The commensal microbiota is closely related to HBV infection and HBV-related liver diseases; however, how HBV and viral components dynamically affect the targeted organ liver microbiota is not well-known. In this study, an HBV-carrier mouse model established by HBsAg+ hepatocyte replacement in Fah-/- recipient mice, named HBs-HepR mice, was used to analyze the microbiota and metabolomics at the time of triggering the specific anti-HBV CD8+ T cell response in the liver. The composition and relative abundance of microbiota were both altered in the gut and liver of HBs-HepR mice. Particularly, increased Muribaculaceae and Alloprevotella, and decreased Lachnospiraceae-NK4A136 and Rikenella were observed in the gut; while increased Ralstonia and Geobacillus were observed in the liver of HBs-HepR mice. Furthermore, changes in microbial functions were revealed. There were no significant differences in the levels of SCFAs in fecal and serum; however, decreased propionic acid and acetic acid were detected in the livers of HBs-HepR mice, which was negatively related to the abundance of Geobacillus in the liver. Significantly decreased levels of 9 kinds of amino acids were detected in the feces of HBs-HepR mice, which was positively related to decreased Rikenella in the gut. A significant increase in L-glycine was observed in the liver and serum, positively related to the abundance of Geobaillus in the livers of HBs-HepR mice. In conclusion, chronic HBV infection imbalanced SCFA and amino acid metabolism by modulating microbiota in the liver, unlike in the gut, which was involved in the immune activation phase.

Summaries of the relationships between the microbiota and liver cirrhosis and their conclusions are not consistent. This study describes microbial differences in patients with liver cirrhosis by performing a meta-analysis.

We searched PubMed, Embase, Web of Science, and the Cochrane Library and collected related articles published before March 10, 2024. Ratio of autochthonous to non-autochthonous taxa was calculated as the cirrhosis dysbiosis ratio (CDR). Using a random-effects model, the standard mean deviation (SMD) and 95% confidence interval (CI) were calculated. We subsequently performed subgroup, sensitivity, and publication bias analyses. cirrhosis dysbiosis ratio.

A total of 53 eligible papers including 5076 participants were included. The pooled estimates revealed a moderately significant reduction in gut microbiome richness in patients with liver cirrhosis compared with controls, including the Shannon, Chao1, observed species, ACE, and PD indices, but no significant difference was observed for the Simpson index. Over 80% of the studies reported significant differences in β diversity. Families Enterobacteriaceae and Pasteurellaceae, belonging to the phylum Proteobacteria, along with the family Streptococcaceae and the genera Haemophilus, Streptococcus, and Veillonella, were significantly associated with liver cirrhosis compared to the control group. In contrast, the healthy group exhibited a higher abundance of the class Clostridia, particularly the families Lachnospiraceae and Ruminococcaceae, which are known for their diversity and role as common gut commensals. Furthermore, the class Bacilli, predominantly represented by the genus Streptococcus, was markedly enriched in the cirrhosis group.

The microbiota richness of liver cirrhosis patients was lower than that of healthy controls. Alterations in gut microbiota linked to liver cirrhosis were characterized by a decrease in Lachnospiraceae, Ruminococcaceae, and Clostridia and an enrichment of Enterobacteriaceae, Pasteurellaceae, Streptococcaceae, Bacilli, and Streptococcus.

The microbiome of the human intestine is a regulator of health that modulates immune response and plays an important role in metabolism. The diversity, and abundance of microbiota communities in the gut have been shown to change in cirrhosis and its complications. We aimed to review the current knowledge regarding microbiota alterations in cirrhosis, its potential differences according to etiology, and its role in the development of cirrhosis complications. A systematic search of the online bibliographic database up to July 2024 was performed. Randomized controlled trials and observational and cohort studies that included a total or at least a cohort of cirrhotic adult patients were enlisted for data extraction and analysis. A total of 73 publications were included for data extraction. Alpha diversity was found to decrease in cirrhotic patients in 30/38 (78%) of the studies, while beta diversity in 20/22 (90%) presented significant differences between healthy and cirrhotic groups. Proteobacteria significantly increased in 20/27 (74%) studies, followed by Actinobacteria and Fusobacteria, while 22/25 (88%) studies found either a reduction in cirrhotic patients or increased abundance in healthy controls for Firmicutes and Bacteroidetes. The most abundant genera in hepatic encephalopathy groups were pathobionts such as Enterococcus and Streptococcus, followed by Vellionella and Escherichia. Heterogeneity was found among studies regarding Alpha diversity in hepatocellular carcinoma (HCC) as it was decreased in three studies, indifferent in five, and increased in three studies in comparison to cirrhotic non-HCC patients. The dysbiosis of the gut microbiota is associated with cirrhosis and the development of complications such as hepatic encephalopathy and hepatocellular carcinoma.

With the rising prevalence of chronic liver diseases worldwide, there exists a need to diversify our artillery to incorporate a plethora of diagnostic and therapeutic methods to combat this disease. Currently, the most common causes of liver disease are non-alcoholic fatty liver disease, hepatitis, and alcoholic liver disease. Some of these chronic diseases have the potential to transform into hepatocellular carcinoma with advancing fibrosis. In this review, we analyse the relationship between the gut and liver and their significance in liver disease. This two-way relationship has interesting effects on each other in liver diseases. The gut microbiota, through its metabolites, influences the metabolism in numerous ways. Careful manipulation of its composition can lead to the discovery of numerous therapeutic potentials that can be applied in the treatment of various liver diseases. Numerous cohort studies with a pan-omics approach are required to understand the association between the gut microbiome and hepatic disease progression through which we can identify effective ways to deal with this issue.

Studies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF.

The gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups.

This study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.

