Changes in the intestinal microbiota of individuals with non-alcoholic fatty liver disease based on sequencing: An updated systematic review and meta-analysis.

BACKGROUND: Alterations in the composition and abundance of the intestinal microbiota occur in non-alcoholic fatty liver disease (NAFLD). However, the results are inconsistent because of differences in the study design, subject area, and sequencing methodology. In this study, we compared the diversity and abundance of the intestinal microbiota of patients with NAFLD and healthy individuals through a systematic review and meta-analysis. METHODS: Three databases (PubMed, EMBASE, and Cochrane Library) were searched from their inception to March 20, 2023. A meta-analysis was performed using Stata software to analyze variations in the richness and abundance of the intestinal microbiota in patients with NAFLD. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used for quality assessment. RESULTS: A total of 28 articles were included. Shannon diversity was reduced in patients with NAFLD (SMD = -0.24 (95% CI -0.43-0.05, I2 = 71.7%). The relative abundance of Ruminococcus, Faecalibacterium, and Coprococcus all decreased, with total SMDs of -0.96 (95% CI -1.29 to -0.63, I2 = 4.8%), -1.13 (95% CI -2.07 to -0.19, I2 = 80.5%), and -1.66 (95% CI -3.04 to -0.28, I2 = 91.5%). Escherichia was increased in individuals with NAFLD (SMD = 1.78, 95% CI 0.12 to 3.45, I2 = 94.4%). CONCLUSION: Increasing the species diversity and altering the abundance of specific gut microbiota, including Coprococcus, Faecalibacterium, Ruminococcus, and Escherichia, may be beneficial for improving NAFLD.

Bacteroides fragilis aggravates high-fat diet-induced non-alcoholic fatty liver disease by regulating lipid metabolism and remodeling gut microbiota.

Gut microbiota dysbiosis is a prominent determinant that significantly contributes to the disruption of lipid metabolism. Consequently, it is essential to the occurrence and development of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the connection between diet and symbiotic gut microbiota in the progression of NAFLD remains uncertain. The purpose of this study was to explore the role of supplementing commensal Bacteroides fragilis (B. fragilis) on lipid metabolism, gut microbiota, and metabolites in high-fat diet (HFD)-fed mice, elucidating the impact of gut microbiota and metabolites on the development of NAFLD. Our study revealed that supplementation with B. fragilis exacerbated both weight gain and obesity in mice. B. fragilis exacerbated blood glucose levels and liver dysfunction in mice. Furthermore, an increase in liver lipid accumulation and the upregulation of genes correlated with lipid metabolism were observed in mice. Under an HFD, supplementation of commensal B. fragilis resulted in alterations in the gut microbiota, notably a significant increase in Desulfovibrionaceae, which led to elevated endotoxin levels and thereby influenced the progression of NAFLD. It was interesting that the simultaneous examination of gut microbiota metabolites revealed a more pronounced impact of diet on short-chain fatty acids. This study represented the pioneering investigation into the impact of B. fragilis on NAFLD. Our findings demonstrated that B. fragilis induced dysregulation in the intestinal microbiota, leading to elevated levels of lipopolysaccharide and dysfunction in glucose and lipid metabolism, thereby exacerbating NAFLD.IMPORTANCESome intestinal symbiotic microbes are involved in the occurrence of the metabolic disorders. Our study investigated the impact of supplementing commensal Bacteroides fragilis on host metabolism in high-fat diet-fed mice. Research results indicated that adding a specific bacterial strain to the complex intestinal microecology can worsen metabolic conditions. This effect mainly affects the structural diversity of intestinal microorganisms, the increase in harmful bacteria in the gut, and the elevation of endotoxin levels, blood glucose, and lipid metabolism, thereby impacting the progression of non-alcoholic fatty liver disease (NAFLD). Understanding the principles that govern the establishment of microbial communities comprising multiple species is crucial for preventing or repairing dysfunctions in these communities, thereby enhancing host health and facilitating disease treatment. This study demonstrated that gut microbiota dysbiosis could contribute to metabolic dysfunction and provides new insights into how to promote gut microbiota in the prevention and therapy of NAFLD.

Gut Microbiota Plays Essential Roles in Soyasaponin's Preventive Bioactivities against Steatohepatitis in the Methionine and Choline Deficient (MCD) Diet-Induced Non-Alcoholic Steatohepatitis (NASH) Mice.

