 inoculation-positive responders (IPR) to hepatitis B (HepB) vaccination, 6 individuals with chronic hepatitis B (CHB), and 5 healthy donors (HD). We systematically compared the frequency, diversity, similarity, and V/J segment usage of TRA and TRB CDR3s across the three groups. The CHB group exhibited significantly fewer unique TRA and TRB CDR3s than both IPR and HD groups. Overlap analysis revealed that the BUB index for TRAV was significantly higher in IPR than in CHB and HD groups (P = 0.0073 and P = 0.0317, respectively), while for TRBV, a significantly higher BUB index was observed only between IPR and CHB groups (P = 0.0002). Additionally, identical TRA CDR3s were preferentially shared among individuals within each group, whereas TRBJ usage remained relatively stable across groups. Collectively, our findings delineate distinct CDR3 repertoire characteristics of circulating T cells in IPR and CHB, which may enhance understanding of the protective response to HepB vaccination and inform future investigations into TRA- and TRB-based strategies for HBV diagnosis and prevention.

Background The intestinal microbiota is an important factor that can influence hepatitis E (HE) susceptibility, pathogenesis, and clinical outcome. However, the microbial signatures associated with HE severity remain poorly defined. Results In this study, we performed shotgun metagenomic profiling to characterize intestinal microbial alterations across patients with acute liver failure (ALF), acute icteric HE (AIH), acute nonicteric HE (ANIH), and healthy individuals. We found that most of the species enriched in the ALF group were from the genera Streptococcus and Veillonella , and most of those enriched in the ANIH group and healthy controls were butyrate producers. Species coabundance analysis revealed that the abundances of Streptococcus -associated species coabundance group 5 (sCAG5) and Veillonella -associated sCAG4 were highest in the ALF group, followed by the AIH group, ANIH group and healthy controls. Pearson correlation analyses revealed that the levels of serum albumin (ALB) and cholinesterase (CHE) were negatively correlated with the ratio of the total abundance of sCAG5 and sCAG4 to the abundance of butyrate producers associated with sCAG10, suggesting that sCAG5, sCAG4, and sCAG10 are likely involved in the severity of HE. Furthermore, the differentially expressed microbial genes in the ALF group versus the healthy control group as well as versus the ANIH group were derived from species in sCAG4 and sCAG5. Conclusion We identified the ratio of total sCAG5 and sCAG4 to sCAG10 as an intestinal microbial indicator of HE severity, providing novel insight into the roles of the intestinal microbiome in HE exacerbation.

Growing evidence suggests a role for the gut microbiome in progression of cholangiocarcinoma (CCA), however, its diagnostic and therapeutic potential remains incompletely characterized. Here, metagenomic sequencing was performed on fecal samples (n = 785) from individuals across East, Central, and Northwestern China. Gut microbial dysbiosis in CCA was characterized by depletion of short-chain fatty acids-producing species and enrichment of potential pathobionts (Klebsiella aerogenes, Clostridium symbiosum). Diagnostic models built using species-level markers demonstrated superior performance, compared to pathway-based models, achieving area under the curve (AUC) values of 98.63% and 99.42% in the discovery cohort, with robust cross-regional validation (AUC = 80.89% and 80.43%). The model effectively distinguished CCA from hepatocellular carcinoma (AUC = 97.86%) and liver fibrosis (AUC = 98.73%) and nonalcoholic fatty liver disease (mean AUC = 96.86%). Analysis of public datasets encompassing 6847 samples across 31 studies and 11 disease states revealed moderate disease specificity influenced by biomarker overlap across conditions. Mechanistically, depleted Bifidobacterium pseudocatenulatum suppressed CCA progression, associated with inhibition of the PI3K-AKT-mTOR pathway. Collectively, this study supports the potential of fecal metagenomic signatures as a complementary noninvasive aid for CCA detection, and provides functional evidence for a candidate protective microbe.