Hepatitis B virus (HBV) is a hepatotropic non-cytopathic virus characterized by liver-specific gene expression. HBV infection highjacks bile acid metabolism, notably impairing bile acid uptake via sodium taurocholate cotransporting polypeptide (NTCP), which is a functional receptor for HBV entry. Concurrently, HBV infection induces changes in bile acid synthesis and the size of the bile acid pool. Conversely, bile acid facilitates HBV replication and expression through the signaling molecule farnesoid X receptor (FXR), a nuclear receptor activated by bile acid. However, in HepaRG cells and primary hepatocytes, FXR agonists suppress HBV RNA expression and the synthesis and secretion of DNA. In the gut, the size and composition of the bile acid pool significantly influence the gut microbiota. In turn, the gut microbiota impacts bile acid metabolism and innate immunity, potentially promoting HBV clearance. Thus, the bile acid-gut microbiota axis represents a complex and evolving relationship in the context of HBV infection. This review explores the interplay between bile acid and gut microbiota in HBV infection and discusses the development of HBV entry inhibitors targeting NTCP.

Hepatitis B virus (HBV), a common blood transmission pathogen worldwide, can lead to viral hepatitis, cirrhosis, liver cancer, and other liver diseases. In particular, occult hepatitis B virus infection (OBI) may be caused by an immune response leading to suppressed virus replication. Gut microbiota can change the immunity status of the human body and, therefore, affect the replication of HBV. Thus, to identify whether there are differences in gut microbiota between HBV carriers and OBI carriers, we collected fecal samples from 18 HBV carriers, 24 OBI blood donors, and also 20 healthy blood donors as negative control. After 16S sequencing, we found that the abundance of Faecalibacterium was significantly reduced in samples from OBI blood donors compared with those from healthy blood donors. Compared with samples from HBV carriers, the samples from OBI blood donors had a significantly increased abundance of Subdoligranulum, which might stimulate immune activation, thus inhibiting HBV replication and contributing to the formation of occult infection. Our findings revealed the potential role of gut microbiota in the formation of OBI and further provided a novel strategy for the treatment of HBV infection.IMPORTANCEOccult hepatitis B virus infection (OBI) is a special form of hepatitis B virus infection with hepatitis B surface antigen (HBsAg) positive and hepatitis B virus (HBV) DNA negative. Gut microbiota may contribute to the immune response leading to suppressed virus replication and, thus, participates in the development of OBI. The study on gut microbiota of OBI blood donors provides novel data considerably advancing our understanding of the immune mechanism for the determination of occult hepatitis B virus infection, which is helpful for improving the strategy of the treatment of HBV infection.

Hepatitis B virus (HBV) reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy. Paclitaxel (PTX) treatment has been identified as a potential trigger for HBV reactivation. This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo, which may inform new strategies for HBV antiviral treatment.

The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay, dual-luciferase reporter assay, quantitative real-time PCR, chromatin immunoprecipitation, and immunohistochemical staining. Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice.

PTX enhanced the levels of HBV 3.5-kb mRNA, HBV DNA, HBeAg, and HBsAg both in vitro and in vivo. PTX also promoted the activity of the HBV core promoter and transcription factor AP-1. Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation. Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17, NF-κB, and MAPK signaling pathways, with the pivotal common key molecule being AP-1. The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota.

PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1. These findings propose a novel molecular mechanism, underscoring the critical role of AP-1 in PTX-induced HBV reactivation.

Gut dysbiosis and subclinical intestinal damage are common in cirrhosis. The aim of this study was to examine the association of intestinal damage biomarkers (diamine oxidase [DAO], claudin 3, and intestinal fatty acid binding protein [I-FABP; FABP2]) with the state of the gut microbiota in cirrhosis. The blood levels of DAO were inversely correlated with blood levels of claudin 3, lipopolysaccharide (LPS), presepsin, TNF-α, and the severity of cirrhosis according to Child-Pugh scores. The blood level of I-FABP was directly correlated with the blood level of claudin 3 but not with that of DAO. Patients with small intestinal bacterial overgrowth (SIBO) had lower DAO levels than patients without SIBO. There was no significant difference in claudin 3 levels and I-FABP detection rates between patients with and without SIBO. The DAO level was directly correlated with the abundance of Akkermansiaceae, Akkermansia, Allisonella, Clostridiaceae, Dialister, Lactobacillus, Muribaculaceae, Negativibacillus, Ruminococcus, Thiomicrospiraceae, Verrucomicrobiae, and Verrucomicrobiota; and it was inversely correlated with the abundance of Anaerostipes, Erysipelatoclostridium, and Vibrio. The I-FABP level was directly correlated with Anaerostipes, Bacteroidia, Bacteroidota, Bilophila, Megamonas, and Selenomonadaceae; and it was inversely correlated with the abundance of Brucella, Pseudomonadaceae, Pseudomonas, and Vibrionaceae. The claudin 3 level was directly correlated with Anaerostipes abundance and was inversely correlated with the abundance of Brucella, Coriobacteriia, Eggerthellaceae, and Lactobacillus.

Fecal microbiota transplantation (FMT) offers a potential treatment avenue for hepatic encephalopathy (HE) by leveraging beneficial bacterial displacement to restore a balanced gut microbiome. The prevalence of HE varies with liver disease severity and comorbidities. HE pathogenesis involves ammonia toxicity, gut-brain communication disruption, and inflammation. FMT aims to restore gut microbiota balance, addressing these factors. FMT's efficacy has been explored in various conditions, including HE. Studies suggest that FMT can modulate gut microbiota, reduce ammonia levels, and alleviate inflammation. FMT has shown promise in alcohol-associated, hepatitis B and C-associated, and non-alcoholic fatty liver disease. Benefits include improved liver function, cognitive function, and the slowing of disease progression. However, larger, controlled studies are needed to validate its effectiveness in these contexts. Studies have shown cognitive improvements through FMT, with potential benefits in cirrhotic patients. Notably, trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care. Although evidence is promising, challenges remain: Limited patient numbers, varied dosages, administration routes, and donor profiles. Further large-scale, controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy. While FMT holds potential for HE management, ongoing research is needed to address these challenges, optimize protocols, and expand its availability as a therapeutic option for diverse hepatic conditions.