SCOPE: Gut microbiota (GM) is involved in nonalcoholic steatohepatitis (NASH) development. Phytochemicals soyasaponins can prevent NASH possibly by modulating GM. This study aims to investigate the preventive bioactivities of soyasaponin monomers (SS-A1 and SS-Bb) against NASH and explores the mechanisms by targeting GM. METHODS AND RESULTS: Male C57BL/6 mice are fed with methionine and choline deficient (MCD) diet containing SS-A1 , SS-Bb, or not for 16 weeks. Antibiotics-treated pseudo germ-free (PGF) mice are fed with MCD diet containing SS-A1 , SS-Bb, or not for 8 weeks. GM is determined by 16S rRNA amplicon sequencing. Bile acids (BAs) are measured by UPLC-MS/MS. In NASH mice, SS-A1 and SS-Bb alleviate steatohepatitis and fibrosis, reduce ALT, AST, and LPS in serum, decrease TNF-α, IL-6, α-SMA, triglycerides, and cholesterol in liver. SS-A1 and SS-Bb decrease Firmicutes, Erysipelotrichaceae, unidentified-Clostridiales, Eggerthellaceae, Atopobiaceae, Aerococcus, Jeotgalicoccus, Gemella, Rikenella, increase Proteobacteria, Verrucomicrobia, Akkermansiaceae, Romboutsia, and Roseburia. SS-A1 and SS-Bb alter BAs composition in liver, serum, and feces, activate farnesoid X receptor (FXR) in liver and ileum, increase occludin and ZO-1 in intestine. However, GM clearance abrogates the preventive bioactivities of SS-A1 and SS-Bb against NASH. CONCLUSION: GM plays essential roles in soyasaponin's preventive bioactivities against steatohepatitis in MCD diet-induced NASH mice.

Targeting nonalcoholic fatty liver disease via gut microbiome-centered therapies.

Humans possess abundant amounts of microorganisms, including bacteria, fungi, viruses, and archaea, in their gut. Patients with nonalcoholic fatty liver disease (NAFLD) exhibit alterations in their gut microbiome and an impaired gut barrier function. Preclinical studies emphasize the significance of the gut microbiome in the pathogenesis of NAFLD. In this overview, we explore how adjusting the gut microbiome could serve as an innovative therapeutic strategy for NAFLD. We provide a summary of current information on untargeted techniques such as probiotics and fecal microbiota transplantation, as well as targeted microbiome-focused therapies including engineered bacteria, prebiotics, postbiotics, and phages for the treatment of NAFLD.

Integrated analysis of the transcriptome and its interaction with the metabolome in metabolic associated fatty liver disease: Gut microbiome signatures, correlation networks, and effect of PNPLA3 genotype.

Interactions between communities of the gut microbiome and with the host could affect the onset and progression of metabolic associated fatty liver disease (MAFLD), and can be useful as new diagnostic and prognostic biomarkers. In this study, we performed a multi-omics approach to unravel gut microbiome signatures from 32 biopsy-proven patients (10 simple steatosis -SS- and 22 steatohepatitis -SH-) and 19 healthy volunteers (HV). Human and microbial transcripts were differentially identified between groups (MAFLD vs. HV/SH vs. SS), and analyzed for weighted correlation networks together with previously detected metabolites from the same set of samples. We observed that expression of Desulfobacteraceae bacterium, methanogenic archaea, Mushu phage, opportunistic pathogenic fungi Fusarium proliferatum and Candida sorbophila, protozoa Blastocystis spp. and Fonticula alba were upregulated in MAFLD and SH. Desulfobacteraceae bacterium and Mushu phage were hub species in the onset of MAFLD, whereas the activity of Fonticula alba, Faecalibacterium prausnitzii, and Mushu phage act as key regulators of the progression to SH. A combination of clinical, metabolomic, and transcriptomic parameters showed the highest predictive capacity for MAFLD and SH (AUC = 0.96). In conclusion, faecal microbiome markers from several community members contribute to the switch in signatures characteristic of MAFLD and its progression towards SH.

Gut Microbiota and Plasma Bile Acids Associated with Non-Alcoholic Fatty Liver Disease Resolution in Bariatric Surgery Patients.