Chemokines, a family of chemotactic cytokines, play a central role in shaping the tumor microenvironment (TME) and in influencing the progression of hepatocellular carcinoma (HCC), a well-known inflammation-related cancer. This review addresses the intricate interplay between chemokines and HCC and highlights their multifaceted role. We discuss how altered expression of chemokines within the TME contributes to the development of HCC by orchestrating the recruitment of immune cells, ultimately leading to immunosuppression. In addition, we are investigating the contribution of chemokines to important features of HCC progression, including angiogenesis and epithelial-mesenchymal transition (EMT). The potential of chemokines as serum biomarkers for HCC diagnosis and their potential as novel therapeutic targets are also explored. This comprehensive review emphasizes the importance of chemokines in the pathogenesis of HCC and their potential for a better understanding and treatment of this difficult disease.

Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.

Objective:To investigate the effect of the Yangyin Yiqi Huoxue formula on the oral microecology in a mouse model of Sjögren's syndrome (SS), and to explore the underlying mechanisms. Methods:A total of 12 8-week-old non-obese diabetic (NOD) mice were randomly assigned to a model group, a traditional Chinese medicine (TCM) group, and a hydroxychloroquine (HCQ) group, with 4 mice in each group. In addition, 4 BALB/c mice were used as the normal control group. The TCM group was administered Yangyin Yiqi Huoxue formula (15 g/[kg·d]) via gavage and the HCQ group received HCQ (0.08 g/[kg·d]) via gavage. The normal control and model groups were maintained under standard feeding conditions without intervention. After 8 weeks of treatment, saliva samples were collected for 16S rRNA gene sequencing to analyze the oral microbiota. Alpha diversity, beta diversity, and functional prediction analyses were performed. Results:Alpha diversity analysis showed that the Yangyin Yiqi Huoxue formula significantly increased oral microbiome diversity in NOD mice (P < 0.05). Species composition analysis indicated that the formula increased the abundance of the phylum Proteobacteria and decreased the abundance of the phylum Firmicutes (P < 0.01), while HCQ led to an abnormal decrease in the abundance of the phylum Firmicutes. Beta diversity analysis revealed distinct microbial clustering in the treatment groups and the model group, with the TCM group showing clustering in the phylum Proteobacteria and exhibiting lower intragroup dispersion than the HCQ group did. According to the functional prediction analysis, both the TCM and HCQ groups demonstrated regulatory potential in terms of amino acid transport and metabolism, transcription, and other related functions. KEGG analysis found greater microbial enrichment in cellular processes, environmental information processing, and disease-related pathways in the TCM group compared to the HCQ group (P < 0.05). Conclusion:The Yangyin Yiqi Huoxue formula can restore oral microbiome diversity and improve the colony structure in in a mouse model of SS, providing experimental evidence for the advantages of TCM in regulating oral microecological functions.

The thyroid-gut axis refers to the intricate relationships among the gut, intestinal microbiota, and thyroid gland, and it is speculated to play an important role in the development of thyroid diseases. The aim of this study was to identify the differentiated bacteria in the intestinal microbiota associated with papillary thyroid carcinoma (PTC) and benign thyroid nodules (BTNs) to offer potential avenues for further exploration and therapeutic interventions. Faecal microbiotas of 197 subjects (73 from subjects with BTNs, 62 from subjects with PTC, and 62 from sex- and age-matched controls) were characterized by sequencing the V3-V4 region of 16 S rDNA using the Illumina NovaSeq 6000 platform. Microbiomics and machine learning-assisted approaches were used to identify the PTC-/BTN-associated intestinal microbial indicators. Compared with the abundance of coabundant groups (CAGs) in the PTC, BTN, and control groups, the abundance of two Genus-CAGs consisting of butyrate producers, such as Blautia, Lachnoclostridium, Lachnospiraceae_unclassified, Eisenbergiella, Flavonifractor and Hungatella, was lower in the PTC group than in the control group. In particular, both ANCOM-BC2 and Wilcoxon rank-sum test results consistently demonstrated significant enrichment of the butyrate-producing genera Oscillibacter, Coprobacter, and Colidextribacter in both BTN patients and healthy controls. The majority of discriminatory amplicon sequence variants (ASVs) that could discriminate PTCs from controls, as well as from BTNs, were from Prevotella, Streptococcus, Bacteroides, and butyrate-producing groups, such as the Oscillibacter, Lachnospiraceae, and Christensenellaceae (R7) groups. ASV indicators from Prevotella and Streptococcus were most abundant in the PTC group, and those from Bacteroides and the butyrate-producing/-promoting group were least abundant in the PTC group. Additionally, the ASVs that could discriminate the BTN group from the control group, as well as PTC group included other butyrate-producing groups, the Clostridium_sensu_stricto group, and the Eubacterium_siraeum group. This study demonstrates that dysbiosis linked to thyroid nodules is marked by a substantial decline in intestinal butyrate-producing and butyrate-promoting taxa. Future work to confirm these results should include shotgun metagenomic sequencing paired with quantitative analyses of gene abundance and expression to fully ascertain the functional implications.