Invasive detection methods such as liver biopsy are currently the gold standard for diagnosing liver cirrhosis and can be used to determine the degree of liver fibrosis and cirrhosis. In contrast, non-invasive diagnostic methods, such as ultrasonography, elastography, and clinical prediction scores, can prevent patients from invasiveness-related discomfort and risks and are often chosen as alternative or supplementary diagnostic methods for liver fibrosis or cirrhosis. However, these non-invasive methods cannot specify the pathological grading and early diagnosis of the lesions. Recent studies have revealed that gut microbiome-based machine learning can be utilized as a non-invasive diagnostic technique for liver cirrhosis or fibrosis, but there is no evidence-based support. Therefore, this study conducted a systematic review and meta-analysis for the first time to investigate the accuracy of machine learning based on the gut microbiota in the prediction of liver fibrosis and cirrhosis.

A comprehensive and systematic search of publications published before April 2th, 2023 in PubMed, Cochrane Library, Embase, and Web of Science was conducted for relevant studies on the application of gut microbiome-based metagenomic sequencing modeling technology to the diagnostic prediction of liver cirrhosis or fibrosis. A bivariate mixed-effects model and Stata software 15.0 were adopted for the meta-analysis.

Ten studies were included in the present study, involving 11 prediction trials and 838 participants, 403 of whom were fibrotic and cirrhotic patients. Meta-analysis showed the pooled sensitivity (SEN) = 0.81 [0.75, 0.85], specificity (SEP) = 0.85 [0.77, 0.91], positive likelihood ratio (PLR) = 5.5 [3.6, 8.7], negative likelihood ratio (NLR) = 0.23 [0.18, 0.29], diagnostic odds ratio (DOR) = 24 [14, 41], and area under curve (AUC) = 0.86 [0.83-0.89]. The results demonstrated that machine learning methods had excellent potential to analyze gut microbiome data and could effectively predict liver cirrhosis or fibrosis. Machine learning provides a powerful tool for non-invasive prediction and diagnosis of liver cirrhosis or liver fibrosis, with broad clinical application prospects. However, these results need to be interpreted with caution due to limited clinical data.

Gut microbiome-based machine learning can be utilized as a practical, non-invasive technique for the diagnostic prediction of liver cirrhosis or fibrosis. However, most of the included studies applied the random forest algorithm in modeling, so a diversified prediction system based on microorganisms is needed to improve the non-invasive detection of liver cirrhosis or fibrosis.

The gut microbiota is a diverse ecosystem consisting of 100 trillion microbiomes. The interaction between the host's gut and distal organs profoundly impacts various functions such as metabolism, immunity, neurology, and nutrition within the human body. The liver, as the primary immune organ, plays a crucial role in maintaining immune homeostasis by receiving a significant influx of gut-derived components and toxins. Perturbations in gut microbiota homeostasis have been linked to a range of liver diseases. The advancements in sequencing technologies, such as 16S rRNA and metagenomics, have opened up new avenues for comprehending the intricate physiological interplay between the liver and the intestine. Metabolites produced by the gut microbiota function as signaling molecules and substrates, influencing both pathological and physiological processes. Establishing a comprehensive host-bacterium-metabolism axis holds tremendous potential for investigating the mechanisms underlying liver diseases. In this review, we have provided a summary of the detrimental effects of the gut-liver axis in chronic liver diseases, primarily focusing on hepatitis B virus-related chronic liver diseases. Moreover, we have explored the potential mechanisms through which the gut microbiota and its derivatives interact with liver immunity, with implications for future clinical therapies.

Cirrhosis is the end result of liver fibrosis in chronic liver diseases. Studying the mechanisms of its development and developing measures to slow down and regress it based on this knowledge seem to be important tasks for medicine. Currently, disorders of the gut-liver axis have great importance in the pathogenesis of cirrhosis. However, gut dysbiosis, which manifests as increased proportions in the gut microbiota of Bacilli and Proteobacteria that are capable of bacterial translocation and a decreased proportion of Clostridia that strengthen the intestinal barrier, occurs even at the pre-cirrhotic stage of chronic liver disease. This leads to the development of bacterial translocation, a process by which those microbes enter the blood of the portal vein and then the liver tissue, where they activate Kupffer cells through Toll-like receptor 4. In response, the Kupffer cells produce profibrogenic cytokines, which activate hepatic stellate cells, stimulating their transformation into myofibroblasts that produce collagen and other elements of the extracellular matrix. Blocking bacterial translocation with antibiotics, probiotics, synbiotics, and other methods could slow down the progression of liver fibrosis. This was shown in a number of animal models but requires further verification in long-term randomized controlled trials with humans.

Gut microbiota has been described as a new 'organ' that interferes with host physiology by its metabolites produced from the utilization and biotransformation of undigested food components. Fu Ling (FL), the sclerotia of fungi Wolfiporia cocos, contains β-glucan, which is a known natural polysaccharide with strong medicinal efficacy. This study endeavors to evaluate the fermentability of FL and polysaccharides extracted from its sclerotia. An in vitro fermentation of structurally characterized FL and its β-glucan by human fecal microbiota was conducted. Total bacterial count, pH change, short-chain fatty acid profile and microbiota profile were assessed post-fermentation. FL containing over 70% of β-(1 → 3) and (1 → 6)-glucans with a low degree of branching of 0.24 could enhance acetic acid (a major microbial metabolite) production. Both FL and its extracted β-glucan had similar modulation on microbial composition. They enriched Phascolarctobacterium faecium, Bacteroides dorei and Parabacteroides distasonis, all of which are shown to possess anti-inflammatory effects. FL polysaccharide can be utilized as a natural whole food for its potential health benefits to human gut bacteria.

Hepatitis B virus (HBV) infection is a global health epidemic that causes fatal complications, leading to liver cirrhosis and hepatocellular carcinoma. The link between HBV-related dysbiosis and specific bacterial taxa is still under investigation. Enterocloster is emerging as a new genus (formerly Clostridium), including Enterocloster bolteae, a gut pathogen previously associated with dysbiosis and human diseases such as autism, multiple sclerosis, and inflammatory bowel diseases. Its role in liver diseases, especially HBV infection, is not reported.

The fecal samples of eight patients with chronic HBV infection and ten healthy individuals were analyzed using the high-throughput culturomics approach and compared to 16S rRNA sequencing. Quantification of ethanol, known for its damaging effect on the liver, produced from bacterial strains enriched in chronic HBV was carried out by gas chromatography-mass spectrometry.