Bariatric surgery (BS) has several benefits, including resolution of non-alcoholic fatty liver disease (NAFLD) in many patients. However, a significant percentage of patients do not experience improvement in fatty liver after BS, and more than 10% develop new or worsening NAFLD features. Therefore, a question that remains unanswered is why some patients experience resolved NAFLD after BS and others do not. In this study, we investigated the fecal microbiota and plasma bile acids associated with NAFLD resolution in twelve morbidly obese patients undergoing BS, of whom six resolved their steatosis one year after surgery and another six did not. Results indicate that the hallmark of the gut microbiota in responder patients is a greater abundance of Bacteroides, Akkermansia, and several species of the Clostridia class (genera: Blautia, Faecalibacterium, Roseburia, Butyricicoccusa, and Clostridium), along with a decreased abundance of Actinomycetes/Bifidobacterium and Faecalicatena. NAFLD resolution was also associated with a sustained increase in primary bile acids (particularly non-conjugated), which likely results from a reduction in bacterial gut species capable of generating secondary bile acids. We conclude that there are specific changes in gut microbiota and plasma bile acids that could contribute to resolving NAFLD in BS patients. The knowledge acquired can help to design interventions with prebiotics and/or probiotics to promote a gut microbiome that favors NAFLD resolution.

Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis.

To evaluate the changes in the gut microbiota associated with changes in the biochemical markers of nonalcoholic fatty liver disease (NAFLD) after a lifestyle intervention with the Mediterranean diet. Participants (n = 297) from two centers of PREDIMED-Plus trial (Prevención con Dieta Mediterránea) were divided into three different groups based on the change tertile in the Hepatic Steatosis Index (HSI) or the Fibrosis-4 score (FIB-4) between baseline and one year of intervention. One-year changes in HSI were: tertile 1 (T1) (-24.9 to -7.51), T2 (-7.5 to -1.86), T3 (-1.85 to 13.64). The most significant differences in gut microbiota within the year of intervention were observed in the T1 and T3. According to the FIB-4, participants were categorized in non-suspected fibrosis (NSF) and with indeterminate or suspected fibrosis (SF). NSF participants showed higher abundances of Alcaligenaceae, Bacteroidaceae, Bifidobacteriaceae, Clostridiaceae, Enterobacteriaceae, Peptostreptococcaceae, Verrucomicrobiaceae compared to those with SF. Then, participants were divided depending on the FIB-4 tertile of change: T1 (-89.60 to -5.57), T2 (-5.56 to 11.4), and T3 (11.41 to 206.24). FIB-4 T1 showed a decrease in Akkermansia and an increase in Desulfovibrio. T2 had an increase in Victivallaceae, Clostridiaceae, and Desulfovibrio. T3 showed a decrease in Enterobacteriaceae, and an increase in Sutterella, Faecalibacterium, and Blautia. A relation between biochemical index changes of NAFLD/NASH (HSI and FIB-4) and gut microbiota changes were found. These observations highlight the importance of lifestyle intervention in the modulation of gut microbiota and the management of metabolic syndrome and its hepatic manifestations.

What You Need to KnowWhat is the context:Obesity and metabolic syndrome have been associated with nonalcoholic fatty liver disease (NAFLD). Gut microbiota and its interaction with the environment may play a key role in NAFLD.What is new:Mediterranean diet and physical activity can modify the scores for liver steatosis (HSI) and liver fibrosis (FIB−4) in only one year. A relation between the changes in these scores and gut microbiota changes was found.What is the impact:The discovery of microbiota-based biomarkers for NAFLD and the development of strategies to modulate gut microbiota in the treatment of NAFLD.

Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid.

Non-alcoholic steatohepatitis (NASH) is the severe form of non-alcoholic fatty liver disease, and is characterized by liver inflammation and fat accumulation. Dietary interventions, such as fibre, have been shown to alleviate this metabolic disorder in mice via the gut microbiota. Here, we investigated the mechanistic role of the gut microbiota in ameliorating NASH via dietary fibre in mice. Soluble fibre inulin was found to be more effective than insoluble fibre cellulose to suppress NASH progression in mice, as shown by reduced hepatic steatosis, necro-inflammation, ballooning and fibrosis. We employed stable isotope probing to trace the incorporation of 13C-inulin into gut bacterial genomes and metabolites during NASH progression. Shotgun metagenome sequencing revealed that the commensal Parabacteroides distasonis was enriched by 13C-inulin. Integration of 13C-inulin metagenomes and metabolomes suggested that P. distasonis used inulin to produce pentadecanoic acid, an odd-chain fatty acid, which was confirmed in vitro and in germ-free mice. P. distasonis or pentadecanoic acid was protective against NASH in mice. Mechanistically, inulin, P. distasonis or pentadecanoic acid restored gut barrier function in NASH models, which reduced serum lipopolysaccharide and liver pro-inflammatory cytokine expression. Overall this shows that gut microbiota members can use dietary fibre to generate beneficial metabolites to suppress metabolic disease.