Background:Influenza A virus H1N1 is a significant cause of respiratory infections, leading to severe complications in some patients. Understanding the molecular differences between severe and mild cases can provide insights into the pathogenesis and potential therapeutic targets for H1N1 infections. Objectives:The objectives of the study were to investigate the transcriptional variances in mRNA and lncRNA between severe and mild cases of H1N1 infection to discern potential markers contributing to the severity of the illness. Methods:Transcriptome sequencing was conducted on PBMC samples from 4 severe and 4 mild H1N1-infected patients. The transcriptional profiles of mRNA and lncRNA were analyzed to identify differential expression patterns between the two groups. Results:Analysis revealed 3655 differentially expressed genes (DEGs), including 3147 protein-coding genes and 508 lncRNAs, in severe versus mild H1N1 cases. These genes were linked to essential cellular processes like ribosome assembly and significant signaling pathways such as the MAPK signaling cascade. Conclusion:The identified DEGs, particularly those associated with ribosome assembly and key signaling pathways, may serve as potential biomarkers for distinguishing between severe and mild H1N1 infections. This research sheds light on the distinct transcriptomic features contributing to the pathogenesis of severe H1N1 infections, offering insights into differential diagnosis and potential therapeutic targets.

Hepatic encephalopathy (HE) is a clinical manifestation of neurological and psychiatric abnormalities that are caused by complications of liver dysfunction including hyperammonemia, hyperuricemia, and portal hypertension. Accumulating evidence suggests that HE could be reversed through therapeutic modifications of gut microbiota. Multiple preclinical and clinical studies have indicated that gut microbiome affects the physiological function of the liver, such as the regulation of metabolism, secretion, and immunity, through the gut-liver crosstalk. In addition, gut microbiota also influences the brain through the gut-brain crosstalk, altering its physiological functions including the regulation of the immune, neuroendocrine, and vagal pathways. Thus, key molecules that are involved in the microbiota-gut-liver-brain axis might be able to serve as clinical biomarkers for early diagnosis of HE, and could be effective therapeutic targets for clinical interventions. In this review, we summarize the pathophysiology of HE and further propose approaches modulating the microbiota-gut-liver-brain axis in order to provide a comprehensive understanding of the prevention and potential clinical treatment for HE with a microbiota-targeted therapy.

Nanoplastics (NP) are emerging pollutants in the environment. Bio-based materials are attracting increasing scientific attention as their application may alleviate the environmental pollution caused by conventional plastics. However, their hazardous potentials still need to be investigated. In this study, multi-omics approaches were carried out to explore and compare the conventional polyvinyl chloride (PVC), bio-based polyhydroxyalkanoates (PHA) and water-soluble polyvinyl alcohol (PVA) NP for their lung and liver toxicity in mice. Airborne PVC NP could cause nasal and lung microbial dysbiosis, lung and serum metabolic disruption, liver transcriptomic dysregulation, and result in lung and liver toxicity. In contrast, airborne PHA and PVA NP could induce nasal and lung microbial alterations, lung and serum metabolic disruption, liver transcriptomic disturbance, and lead to mild lung toxicity. As for foodborne PHA, PVA and PVC NP, they all could induce gut microbial dysbiosis, gut and serum metabolic disruption. Foodborne PVC NP could cause similar transcriptomic alterations and greater histological changes in liver compared to PHA NP, while foodborne PVA NP could induce transcriptomic disturbance but not apparent pathology in liver. Among the various alterations, multiple lung pathways (e.g., “renal cell carcinoma”) and liver pathways (e.g., “arachidonic acid metabolism”) were commonly greatly enriched by airborne PHA and PVA NP but not PVC NP, while multiple liver pathways (e.g., “pancreatic secretion”) were commonly largely intensified by foodborne PVC and PHA NP but not PVA NP, aligning with the histological differences between groups. The relevant findings suggest PVA and PHA NP have lower lung and liver toxicity than PVC NP. The results could also benefit the clinical diagnoses of liver and lung toxicity induced by airborne and foodborne PVC, PVA and PHA NP.