Using culturomics, 29,120 isolated colonies were analyzed by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-TOF); 340 species were identified (240 species in chronic HBV samples, 254 species in control samples) belonging to 169 genera and 6 phyla. In the chronic HBV group, 65 species were already known in the literature; 48 were associated with humans but had not been previously found in the gut, and 17 had never been associated with humans previously. Six species were newly isolated in our study. By comparing bacterial species frequency, three bacterial genera were serendipitously found with significantly enriched bacterial diversity in patients with chronic HBV: Enterocloster, Clostridium, and Streptococcus (p = 0.0016, p = 0.041, p = 0.053, respectively). However, metagenomics could not identify this enrichment, possibly concerning its insufficient taxonomical resolution (equivocal assignment of operational taxonomic units). At the species level, the significantly enriched species in the chronic HBV group almost all belonged to class Clostridia, such as Clostridium perfringens, Clostridium sporogenes, Enterocloster aldenensis, Enterocloster bolteae, Enterocloster clostridioformis, and Clostridium innocuum. Two E. bolteae strains, isolated from two patients with chronic HBV infection, showed high ethanol production (27 and 200 mM).

Culturomics allowed us to identify Enterocloster species, specifically, E. bolteae, enriched in the gut microbiota of patients with chronic HBV. These species had never been isolated in chronic HBV infection before. Moreover, ethanol production by E. bolteae strains isolated from the chronic HBV group could contribute to liver disease progression. Additionally, culturomics might be critical for better elucidating the relationship between dysbiosis and chronic HBV infection in the future.

The composition, viability and metabolic functionality of intestinal microbiota play an important role in human health and disease. Studies on intestinal microbiota are often based on fecal samples, because these can be sampled in a non-invasive way, although procedures for sampling, processing and storage vary. This review presents factors to consider when developing an automated protocol for sampling, processing and storing fecal samples: donor inclusion criteria, urine-feces separation in smart toilets, homogenization, aliquoting, usage or type of buffer to dissolve and store fecal material, temperature and time for processing and storage and quality control. The lack of standardization and low-throughput of state-of-the-art fecal collection procedures promote a more automated protocol. Based on this review, an automated protocol is proposed. Fecal samples should be collected and immediately processed under anaerobic conditions at either room temperature (RT) for a maximum of 4 h or at 4 °C for no more than 24 h. Upon homogenization, preferably in the absence of added solvent to allow addition of a buffer of choice at a later stage, aliquots obtained should be stored at either -20 °C for up to a few months or -80 °C for a longer period-up to 2 years. Protocols for quality control should characterize microbial composition and viability as well as metabolic functionality.

Drug induced liver injury (DILI) is a kind of liver dysfunction which caused by drugs, and gut microbiota could affect liver injury. However, the relationship between gut microbiota and its metabolites in DILI patients is not clear. The total gut microbiota DNA was extracted from 28 DILI patient and 28 healthy control volunteers (HC) and 16S rDNA gene were amplified. Next, differentially metabolites were screened. Finally, the correlations between the diagnostic strains and differentially metabolites were studied.The richness and uniformity of the bacterial communities decreased in DILI patients, and the structure of gut microbiota changed obviously. Enterococcus and Veillonella which belong to Firmicutes increased in DILI, and Blautia and Ralstonia which belong to Firmicutes, Dialister which belongs to Proteobacteria increased in HC. In addition, these diagnostic OTUs of DILI were associated with the DILI damage mechanism. On the other hands, there were 66 differentially metabolites between DILI and HC samples, and these metabolites were mainly enriched in pyrimidine metabolism and steroid hormone biosynthesis pathways. Furthermore, the collinear network map of the key microbiota-metabolites were constructed and the results indicated that Cortodoxone, Prostaglandin I1, Bioyclo Prostaglandin E2 and Anacardic acid were positively correlated with Blautia and Ralstonia, and negatively correlated with Veillonella.This study analyzed the changes of DILI from the perspective of gut microbiota and metabolites. Key strains and differentially metabolites of DILI were screened and the correlations between them were studied. This study further illustrated the mechanism of DILI.

To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis.

This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed.

Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment.

BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).

The aim was to evaluate the relationship between gut dysbiosis and hemodynamic changes (hyperdynamic circulation) in cirrhosis, and between hemodynamic changes and complications of this disease. This study included 47 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Echocardiography with a simultaneous assessment of blood pressure and heart rate was performed to assess systemic hemodynamics. Patients with hyperdynamic circulation had more severe cirrhosis, lower albumin, sodium and prothrombin levels, higher C-reactive protein, aspartate aminotransferase and total bilirubin levels, and higher incidences of portopulmonary hypertension, ascites, overt hepatic encephalopathy, hypoalbuminemia, hypoprothrombinemia, systemic inflammation, and severe hyperbilirubinemia than patients with normodynamic circulation. Patients with hyperdynamic circulation compared with those with normodynamic circulation had increased abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Fusobacteria, Micrococcaceae, Intestinobacter, Clostridium sensu stricto, Proteus and Rumicoccus, and decreased abundance of Bacteroidetes, Bacteroidaceae, Holdemanella, and Butyrivibrio. The systemic vascular resistance and cardiac output values correlated with the abundance of Proteobacteria, Enterobacteriaceae, Bacilli, Streptococcaceae, Lactobacillaceae, Micrococcaceae, and Fusobacteria. Heart rate and cardiac output value were negatively correlated with the abundance of Bacteroidetes. The mean pulmonary artery pressure value was positively correlated with the abundance of Proteobacteria and Micrococcaceae, and negatively with the abundance of Holdemanella.

Observational studies have provided evidence of a close association between gut microbiota and the progression of chronic hepatitis B (CHB). However, establishing a causal relationship between gut microbiota and CHB remains a subject of investigation.