Transgenic mice lacking FGF15/19-SHP phosphorylation display altered bile acids and gut bacteria, promoting nonalcoholic fatty liver disease.

Dysregulated bile acid (BA)/lipid metabolism and gut bacteria dysbiosis are tightly associated with the development of obesity and non-alcoholic fatty liver disease (NAFLD). The orphan nuclear receptor, Small Heterodimer Partner (SHP/NR0B2), is a key regulator of BA/lipid metabolism, and its gene-regulating function is markedly enhanced by phosphorylation at Thr-58 mediated by a gut hormone, fibroblast growth factor-15/19 (FGF15/19). To investigate the role of this phosphorylation in whole-body energy metabolism, we generated transgenic SHP-T58A knock-in mice. Compared with wild-type (WT) mice, the phosphorylation-defective SHP-T58A mice gained weight more rapidly with decreased energy expenditure and increased lipid/BA levels. This obesity-prone phenotype was associated with the upregulation of lipid/BA synthesis genes and downregulation of lipophagy/ß-oxidation genes. Mechanistically, defective SHP phosphorylation selectively impaired its interaction with LRH-1, resulting in de-repression of SHP/LRH-1 target BA/lipid synthesis genes. Remarkably, BA composition and selective gut bacteria which are known to impact obesity, were also altered in these mice. Upon feeding a high-fat diet, fatty liver developed more severely in SHP-T58A mice compared to WT mice. Treatment with antibiotics substantially improved the fatty liver phenotypes in both groups but had greater effects in the T58A mice so that the difference between the groups was largely eliminated. These results demonstrate that defective phosphorylation at a single nuclear receptor residue can impact whole-body energy metabolism by altering BA/lipid metabolism and gut bacteria, promoting complex metabolic disorders like NAFLD. Since posttranslational modifications generally act in gene- and context-specific manners, the FGF15/19-SHP phosphorylation axis may allow more targeted therapy for NAFLD.

Assessment of Nonalcoholic Fatty Liver Disease Symptoms and Gut-Liver Axis Status in Zebrafish after Exposure to Polystyrene Microplastics and Oxytetracycline, Alone and in Combination.

BACKGROUND: Environmental pollution may give rise to the incidence and progression of nonalcoholic fatty liver disease (NAFLD), the most common cause for chronic severe liver lesions. Although knowledge of NAFLD pathogenesis is particularly important for the development of effective prevention, the relationship between NAFLD occurrence and exposure to emerging pollutants, such as microplastics (MPs) and antibiotic residues, awaits assessment. OBJECTIVES: This study aimed to evaluate the toxicity of MPs and antibiotic residues related to NAFLD occurrence using the zebrafish model species. METHODS: Taking common polystyrene MPs and oxytetracycline (OTC) as representatives, typical NAFLD symptoms, including lipid accumulation, liver inflammation, and hepatic oxidative stress, were screened after 28-d exposure to environmentally realistic concentrations of MPs (0.69mg/L) and antibiotic residue (3.00µg/L). The impacts of MPs and OTC on gut health, the gut-liver axis, and hepatic lipid metabolism were also investigated to reveal potential affecting mechanisms underpinning the NAFLD symptoms observed. RESULTS: Compared with the control fish, zebrafish exposed to MPs and OTC exhibited significantly higher levels of lipid accumulation, triglycerides, and cholesterol contents, as well as inflammation, in conjunction with oxidative stress in their livers. In addition, a markedly smaller proportion of Proteobacteria and higher ratios of Firmicutes/Bacteroidetes were detected by microbiome analysis of gut contents in treated samples. After the exposures, the zebrafish also experienced intestinal oxidative injury and yielded significantly fewer numbers of goblet cells. Markedly higher levels of the intestinal bacteria-sourced endotoxin lipopolysaccharide (LPS) were also detected in serum. Animals treated with MPs and OTC exhibited higher expression levels of LPS binding receptor (LBP) and downstream inflammation-related genes while also exhibiting lower activity and gene expression of lipase. Furthermore, MP-OTC coexposure generally exerted more severe effects compared with single MP or OTC exposure. DISCUSSION: Our results suggested that exposure to MPs and OTC may disrupt the gut-liver axis and be associated with NAFLD occurrence. https://doi.org/10.1289/EHP11600.