Background:Liver cirrhosis is commonly accompanied by intestinal dysbiosis and metabolic defects. Many clinical trials have shown microbiota-targeting strategies represent promising interventions for managing cirrhosis and its complications. However, the influences of the intestinal metagenomes and metabolic profiles of patients have not been fully elucidated.Methods:We administered lactulose, Clostridium butyricum, and Bifidobacterium longum infantis as a synbiotic and used shotgun metagenomics and non-targeted metabolomics to characterize the results.Results:Patients treated with the synbiotic for 12 weeks had lower dysbiosis index (DI) scores than placebo-treated patients and patients at baseline (NIP group). We identified 48 bacterial taxa enriched in the various groups, 66 differentially expressed genes, 18 differentially expressed virulence factor genes, 10 differentially expressed carbohydrate-active enzyme genes, and 173 metabolites present at differing concentrations in the Synbiotic versus Placebo group, and the Synbiotic versus NIP group. And Bifidobacteria species, especially B. longum, showed positive associations with many differentially expressed genes in synbiotic-treated patients. Metabolites pathway enrichment analysis showed that synbiotic significantly affected purine metabolism and aminoacyl-tRNA biosynthesis. And the purine metabolism and aminoacyl-tRNA biosynthesis were no longer significant differences in the Synbiotic group versus the healthy controls group. In conclusion, although littles influence on clinical parameters in the early intervention, the synbiotic showed a potential benefit to patients by ameliorating intestinal dysbiosis and metabolic defects; and the DI of intestinal microbiota is useful for the evaluation of the effect of clinical microbiota-targeting strategies on cirrhotic patients.Clinical Trial Registration:https://www.clinicaltrials.gov, identifiers NCT05687409.

Background It is lacking that markers could predict the prognosis of chronic hepatitis B (CHB) subjects during antiviral treatment, and the related cellular immune mechanism is not fully evaluated. Aim To explore the comprehensive profile of T cell receptor β-chain (TRBV) and CD4+CD25+ regulatory T cell (Treg) in peripheral blood of CHB patients with HBeAg seroconverting (SC) during tenofovir disoproxil fumarate (TDF) treatment. Methods The frequency of CD4+CD25high+ Treg and number of skewed TRBV in 20 HBeAg positive patients were determined at baseline and following every 12 weeks during 96-week TDF treatment. The relationship among serum alanine aminotransferase (ALT) level, HBV DNA load, Treg frequency, and the number of skewed TRBV, respectively, was analyzed for CHB patients. Receiver operative characteristic curve was applied to analyze their diagnostic value for HBeAg SC. Results The number of skewed TRBV at week 48, Treg frequency at week 72, and ALT level at baseline could predict the HBeAg SC or non-SC in CHB patients during 96-week TDF treatment. Moreover, the positive correlation between ALT or HBV DNA and Treg levels or skewed TRBVs was significant in the SC group, but not in non-SC. Conclusions The predictive cutoff value of ALT for HBeAg SC was 178 U/L at baseline. Moreover, the ALT, Treg, and TRBV families would be associated with the prognosis and pathogenesis of CHB patients during TDF treatment.