Genome-wide association study (GWAS) summary data of gut microbiota came from the MiBioGen consortium, while the GWAS summary data of CHB came from the Medical Research Council Integrative Epidemiology Unit (IEU) Open GWAS project. Based on the maximum likelihood (ML), Mendelian randomization (MR)-Egger regression, inverse variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and weighted-mode and weighted-median methods, we conducted a bidirectional, two-sample, MR analysis to explore the causal relationship between the gut microbiota and CHB. Additionally, we evaluated the genetic associations between individual gut microbes and CHB using the Linkage disequilibrium score regression (LDSC) program.

According to the IVW method estimates, genetically predicted class Alphaproteobacteria (odds ratio [OR] = 0.57; 95% confidence interval [CI], 0.34-0.96; false discovery rate [FDR] = 0.046), genus Family XIII AD3011 group (OR = 0.60; 95% CI, 0.39-0.91; FDR = 0.026), genus Prevotella 7 (OR = 0.73; 95% CI, 0.56-0.94; FDR = 0.022) exhibited a protective effect against CHB. On the other hand, family Family XIII (OR = 1.79; 95% CI, 1.03-3.12; FDR = 0.061), genus Eggerthella group (OR = 1.34; 95% CI, 1.04-1.74; FDR = 0.043), genus Eubacterium ventriosum group (OR = 1.59; 95% CI, 1.01-2.51; FDR = 0.056), genus Holdemania (OR = 1.35; 95% CI, 1.00-1.82; FDR = 0.049), and genus Ruminococcus gauvreauii group (OR = 1.69; 95% CI, 1.10-2.61; FDR = 0.076) were associated with an increased risk of CHB. The results from LDSC also indicated a significant genetic correlation between most of the aforementioned gut microbiota and CHB. Our reverse MR analysis demonstrated no causal relationship between genetically predicted CHB and gut microbiota, and we observed no significant horizontal pleiotropy or heterogeneity of instrumental variables (IVs).

In this study, we identified three types of gut microbiota with a protective effect on CHB and five types with an adverse impact on CHB. We postulate that this information will facilitate the clinical prevention and treatment of CHB through fecal microbiota transplantation.

Decreased muscle mass and function, also known as sarcopenia, is common in patients with cirrhosis and is associated with a poor prognosis. Although the pathogenesis of this disorder has not been fully elucidated, a disordered gut-muscle axis probably plays an important role. Decreased barrier function of the gut and liver, gut dysbiosis, and small intestinal bacterial overgrowth (SIBO) can lead to increased blood levels of ammonia, lipopolysaccharides, pro-inflammatory mediators, and myostatin. These factors have complex negative effects on muscle mass and function. Drug interventions that target the gut microbiota (long-term use of rifaximin, lactulose, lactitol, or probiotics) positively affect most links of the compromised gut-muscle axis in patients with cirrhosis by decreasing the levels of hyperammonemia, bacterial translocation, and systemic inflammation and correcting gut dysbiosis and SIBO. However, although these drugs are promising, they have not yet been investigated in randomized controlled trials specifically for the treatment and prevention of sarcopenia in patients with cirrhosis. No data exist on the effects of fecal transplantation on most links of gut-muscle axis in cirrhosis; however, the results of animal experimental studies are promising.

Viral gastroenteritis is the most common viral illness that affects the gastrointestinal (GI) tract, causing inflammation and irritation of the lining of the stomach and intestines. Common signs and symptoms associated with this condition include abdominal pain, diarrhea, and dehydration. The infections commonly involved in viral gastroenteritis are rotavirus, norovirus, and adenovirus, which spread through the fecal-oral and contact routes and cause non-bloody diarrhea. These infections can affect both immunocompetent and immunocompromised individuals. Since the pandemic in 2019, coronavirus gastroenteritis has increased in incidence and prevalence. Morbidity and mortality rates from viral gastroenteritis have declined significantly over the years due to early recognition, treatment with oral rehydration salts, and prompt vaccination. Improved sanitation measures have also played a key role in reducing the transmission of infection. In addition to viral hepatitis causing liver disease, herpes virus, and cytomegalovirus are responsible for ulcerative GI disease. They are associated with bloody diarrhea and commonly occur in im-munocompromised individuals. Hepatitis viruses, Epstein-Barr virus, herpesvirus 8, and human papillomavirus have been involved in benign and malignant diseases. This mini review aims to list different viruses affecting the GI tract. It will cover common symptoms aiding in diagnosis and various important aspects of each viral infection that can aid diagnosis and management. This will help primary care physicians and hospitalists diagnose and treat patients more easily.

Gut microbiota is the largest population of microorganisms and is closely related to health. Many studies have explored changes in gut microbiota in viral hepatitis. However, the correlation between gut microbiota and the occurrence and progression of viral hepatitis has not been fully clarified.

PubMed and BioProject databases were searched for studies about viral hepatitis disease and 16S rRNA gene sequencing of gut microbiota up to January 2023. With bioinformatics analyses, we explored changes in microbial diversity of viral hepatitis, screened out crucial bacteria and microbial functions related to viral hepatitis, and identified the potential microbial markers for predicting risks for the occurrence and progression of viral hepatitis based on ROC analysis.

Of the 1389 records identified, 13 studies met the inclusion criteria, with 950 individuals including 656 patient samples (HBV, n = 546; HCV, n = 86; HEV, n = 24) and 294 healthy controls. Gut microbial diversity is significantly decreased as the infection and progression of viral hepatitis. Alpha diversity and microbiota including Butyricimonas, Escherichia-Shigella, Lactobacillus, and Veillonella were identified as the potential microbial markers for predicting the risk of development of viral hepatitis (AUC>0.7). Microbial functions including tryptophan metabolism, fatty acid biosynthesis, lipopolysaccharide biosynthesis, and lipid metabolism related to the microbial community increased significantly as the development of viral hepatitis.

This study demonstrated comprehensively the gut microbiota characteristics in viral hepatitis, screened out crucial microbial functions related to viral hepatitis, and identified the potential microbial markers for predicting the risk of viral hepatitis.

Hepatitis B virus (HBV) causes chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma. The evolution of human gut microbiota during the progression of HBV-related liver diseases remains unclear. Therefore, we prospectively enrolled patients with HBV-related liver diseases and healthy individuals. Through 16S ribosomal RNA amplicon sequencing, we characterized the gut microbiota of the participants and predicted the functions of microbial communities.

