Bifidobacteria and lactobacilli in the gut microbiome of children with non-alcoholic fatty liver disease: which strains act as health players?

Non-alcoholic fatty liver disease (NAFLD) has been linked to altered gut microbiome; however, evidence from large population-based studies is limited. We compared gut microbiome profiles of 188 male and 233 female NAFLD cases with 571 male and 567 female controls from two longitudinal studies of urban Chinese adults. History of NAFLD was assessed during surveys administered in 2004–2017. Microbiota were assessed using 16S rRNA sequencing of stool samples collected in 2015–2018. Associations of NAFLD with microbiome diversity and composition were evaluated by generalized linear or logistic regression models. Compared with controls, male cases had lower microbial α-diversity, higher abundance of genera Dialister and Streptococcus and Bifidobacterium species, lower abundance of genus Phascolarctobacterium, and lower prevalence of taxa including order RF39 (all p < 0.05). In contrast, female cases had higher α-diversity, higher abundance of genus Butyricimonas and a family of order Clostridiales, lower abundance of Dialister and Bifidobacterium species, and higher prevalence of RF39. Significant NAFLD–sex interactions were found for α-diversity and above taxa (all false discovery rate < 0.1). In conclusion, we observed sex-specific gut microbiome features related to history of NAFLD. Further studies are needed to validate our findings and evaluate the health effects of NAFLD-related gut microbiota.

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The role of the gut microbiome and diet in the pathogenesis of non-alcoholic fatty liver disease

Clinical and Molecular Hepatology ◽

10.3350/cmh.2020.0129 ◽

2021 ◽

Vol 27 (1) ◽

pp. 22-43

Author(s):

Erica Jennison ◽

Christopher D. Byrne

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Gut Microbiome ◽

Fatty Liver Disease ◽

Dietary Factors ◽

Current Evidence ◽

Alcoholic Fatty Liver ◽

Close Relationship ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, with a prevalence that is increasing in parallel with the global rise in obesity and type 2 diabetes mellitus. The pathogenesis of NAFLD is complex and multifactorial, involving environmental, genetic and metabolic factors. The role of the diet and the gut microbiome is gaining interest as a significant factor in NAFLD pathogenesis. Dietary factors induce alterations in the composition of the gut microbiome (dysbiosis), commonly reflected by a reduction of the beneficial species and an increase in pathogenic microbiota. Due to the close relationship between the gut and liver, altering the gut microbiome can affect liver functions; promoting hepatic steatosis and inflammation. This review summarises the current evidence supporting an association between NAFLD and the gut microbiome and dietary factors. The review also explores potential underlying mechanisms underpinning these associations and whether manipulation of the gut microbiome is a potential therapeutic strategy to prevent or treat NAFLD.

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The role of the gut microbiome and exercise in non-alcoholic fatty liver disease

Therapeutic Advances in Gastroenterology ◽

10.1177/1756284820941745 ◽

2020 ◽

Vol 13 ◽

pp. 175628482094174

Author(s):

Veera Houttu ◽

Ulrika Boulund ◽

Aldo Grefhorst ◽

Maarten R. Soeters ◽

Sara-Joan Pinto-Sietsma ◽

...

Keyword(s):

Clinical Trials ◽

Liver Disease ◽

Fatty Liver ◽

Gut Microbiome ◽

Fatty Liver Disease ◽

Inflammatory Responses ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

In recent years, the human gut microbiome has been found to influence a multitude of non-communicable diseases such as cardiovascular disease and metabolic syndrome, with its components type 2 diabetes mellitus and obesity. It is recognized to be mainly influenced by environmental factors, such as lifestyle, but also genetics may play a role. The interaction of gut microbiota and obesity has been widely studied, but in regard to non-alcoholic fatty liver disease (NAFLD) as a manifestation of obesity and insulin resistance, the causal role of the gut microbiome has not been fully established. The mechanisms by which the gut microbiome influences lipid accumulation, inflammatory responses, and occurrence of fibrosis in the liver are a topic of active research. In addition, the influence of exercise on gut microbiome composition is also being investigated. In clinical trials, exercise reduced hepatic steatosis independently of weight reduction. Other studies indicate that exercise may modulate the gut microbiome. This puts forward the question whether exercise could mediate its beneficial effects on NAFLD via changes in gut microbiome. Yet, the specific mechanisms underlying this potential connection are largely unknown. Thus, associative evidence from clinical trials, as well as mechanistic studies in vivo are called for to elucidate the relationship between exercise and the gut microbiome in NAFLD. Here, we review the current literature on exercise and the gut microbiome in NAFLD.