Ecological shifts of salivary microbiota associated with metabolic-associated fatty liver disease.

Introduction: Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease related to metabolic syndrome. However, ecological shifts in the saliva microbiome in patients with MAFLD remain unknown. This study aimed to investigate the changes to the salivary microbial community in patients with MAFLD and explore the potential function of microbiota. Methods: Salivary microbiomes from ten MAFLD patients and ten healthy participants were analyzed by 16S rRNA amplicon sequencing and bioinformatics analysis. Body composition, plasma enzymes, hormones, and blood lipid profiles were assessed with physical examinations and laboratory tests. Results: The salivary microbiome of MAFLD patients was characterized by increased α-diversity and distinct ß-diversity clustering compared with control subjects. Linear discriminant analysis effect size analysis showed a total of 44 taxa significantly differed between the two groups. Genera Neisseria, Filifactor, and Capnocytophaga were identified as differentially enriched genera for comparison of the two groups. Co-occurrence networks suggested that the salivary microbiota from MAFLD patients exhibited more intricate and robust interrelationships. The diagnostic model based on the salivary microbiome achieved a good diagnostic power with an area under the curve of 0.82(95% CI: 0.61-1). Redundancy analysis and spearman correlation analysis revealed that clinical variables related to insulin resistance and obesity were strongly associated with the microbial community. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to metabolism were more prevalent in the two groups. Conclusions: Patients with MAFLD manifested ecological shifts in the salivary microbiome, and the saliva microbiome-based diagnostic model provides a promising approach for auxiliary MAFLD diagnosis.

Gut Microbiota in Non-Alcoholic Fatty Liver Disease Patients with Inflammatory Bowel Diseases: A Complex Interplay.

The intestinal microbiota represents the microbial community that colonizes the gastrointestinal tract and constitutes the most complex ecosystem present in nature. The main intestinal microbial phyla are Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucromicrobia, with a clear predominance of the two phyla Firmicutes and Bacteroidetes which account for about 90% of the intestinal phyla. Intestinal microbiota alteration, or dysbiosis, has been proven to be involved in the development of various syndromes, such as non-alcoholic fatty liver disease, Crohn's disease, and ulcerative colitis. The present review underlines the most recurrent changes in the intestinal microbiota of patients with NAFLD, Crohn's disease, and ulcerative colitis.

Interplay of Lymphocytes with the Intestinal Microbiota in Children with Nonalcoholic Fatty Liver Disease.

Abnormally high lymphocyte counts are seen in persons with nonalcoholic fatty liver disease (NAFLD). Gut microbiota dysbiosis is a risk factor for NAFLD. We assessed the gut microbiota of 63 healthy children and 63 children with NAFLD using 16S rRNA gene and metagenomic sequencing to explore the relationships. Compared with healthy children (HC group), the Bacteroidetes, Verrucomicrobia, and Akkermansia were less abundant, while the Actinobacteria were more abundant in children with NAFLD (FLD group). To understand the effect of lymphocytes on the gut microbiota of children with NAFLD, we compared the microbiota of 41 children with NAFLD and high numbers of lymphocytes (FLD_HL group) and 22 children with NAFLD and low numbers of lymphocytes (FLD_LL group). The abundances of Bacteroidetes, Verrucobacterium, and Akkermansia increased and Actinobacteria decreased in the FLD_LL group compared to the FLD_HL group. Akkermansia was negatively correlated with lymphocyte count. NAFLD may disturb the gut microbiota in children through reducing the abundance of Akkermansia and increasing the abundance of proinflammatory bacteria, such as Escherichia-Shigella. Conclusions: High lymphocyte counts are associated with disturbances of gut microbiota and emergence of opportunistic pathogens in children with NAFLD.

Gut bacteria alleviate smoking-related NASH by degrading gut nicotine.