Background:Acute-on-chronic liver failure(ACLF)is a life-threatening syndrome defined as acute decom-pensation in patients with chronic liver disease.Liver transplantation(LT)is the most effective treatment.We aimed to assess the impact of cirrhosis-related complications pre-LT on the posttransplant prognosis of patients with ACLF.Methods:This was an observational cohort study conducted between January 2018 and December 2020.Clinical characteristics,cirrhosis-related complications at LT and patient survival post-LT were collected.All liver recipients with ACLF were followed for 1 year post-LT.Results:A total of 212 LT recipients with ACLF were enrolled,including 75(35.4％)patients with ACLF-1,64(30.2％)with ACLF-2,and 73(34.4％)with ACLF-3.The median waiting time for LT was 11(4-24)days.The most prevalent cirrhosis-related complication was ascites(78.8％),followed by hepatic encephalopathy(57.1％),bacterial infections(48.1％),hepatorenal syndrome(22.2％)and gastrointestinal bleeding(11.3％).Survival analyses showed that patients with complications at LT had a significantly lower survival probability at both 3 months and 1 year after LT than those without complications(all P＜0.05).A simplified model was developed by assigning one point to each complication:transplantation for ACLF with cirrhosis-related complication(TACC)model.Risk stratification of TACC model identified 3 strata(≥4,=3,and≤2)with high,median and low risk of death after LT(P＜0.001).Moreover,the TACC model showed a comparable ability for predicting the outcome post-LT to the other four prognostic mod-els(chronic liver failure-consortium ACLF score,Chinese Group on the Study of Severe Hepatitis B-ACLF score,model for end-stage liver disease score and Child-Turcotte-Pugh score).Conclusions:The presence of cirrhosis-related complications pre-LT increases the risk of death post-LT in patients with ACLF.The TACC model based on the number of cirrhosis-related complications pre-LT could stratify posttransplant survival,which might help to determine transplant timing for ACLF.

The oral bacteriome, gut bacteriome, and gut mycobiome are associated with coronavirus disease 2019 (COVID-19). However, the oral fungal microbiota in COVID-19 remains unclear. This article aims to characterize the oral mycobiome in COVID-19 and recovered patients. Tongue coating specimens of 71 COVID-19 patients, 36 suspected cases (SCs), 22 recovered COVID-19 patients, 36 SCs who recovered, and 132 controls from Henan are collected and analyzed using internal transcribed spacer sequencing. The richness of oral fungi is increased in COVID-19 versus controls, and beta diversity analysis reveals separate fungal communities for COVID-19 and control. The ratio of Ascomycota and Basidiomycota is higher in COVID-19, and the opportunistic pathogens, including the genera Candida, Saccharomyces, and Simplicillium, are increased in COVID-19. The classifier based on two fungal biomarkers is constructed and can distinguish COVID-19 patients from controls in the training, testing, and independent cohorts. Importantly, the classifier successfully diagnoses SCs with positive specific severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies as COVID-19 patients. The correlation between distinct fungi and bacteria in COVID-19 and control groups is depicted. These data suggest that the oral mycobiome may play a role in COVID-19.

Microplastics (MP) and nanoplastics (NP) exist in the disposable plastic take-away containers. This study aims to determine the gut and oral microbiota alterations in the individuals frequently and occasionally consuming take-away food in disposable plastic containers (TFDPC), and explore the effect of micro/nanoplastics (MNP) reduction on gut microbiota in mice. TFDPC consumption are associated with greater presences of gastrointestinal dysfunction and cough. Both occasional and frequent consumers have altered gut and oral microbiota, and their gut diversity and evenness are greater than those of non-TFDPC consuming cohort. Multiple gut and oral bacteria are associated with TFDPC consumers, among which intestinal Collinsella and oral Thiobacillus are most associated with the frequent consumers, while intestinal Faecalibacterium is most associated with the occasional consumers. Although some gut bacteria associated with the mice treated with 500 µg NP and 500 µg MP are decreased in the mice treated with 200 µg NP, the gut microbiota of the three MNP groups are all different from the control group. This study demonstrates that TFDPC induces gut and oral microbiota alterations in the consumers, and partial reduction of the size and amount of MNP cannot rectify the MNP-induced gut microbial dysbiosis.