We analyzed the gut microbiota of 56 healthy controls and 106 patients with HBV-related liver disease [14 with resolved HBV infection, 58 with CHB, and 34 with advanced liver disease (15 with liver cirrhosis and 19 with hepatocellular carcinoma)]. Patients with HBV-related liver disease exhibited a higher degree of bacterial richness (all P < 0.05) than did healthy controls. Beta diversity analyses revealed a distinct clustering pattern between healthy controls and patients with HBV-related liver disease (all P < 0.05). The composition of bacteria (from the phylum level to the genus level) varied across the stages of liver disease. Linear discriminant analysis effect size revealed multiple taxa that differ significantly in abundance between healthy controls and patients with HBV-related liver disease; however, fewer differences were observed among patients with resolved HBV infection, those with CHB, and those with advanced liver disease. The ratio of Firmicutes to Bacteroidetes was increased in all three patient groups compared with the ratio in healthy controls (all P < 0.001). The analysis of the sequencing data by using PICRUSt2 revealed the changes in microbial functions with disease progression.

The diversity and composition of gut microbiota appear to vary significantly between healthy controls and patients at different stages of HBV-related liver disease. The understanding of gut microbiota may provide novel therapeutic options in these patients.

Small intestinal bacterial overgrowth (SIBO) is associated with numerous manifestations of cirrhosis. To determine whether the presence of SIBO affects the prognosis in cirrhosis was the aim of the study.

This prospective cohort study included 50 patients. All participants underwent a lactulose hydrogen breath test for SIBO. The follow-up period was 4 years.

SIBO was detected in 26 (52.0%) patients: in 10 (52.6%) patients with compensated cirrhosis and in 16 (51.6%) ones with decompensated cirrhosis. Twelve (46.2%) patients with SIBO and four (16.7%) patients without SIBO died within 4 years (p = 0.009). Among patients with decompensated cirrhosis, 8 (50.0%) patients with SIBO and 3 (20.0%) patients without SIBO died (p = 0.027). Among patients with compensated cirrhosis, four (40.0%) patients with SIBO and one (11.1%) patient without SIBO died (p = 0.045). Among patients with SIBO, there was no difference in mortality between patients with compensated and decompensated cirrhosis (p = 0.209). It was the same for patients without SIBO (p = 0.215). SIBO affects the prognosis only in the first year of follow-up in decompensated cirrhosis, and only in subsequent years in compensated cirrhosis. Presence of SIBO (p = 0.028; HR = 4.2(1.2-14.9)) and serum albumin level (p = 0.027) were significant independent risk factors for death in cirrhosis.

SIBO is associated with poor prognosis in cirrhosis.

Primary sclerosing cholangitis (PSC) offers unique opportunities to explore the gut-liver axis owing to the close association between liver disease and colonic inflammation. It is well established that the gut microbiota in people with PSC differs from that of healthy individuals, but details of the microbial factors that demarcate PSC from inflammatory bowel disease (IBD) without PSC are poorly understood. In this Review, we aim to provide an overview of the latest literature on the gut microbiome in PSC and PSC with IBD, critically examining hypotheses on how microorganisms could contribute to the pathogenesis of PSC. A particular emphasis will be put on pathogenic features of the gut microbiota that might explain the occurrence of bile duct inflammation and liver disease in the context of IBD, and we postulate the potential existence of a specific yet unknown factor related to the gut-liver axis as causative in PSC. Available data are scrutinized in the perspective of therapeutic approaches related to the gut-liver axis.

A growing body of evidence suggested that gut microbiota is associated with liver diseases through the gut-liver axis. The imbalance of gut microbiota could be correlated with the occurrence, development, and prognosis of a series of liver diseases, including alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, primary sclerosing cholangitis (PSC), and hepatocellular carcinoma (HCC). Fecal microbiota transplantation (FMT) seems to be a method to normalize the patient's gut microbiota. This method has been traced back to the 4th century. In recent decade, FMT has been highly regarded in several clinical trials. As a novel approach to reconstruct the intestinal microecological balance, FMT has been used to treat the chronic liver diseases. Therefore, in this review, the role of FMT in the treatment of liver diseases was summarized. In addition, the relationship between gut and liver was explored through the gut-liver axis, and the definition, objectives, advantages, and procedures of FMT were described. Finally, the clinical value of FMT therapy in liver transplant (LT) recipients was briefly discussed.

The interactions between the microbiota and the human host can affect the physiological functions of organs (such as the brain, liver, gut, etc.). Accumulating investigations indicate that the imbalance of microbial community is closely related to the occurrence and development of diseases. Thus, the identification of potential links between microbes and diseases can provide insight into the pathogenesis of diseases. In this study, we propose a deep learning framework (MDAGCAN) based on graph convolutional attention network to identify potential microbe-disease associations. In MDAGCAN, we first construct a heterogeneous network consisting of the known microbe-disease associations and multi-similarity fusion networks of microbes and diseases. Then, the node embeddings considering the neighbor information of the heterogeneous network are learned by applying graph convolutional layers and graph attention layers. Finally, a bilinear decoder using node embedding representations reconstructs the unknown microbe-disease association. Experiments show that our method achieves reliable performance with average AUCs of 0.9778 and 0.9454 ± 0.0038 in the frameworks of Leave-one-out cross validation (LOOCV) and 5-fold cross validation (5-fold CV), respectively. Furthermore, we apply MDAGCAN to predict latent microbes for two high-risk human diseases, i.e., liver cirrhosis and epilepsy, and results illustrate that 16 and 17 out of the top 20 predicted microbes are verified by published literatures, respectively. In conclusion, our method displays effective and reliable prediction performance and can be expected to predict unknown microbe-disease associations facilitating disease diagnosis and prevention.

Clinacanthus nutans (Burm.f.) Lindau (C. nutans) has been used in the therapy of hepatitis B (HB) and is effective; however, the mechanism of action has not been elucidated.