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Plasma and stool metabolomic biomarkers of non-alcoholic fatty liver disease in Argentina

10.1101/2020.07.30.20165308 ◽

2020 ◽

Author(s):

Flavia Noelia Mazzini ◽

Frank Cook ◽

John Gounarides ◽

Sebastian Marciano ◽

Leila Haddad ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Disease Progression ◽

Gut Microbiome ◽

Plasma Levels ◽

Fatty Liver Disease ◽

Study Groups ◽

Alcoholic Fatty Liver ◽

Number Of Patients ◽

Alcoholic Fatty Liver Disease

Background and Aims: Non-invasive biomarkers are urgently needed to identify patients with non-alcoholic fatty liver disease (NAFLD) especially those at risk of disease progression. This is particularly true in high prevalence areas such as Latin America. The gut microbiome and intestinal permeability may play a role in the risk of developing NAFLD and NASH, but the mechanism by which microbiota composition disruption (or dysbiosis) may affect NAFLD progression is still unknown. Targeted metabolomics is a powerful technology for discovering new associations between gut microbiome-derived metabolites and disease. Thus, we aimed to identify potential metabolomic biomarkers related to the NAFLD stage in Argentina, and to assess their relationship with clinical and host genetic factors. Materials and methods: Adult healthy volunteers (HV) and biopsy-proven simple steatosis (SS) or non-alcoholic steatohepatitis (NASH) patients were recruited. Demographic, clinical and food frequency consumption data, as well as plasma and stool samples were collected. SNP rs738409 (PNPLA3 gene) was determined in all volunteers. HPLC and flow injection analysis with MS/MS in tandem was applied for metabolomic studies using the MxP Quant 500 Kit (Biocrates Life Sciences AG, Austria). Significantly different metabolites among groups were identified with MetaboAnalyst v4.0. Bivariate and multivariate analyses were used to identify variables that were independently related to NAFLD stage. Forward stepwise logistic regression models were constructed to design the best feature combination that could distinguish between study groups. Receiver Operating Characteristic (ROC) curves were used to evaluate models′ accuracy. Results: A total of 53 volunteers were recruited: 19 HV, 12 SS and 22 NASH. Diet was similar between groups. The concentration of 33 out of 424 detected metabolites (25 in plasma and 8 in stool) was significantly different among study groups. Levels of triglycerides (TG) were higher among NAFLD patients, whereas levels of phosphatidylcholines (PC) and lysoPC were depleted relative to HV. The PNPLA3 risk genotype for NAFLD and NASH (GG) was related to higher plasma levels of eicosenoic acid FA(20:1) (p<0.001). Plasma metabolites showed a higher accuracy for diagnosis of NAFLD and NASH when compared to stool metabolites. Body mass index (BMI) and plasma levels of PC aa C24:0, FA(20:1) and TG(16:1_34:1) showed high accuracy for diagnosis of NAFLD; whereas the best AUROC for discriminating NASH from SS was that of plasma levels of PC aa C24:0 and PC ae C40:1. Conclusion: A panel of plasma and stool biomarkers could distinguish between NAFLD and NASH in a cohort of patients from Argentina. Plasma biomarkers may be diagnostic in these patients and could be used to assess disease progression. Further validation studies including a larger number of patients are needed.

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Lactobacillus lactis and Pediococcus pentosaceus ‐driven reprogramming of gut microbiome and metabolome ameliorates the progression of non‐alcoholic fatty liver disease

Clinical and Translational Medicine ◽

10.1002/ctm2.634 ◽

2021 ◽

Vol 11 (12) ◽

Author(s):

Jeong Seok Yu ◽

Gi Soo Youn ◽

Jieun Choi ◽

Chang‐Ho Kim ◽

Byung Yong Kim ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Gut Microbiome ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Pediococcus Pentosaceus ◽

Lactobacillus Lactis ◽

Alcoholic Fatty Liver Disease

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Gut Microbiome-Mediated Alteration of Immunity, Inflammation, and Metabolism Involved in the Regulation of Non-alcoholic Fatty Liver Disease

Frontiers in Microbiology ◽

10.3389/fmicb.2021.761836 ◽

2021 ◽

Vol 12 ◽

Author(s):