Tobacco smoking is positively correlated with non-alcoholic fatty liver disease (NAFLD)1-5, but the underlying mechanism for this association is unclear. Here we report that nicotine accumulates in the intestine during tobacco smoking and activates intestinal AMPKα. We identify the gut bacterium Bacteroides xylanisolvens as an effective nicotine degrader. Colonization of B. xylanisolvens reduces intestinal nicotine concentrations in nicotine-exposed mice, and it improves nicotine-exacerbated NAFLD progression. Mechanistically, AMPKα promotes the phosphorylation of sphingomyelin phosphodiesterase 3 (SMPD3), stabilizing the latter and therefore increasing intestinal ceramide formation, which contributes to NAFLD progression to non-alcoholic steatohepatitis (NASH). Our results establish a role for intestinal nicotine accumulation in NAFLD progression and reveal an endogenous bacterium in the human intestine with the ability to metabolize nicotine. These findings suggest a possible route to reduce tobacco smoking-exacerbated NAFLD progression.

Gut microbiome and non-alcoholic fatty liver disease.

The human gastrointestinal tract (GIT) contains a dynamic and diverse collection of bacteria, archaea, and fungi termed the "gut microbiome." The gut microbiome has a major impact on the host during homeostasis and disease. The connection between both the host and the microbiome is complex, although its manipulation may assist prevent or treating a multitude of morbidities. These microorganisms play a critical role in the host's energy metabolism and homeostasis. According to new research, the microbes in the gastrointestinal tract play a substantial role in host health, and alterations in its composition and function might lead to the emergence of metabolic disorders like non-alcoholic fatty liver disease (NAFLD). The resilience of the GIT microbial ecology and its tolerance to perturbation are robust but not ideal. Several factors may disrupt the GIT microbiome's homeostasis leading to dysbiosis, characterized by an imbalanced equilibrium and perturbations in gut homeostasis. Irritable bowel disease (IBD), malnutrition, and metabolic disorders, such as NAFLD, have been associated with the dysbiotic gut microbiome. Recent evidence suggests that utilizing medications, prebiotics, probiotics, and fecal microbiota transplantation (FMT) to manipulate the microbiome could be a viable method for treating NAFLD.

Gut Microbiota-A Future Therapeutic Target for People with Non-Alcoholic Fatty Liver Disease: A Systematic Review.

Non-alcoholic fatty liver disease (NAFLD) represents an increasing cause of liver disease, affecting one-third of the population worldwide. Despite many medications being in the pipeline to treat the condition, there is still no pharmaceutical agent licensed to treat the disease. As intestinal bacteria play a crucial role in the pathogenesis and progression of liver damage in patients with NAFLD, it has been suggested that manipulating the microbiome may represent a therapeutical option. In this review, we summarise the latest evidence supporting the manipulation of the intestinal microbiome as a potential therapy for treating liver disease in patients with NAFLD.

Alteration of the gut microbiota's composition and metabolic output correlates with COVID-19-like severity in obese NASH hamsters.

Obese patientss with nonalcoholic steatohepatitis (NASH) are particularly prone to developing severe forms of coronavirus disease 19 (COVID-19). The gut-to-lung axis is critical during viral infections of the respiratory tract, and a change in the gut microbiota's composition might have a critical role in disease severity. Here, we investigated the consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the gut microbiota in the context of obesity and NASH. To this end, we set up a nutritional model of obesity with dyslipidemia and NASH in the golden hamster, a relevant preclinical model of COVID-19. Relative to lean non-NASH controls, obese NASH hamsters develop severe inflammation of the lungs and liver. 16S rRNA gene profiling showed that depending on the diet, SARS-CoV-2 infection induced various changes in the gut microbiota's composition. Changes were more prominent and transient at day 4 post-infection in lean animals, alterations still persisted at day 10 in obese NASH animals. A targeted, quantitative metabolomic analysis revealed changes in the gut microbiota's metabolic output, some of which were diet-specific and regulated over time. Our results showed that specifically diet-associated taxa are correlated with disease parameters. Correlations between infection variables and diet-associated taxa highlighted a number of potentially protective or harmful bacteria in SARS-CoV-2-infected hamsters. In particular, some taxa in obese NASH hamsters (e.g. Blautia and Peptococcus) were associated with pro-inflammatory parameters in both the lungs and the liver. These taxon profiles and their association with specific disease markers suggest that microbial patterns might influence COVID-19 outcomes.