To investigate the protective effects of C. nutans aqueous extract on the hepatitis B virus (HBV) mouse model based on correlation analysis between gut microbiota and liver metabolomics.

We firstly constructed the animal model by high-pressure injection of pcDNA3.1(+)/HBV plasmid into the tail vein and treated it with C. nutans. The biomarkers and inflammatory cytokines of HB were detected by enzyme-linked immunosorbent assay and quantitative PCR; the Illumina-MiSeq platform was used for investigating gut microbiota; the LC-MS/MS method was utilized on screening liver tissue metabolites; multiomics joint analysis was performed using the R program.

Compared with the modeling group, C. nutans significantly decreased the expression levels of HBsAg, IL-1β, TNF-α(P < 0.05) in the serum, and cccDNA (P < 0.05) in the liver tissues of mice. C. nutans dramatically reduced the ratio of Firmicutes and Bacteroidetes (P < 0.05) and significantly declined the proportion of Lactobacillaceae and Lactobacillus(P < 0.05), dramatically increasing the relative abundance of Bacteroidales_S24-7_group, Rikenellaceae, and Alistipes(P < 0.05); LC-MS/MS analysis results showed that C. nutans dramatically upregulate hippuric acid, L-histidine, trehalose, D-threitol, and stachyose and downregulate uridine 5'-diphosphate, cholic acid, trimethylamine N-oxide, CDP-ethanolamine, and phosphorylcholine (P < 0.05). The correlation analysis revealed that C. nutans affects the related metabolite levels of hippuric acid and cholic acid through the modulation of crucial bacteria (Alistipes) (P < 0.01), exerting specific anti-inflammatory effects.

These results suggest that C. nutans exerts protective effects in HBV model mice, showing the therapeutic potential for anti-HBV infection.

In this cross-sectional study, we hypothesized that a high dietary ratio of omega-6 (n-6) to omega-3 (n-3) fatty acids could be associated with an altered gut bacterial composition and with the disease severity in patients with nonalcoholic fatty liver disease (NAFLD). A total of 101 NAFLD patients were included in the study, of which 63 underwent a liver biopsy. All 101 patients completed a 14-day food and activity record. Ebispro 2016 professional software was used to calculate individual macronutrients and micronutrients consumed. Patients were grouped into 3 quantiles (Q) according to a low (Q1: <6.1, n = 34), moderate (Q2: 6.1-7.8, n = 33), or high (Q3: >7.8, n = 34) dietary n-6/n-3 ratio. Stool samples were analyzed using 16S rRNA gene sequencing. Spearman correlation coefficients and principal coordinate analysis were used to detect differences in the bacterial composition of the gut microbiota. The median dietary n-6/n-3 ratio of all patients was 6.7 (range, 3.1-14.9). No significant associations between the dietary n-6/n-3 ratio and the gut microbiota composition or disease severity were observed. However, the abundance of specific bacteria such as Catenibacterium or Lactobacillus ruminis were found to be positively correlated and the abundance of Clostridium were negatively correlated with dietary n-6 fatty acid intake. The results indicate that a high dietary n-6/n-3 ratio is probably not a highly relevant factor in the pathogenesis of human NAFLD. Further studies are needed to clarify the importance of interactions between gut bacterial taxa and n-6 fatty acids in the pathophysiology of NAFLD.

Our previous clinical study has shown that the exopolysaccharide (EPS) produced by a plant-derived lactic acid bacterium, Lactobacillus paracasei IJH-SONE68, improves chronic allergy status in humans. In addition, an inhibition of visceral fat accumulation was observed following the intake of EPS during animal experimentation. In the present study, we have further evaluated the health-promoting effects of a spray-dried powder of pineapple juice that is fermented with the IJH-SONE68 strain. This was conducted in a double-blind, randomized, placebo-controlled, parallel-group clinical trial at Hiroshima University from May 2019 to July 2021. Eighty healthy volunteers at range of ages 23-70, with a body mass index between 25 and 29.99, were enrolled. After the 12 weeks of the experimental period were complete, although the average visceral fat area in both groups similarly decreased, there was no significant difference in the content of visceral fat area or in the obesity-related physical parameters in both groups. Further, we found that the serum liver function indices (AST and ALT) in the test group decreased within a statistically determined trend (p = 0.054). The fecal microflora analysis revealed, in the test group, a statistically significant increase in the relative abundance changes within Anaerostipes, which has been reported to help suppress hepatic inflammation.

The microbes and metabolomics of microbiota dysbiosis in the gut in the different phases of hepatitis B virus (HBV) infection are not fully understood.

To investigate the specific gut microbiota and metabolites of the immune-tolerant (IT) and immune-active (IA) phases of chronic hepatitis B (CHB).

Clinical fecal samples from healthy individuals and patients in the IT and IA phases of HBV infection were collected. Next, non-target metabolomics, bioinformatics, and 16S rDNA sequencing analyses were performed.

A total of 293 different metabolites in 14 phyla, 22 classes, 29 orders, 51 families, and 190 genera were identified. The four phyla of Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the most abundant, accounting for 99.72%, 99.79%, and 99.55% in the healthy controls, IT-phase patients, and IA-phase patients, respectively. We further identified 16 genera with different richness in the IT phase and IA phase of HBV infection. Of the 134 named metabolites, 57 were upregulated and 77 were downregulated. A total of 101 different metabolic functions were predicted in this study, with 6 metabolic pathways having the highest enrichments, namely carbohydrate metabolism (14.85%), amino acid metabolism (12.87%), lipid metabolism (11.88%), metabolism of cofactors and vitamins (11.88%), xenobiotic biodegradation (9.9%), and metabolism of terpenoids and polyketides (7.92%).

These findings provide observational evidence of compositional alterations of the gut microbiome and some related metabolites in patients with IT-phase or IA-phase HBV infection. Further studies should investigate whether microbiota modulation can facilitate the progression of CHB and the cause-effect relationship between the gut microbiota and CHB.