Li-Hong He ◽

Dun-Han Yao ◽

Ling-Yun Wang ◽

Lei Zhang ◽

Xue-Li Bai

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Gut Microbiome ◽

Fatty Liver Disease ◽

Diagnosis And Treatment ◽

Gastrointestinal Microbiome ◽

Alcoholic Fatty Liver ◽

Public Health Burden ◽

Inflammatory Status ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of end-stage liver disease, leading to a rapidly growing global public health burden. The term “gut microbiome (GM)” refers to the approximately 100 trillion microbial cells that inhabit the host’s gastrointestinal tract. There is increasing evidence that GM is involved in the pathogenesis of NAFLD and may be a potential target for intervention. To explore GM-based strategies for precise diagnosis and treatment of NAFLD, great efforts have been made to develop a comprehensive and in-depth understanding of the host–microbe interaction. This review evaluates this interaction critically, mainly considering the intricate regulation of the metabolism, immunity, and inflammatory status during the evolution of the disease pathogenesis, revealing roles for the GM in NAFLD by examining advances in potential mechanisms, diagnostics, and modulation strategies.Synopsis: Considering the intricate metabolic and immune/inflammatory homeostasis regulation, we evaluate the latest understanding of the host–microbe interaction and reveal roles for the gastrointestinal microbiome in NAFLD. Strategies targeting the gastrointestinal microbiome for the diagnosis and treatment of NAFLD are proposed.

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Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives

Biomolecules ◽

10.3390/biom12010056 ◽

2021 ◽

Vol 12 (1) ◽

pp. 56

Author(s):

Natalia Vallianou ◽

Gerasimos Socrates Christodoulatos ◽

Irene Karampela ◽

Dimitrios Tsilingiris ◽

Faidon Magkos ◽

...

Keyword(s):

Liver Disease ◽

Gut Microbiota ◽

Fatty Liver ◽

Gut Microbiome ◽

Fatty Liver Disease ◽

Microbial Metabolites ◽

Alcoholic Fatty Liver ◽

Gut Dysbiosis ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. NAFLD begins as a relatively benign hepatic steatosis which can evolve to non-alcoholic steatohepatitis (NASH); the risk of cirrhosis and hepatocellular carcinoma (HCC) increases when fibrosis is present. NAFLD represents a complex process implicating numerous factors—genetic, metabolic, and dietary—intertwined in a multi-hit etiopathogenetic model. Recent data have highlighted the role of gut dysbiosis, which may render the bowel more permeable, leading to increased free fatty acid absorption, bacterial migration, and a parallel release of toxic bacterial products, lipopolysaccharide (LPS), and proinflammatory cytokines that initiate and sustain inflammation. Although gut dysbiosis is present in each disease stage, there is currently no single microbial signature to distinguish or predict which patients will evolve from NAFLD to NASH and HCC. Using 16S rRNA sequencing, the majority of patients with NAFLD/NASH exhibit increased numbers of Bacteroidetes and differences in the presence of Firmicutes, resulting in a decreased F/B ratio in most studies. They also present an increased proportion of species belonging to Clostridium, Anaerobacter, Streptococcus, Escherichia, and Lactobacillus, whereas Oscillibacter, Flavonifaractor, Odoribacter, and Alistipes spp. are less prominent. In comparison to healthy controls, patients with NASH show a higher abundance of Proteobacteria, Enterobacteriaceae, and Escherichia spp., while Faecalibacterium prausnitzii and Akkermansia muciniphila are diminished. Children with NAFLD/NASH have a decreased proportion of Oscillospira spp. accompanied by an elevated proportion of Dorea, Blautia, Prevotella copri, and Ruminococcus spp. Gut microbiota composition may vary between population groups and different stages of NAFLD, making any conclusive or causative claims about gut microbiota profiles in NAFLD patients challenging. Moreover, various metabolites may be involved in the pathogenesis of NAFLD, such as short-chain fatty acids, lipopolysaccharide, bile acids, choline and trimethylamine-N-oxide, and ammonia. In this review, we summarize the role of the gut microbiome and metabolites in NAFLD pathogenesis, and we discuss potential preventive and therapeutic interventions related to the gut microbiome, such as the administration of probiotics, prebiotics, synbiotics, antibiotics, and bacteriophages, as well as the contribution of bariatric surgery and fecal microbiota transplantation in the therapeutic armamentarium against NAFLD. Larger and longer-term prospective studies, including well-defined cohorts as well as a multi-omics approach, are required to better identify the associations between the gut microbiome, microbial metabolites, and NAFLD occurrence and progression.

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