Extraction, purification, structural characterization, and gut microbiota relationship of polysaccharides: A review.

Intestinal dysbiosis is one of the major causes of the occurrence of metabolic syndromes, such as obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Polysaccharide-based microbial therapeutic strategies have excellent potential in the treatment of metabolic syndromes, but the underlying regulatory mechanisms remain elusive. Identification of the internal regulatory mechanism of the gut microbiome and the interaction mechanisms involving bacteria and the host are essential to achieve precise control of the gut microbiome and obtain valuable clinical data. Polysaccharides cannot be directly digested; the behavior in the intestinal tract is considered a "bridge" between microbiota and host communication. To provide a relatively comprehensive reference for researchers in the field, we will discuss the polysaccharide extraction and purification processes and chemical and structural characteristics, focusing on the polysaccharides in gut microbiota through the immune system, gut-liver axis, gut-brain axis, energy axis interactions, and potential applications.

Longitudinal 16S rRNA Sequencing Reveals Relationships among Alterations of Gut Microbiota and Nonalcoholic Fatty Liver Disease Progression in Mice.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent and progressive disease spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), yet there is no effective treatment and efficient noninvasive diagnostic method for NASH. The present study investigated the longitudinal alternations of gut microbiota in the Western diet (WD) induced murine NAFLD model using 16S rRNA sequencing. Evident steatosis and inflammation were detected in the liver at the 8th and 12th week, while prompted hepatic oxidative injury and fibrosis were found at the 16th week. In this progressive process, impaired bile acid (BA) metabolism plays a vital part. Long-term WD intervention alters microbial richness and composition in the intestine, shaping characteristic microbial feature correspondence to each NAFLD stage. Descending abundances of Clostridia and Ruminococcaceae were found in NAFLD progression, while inflammation-related microbes [Eubacterium]_fissicatena_group, Romboutsia, and Erysipelatoclostridium were verified to identify borderline NASH at 8th and 12th week, and BA-associated taxa Dubosiella, Bosea, Helicobacter, and Alistipes were recognized as special symbols reflecting the state of oxidative damage and fibrosis in NASH at 16th week. Further, feces and colon abundances of Akkermansia were verified to be depleted in the process of borderline NASH progressed to NASH, and exhibited substantial correlations with NAFLD indexes ALT, AST, TC, and TBA. These characteristic taxa were effective to identify NAFLD and NASH, and microbiota-derived predictive models for NAFLD and NASH exhibited great potential (AUC 0.983 and 0.784). These findings demonstrate that a core set of gut microbiome especially BA-related taxa may be adopted as a noninvasive diagnostic tool for NAFLD and NASH. IMPORTANCE This study concentrates on longitudinal alternations of gut microbiota in NAFLD progression and discovers the interrelationships between them. These findings may uncover the role of gut microbiota in NAFLD progression and identify novel noninvasive diagnostic tools for NAFLD based on microbial biomarkers.

The Microbiota and It's Correlation With Metabolites in the Gut of Mice With Nonalcoholic Fatty Liver Disease.

In recent years, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease in the world. As an important model animal, the characteristics of gut microbiota alteration in mice with NAFLD have been studied but the changes in metabolite abundance in NAFLD mice and how the gut microbiota affects these intestinal metabolites remain unclear. In this experiment, a mouse model for NAFLD was established by a high-fat diet. The use of 16S rDNA technology showed that while there were no significant changes in the alpha diversity in the cecum of NAFLD mice, the beta diversity changed significantly. The abundance of Blautia, Unidentified-Lachnospiraceae, Romboutsia, Faecalibaculum, and Ileibacterium increased significantly in NAFLD mice, while Allobaculum and Enterorhabdus decreased significantly. Amino acids, lipids, bile acids and nucleotide metabolites were among the 167 significantly different metabolites selected. The metabolic pathways of amino acids, SFAs, and bile acids were significantly enhanced, while the metabolic pathways of PUFAs, vitamins, and nucleotides were significantly inhibited. Through correlation and MIMOSA2 analysis, it is suggested that gut microbiota does not affect the changes of lipids and bile acids but can reduce thiamine, pyridoxine, and promote L-phenylalanine and tyramine production. The findings of this study will help us to better understand the relationship between gut microbiota and metabolites in NAFLD.