中医学领域的热证同现代医学中的发热存在差异,新型代谢模型是中西医融合的切入点,并能够弥合这种差异.现代医学认为,发热是致热源作用于下丘脑,导致体温调定点上调而引起的发热.从新型代谢模型来看,热证形成的病机是火行异常、热能在人体内积聚,是机体内化气和化阴过程失衡的表现.根据《伤寒论》六经理论,热证可以按照六经进行分类.阳明热证是获取能量物质的过程出现异常,太阳热证是水热排泄异常,少阳热证是能量物质在人体内代谢中间过程出现异常.这种异常包括氧化代谢和基因表达过程.致热源和感染性疾病导致的热证属于阴分发热.临床热证多以一经病变为主,累积多经,可以根据各经特征进行辨证施治.

Background: Hepatitis B (HepB) vaccination can effectively prevent the prevalence of hepatitis B virus (HBV) infection. However, the incidence of vaccination failure is about 5 similar to 10% and the underlying molecular mechanisms are poorly understood. T cells have an essential role in the recipient's immune response to vaccine, which could be elucidated by high-throughput sequencing (HTS) and bioinformatics analysis. Methods: We conducted HTS of the T cell receptor beta chain (TRB) complementarity-determining region 3 (CDR3) repertoires in eighteen positive responders (responders) and 10 negative responders (non-responders) who all had HepB vaccination, the repertoire features of BV, BJ and V-J genes and their diversity, respectively, were compared between the positive and negative responders using the Mann-Whitney test. Moreover, the relatively conserved motifs in CDR3 were revealed and compared to those in the other group's report. Results: The diversity of TRB CDR3 and the frequencies of BV27 and BV7-9 are significantly increased for HepB vaccine responders compared to those in non-responders. The motifs of CDR3s in BV27/J1-1, BV27/J2-5, and BV7-9/J2-5, respectively, were most expressed as "NTE", "QETQ", and "GG-Q (E)-ETQ". Moreover, the motif "KLNSPL" was determined in nearly 80% CDR3s in BV27/J1-6 from HepB vaccine responders for the first time. Conclusion: Our results present the comprehensive profiles of TRB CDR3 in the HepB vaccine responders and non-responders after standard vaccination protocol and determine the relatively conservative motifs of CDR3s that may respond to the HepB vaccine. Further results suggest that the profile of TRB repertoire could distinguish the HepB vaccine responders from non-responders and provide a new target for optimizing and improving the efficiency of the HepB vaccine.

We read with great interest the recent article published in Gut in which Yeoh et al demonstrated that gut microbiota composition of recovered patients with COVID-19 remained significantly distinct from uninfected controls.1 Persisting symptoms, also known as ‘long COVID-19’, have been reported in a significant proportion of patients following hospital discharge.2 3 Gut dysbiosis might link to long COVID-19 risks.1 Few studies have focused on the recovery process of gut microbiota following SARS-CoV-2 infection.\n\nHere, we conducted a prospective study to longitudinally monitor alterations of gut microbiota in patients with COVID-19 using 16S rDNA sequencing (detailed methods in online supplementary materials). Faecal microbiota was monitored at three timepoints, acute phase (from illness onset to viral clearance), convalescence (from viral clearance to 2 weeks after hospital discharge), postconvalescence (6 months after hospital discharge).### Supplementary data\n\n[gutjnl-2021-324090supp001.pdf]\n\nThe gut microbiota richness, measured by Chao 1 index, was obviously lower (p\u003c0.01, Wilcoxon rank-sum test; figure 1A) in the acute phase of COVID-19 (median 217, IQR 164–266) as compared with uninfected controls (median 432, IQR 332–468). There was a non-significant increase of the Chao 1 index from the acute phase (median 217, IQR 164–266) to the convalescence (median 241, IQR 202–279) and postconvalescence (median 259, IQR 193–302). A Bray-Curtis based principal coordinated analysis revealed that the overall microbial composition of …