Gut microbial dysbiosis during the development of Hepatitis C virus and liver-related diseases is not well studied. Nowadays, HCV and liver cirrhosis are the major concerns that cause gut bacterial alteration, which leads to dysbiosis. For this purpose, the present study was aimed at correlating the gut bacterial community of the control group in comparison to HCV and liver cirrhotic patients. A total of 23 stool samples were collected, including control (9), liver cirrhotic (8), and HCV (6). The collected samples were subjected to 16S rRNA Illumina gene sequencing. In comparison with control, a significant gut bacterial alteration was observed in the progression of HCV and liver cirrhosis. Overall, Firmicutes were significantly abundant in the whole study. No significant difference was observed in the alpha diversity of the control and patient studies. Additionally, the beta diversity based on non-metric multidimensional scaling (NMDS) has a significant difference (p = 0.005) (ANOSIM R² = 0.14) in all groups. The discriminative results based on the LEfSe tool revealed that the HCV-infected patients had higher Enterobacteriaceae and Enterobacterial, as well as Lactobacillus and Bacilli in comparison than the liver-cirrhotic patients. These taxa were significantly different from the control group (p < 0.05). Regarding prospects, a detailed analysis of the function through metagenomics and transcriptomics is needed.

Bacterial translocation exacerbates the hyperdynamic circulation observed in cirrhosis and contributes to a more severe disease course. Probiotics may reduce bacterial translocation and may therefore be useful to redress the circulatory imbalance.

To investigate the effect of probiotics on hemodynamic parameters, systemic inflammation, and complications of cirrhosis in this randomized placebo-controlled trial.

This single-blind randomized placebo-controlled study included 40 patients with Child-Pugh class B and C cirrhosis; 24 patients received probiotics (Saccharomyces boulardii) for 3 mo, and 16 patients received a placebo over the same period. Liver function and the systemic hemodynamic status were evaluated pre- and post-intervention. Echocardiography and simultaneous blood pressure and heart rate monitoring were performed to evaluate systemic hemodynamic indicators. Cardiac output and systemic vascular resistance were calculated.

Following a 3-mo course of probiotics in comparison to the control group, we observed amelioration of hyperdynamic circulation [a decrease in cardiac output (P = 0.026) and an increase in systemic vascular resistance (P = 0.026)] and systemic inflammation [a decrease in serum C-reactive protein levels (P = 0.044)], with improved liver function [an increase in serum albumin (P = 0.001) and a decrease in the value of Child-Pugh score (P = 0.001)] as well as a reduction in the severity of ascites (P = 0.022), hepatic encephalopathy (P = 0.048), and cholestasis [a decrease in serum alkaline phosphatase (P = 0.016) and serum gamma-glutamyl transpeptidase (P = 0.039) activity] and an increase in platelet counts (P < 0.001) and serum sodium level (P = 0.048).

Probiotic administration was associated with amelioration of hyperdynamic circulation and the associated complications of cirrhosis.

The compositional balance of intestinal microbiota plays an important role in maintaining homeostasis. This study aimed to investigate the intestinal flora of hepatitis B virus-associated liver cirrhosis (HBV-LC) with or without hepatic encephalopathy (HE) and how it relates to the disease. A total of 20 patients with HBV-LC were enrolled in this study, along with 10 healthy adults. The participants were divided into HE group, non-HE group, and control group. Fecal samples were collected under the condition of patients' daily diet, and the 16S rRNA test was performed for each fecal sample. The relative abundance of Bacteroidia, Streptococcaceae, Streptococcus, Veillonella, Bacteroidales, Lactobacillales, Pasteurellales, and Veillonella parvula increased in the HBV-LC group. Meanwhile, the relative weights of Pasteurellales, Pasteurellaceae, Haemophilus, and Selenomonas significantly increased in the HE group. Furthermore, in the non-HE group, the relative abundance of Veillonella increased. Intestinal microbiota was significantly different from controls with respect to a lack of potentially beneficial autochthonous bacteria and overgrowth of potentially pathogenic genera in patients with HBV-LC. Moreover, there was a greater change in the relative abundance of intestinal flora when complicated with HE.

Gut dysbiosis and changes in body composition (i.e., a decrease in the proportion of muscle mass and an increase in extracellular fluid) are common in cirrhosis.

To study the relationship between the gut microbiota and body composition in cirrhosis.

This observational study included 46 patients with cirrhosis. Stool microbiome was assessed using 16S rRNA gene sequencing. Multifrequency bioelectrical impedance analysis was performed to assess body composition in these patients.

An increase in fat mass and a decrease in body cell mass were noted in 23/46 (50.0%) and 15/46 (32.6%) patients, respectively. Changes in the gut microbiome were not independently associated with the fat mass percentage in cirrhosis. The abundance of Bacteroidaceae (P = 0.041) and Eggerthella (P = 0.001) increased, whereas that of Erysipelatoclostridiaceae (P = 0.006), Catenibacterium (P = 0.021), Coprococcus (P = 0.033), Desulfovibrio (P = 0.043), Intestinimonas (P = 0.028), and Senegalimassilia (P = 0.015) decreased in the gut microbiome of patients with body cell mass deficiency. The amount of extracellular fluid increased in 22/46 (47.6%) patients. Proteobacteria abundance (P < 0.001) increased, whereas Firmicutes (P = 0.023), Actinobacteria (P = 0.026), Bacilli (P = 0.008), Anaerovoraceceae (P = 0.027), Christensenellaceae (P = 0.038), Eggerthellaceae (P = 0.047), Erysipelatoclostridiaceae (P = 0.015), Erysipelotrichaceae (P = 0.003), Oscillospiraceae (P = 0.024), Rikenellaceae (P = 0.002), Collinsella (P = 0.030), Hungatella (P = 0.040), Peptococcaceae (P = 0.023), Slackia (P = 0.008), and Senegalimassilia (P = 0.024) abundance decreased in these patients. Patients with clinically significant ascites (n = 9) had a higher abundance of Proteobacteria (P = 0.031) and a lower abundance of Actinobacteria (P = 0.019) and Bacteroidetes (P = 0.046) than patients without clinically significant ascites (n = 37).

Changes in the amount of body cell mass and extracellular fluid are associated with changes in the gut microbiome in cirrhosis patients.