Role of the gut microbiota in nonalcoholic fatty liver disease, the ability of equol produce and Helicobacter pylori infection

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. Previous studies on the association between Helicobacter pylori (HP) infection and NAFLD are inconsistent. Our study was aimed to find out the relationship between HP infection and NAFLD. We performed a large cross-sectional study in northern Chinese adults in 2015. 13C-urea breath tests were used to determine HP infection status. Abdominal ultrasonography was performed to diagnose NAFLD. Multivariable logistic regression was conducted to identify the association between HP infection and NAFLD. A total of 4081 individuals were included in this study; 2137 (52.36%) participants were HP-positive, and 1022 (47.82%) were diagnosed with NAFLD in HP-positive individuals. The odds ratios (OR) and 95% confidence intervals (CI) of participants with HP infection for NAFLD were 1.20 (1.06–1.36) in crude model and 1.27 (1.07–1.50) in fully adjusted model. When stratified by sex and dyslipidemia, the fully adjusted OR and 95% CI for NAFLD were 1.22 (1.10–1.80) in females and 1.44 (1.18–1.75) in subjects with dyslipidemia. There were not significant increased OR for NAFLD when stratified by age. The study indicate that HP infection is associated with NAFLD, particularly in females and patients with dyslipidemia, suggesting that HP eradication might be an alternative method for the prevention or treatment of NAFLD treatment.

Introduction:Helicobacter pylori (H. pylori) infection is postulated to predispose Non Alcoholic Fatty Liver Disease (NAFLD) through alteration of lipid profile, reduction of adiponectin, insulin resistance, etc. In the setting of increased incidence of NAFLD, the possible therapeutic and preventive implications of an association of H. pylori infection with NAFLD holds interest. Aim: To determine the prevalence of H. pylori infection among NAFLD patients and its association with severity of NAFLD. Materials and Methods: This hospital based cross-sectional study was carried out during July 2019 to December 2021 among 197 patients diagnosed with NAFLD. H. pylori infection was diagnosed by H. pylori specific anti-Immunoglobulin M (IgM) and anti-IgG antibody tests. Descriptive statistics like proportions, mean and standard deviation were used. Chisquare test was used to check for associations of disease severity with H. pylori infection. Results: The study population included 90 females and 107 males. A total of 121 (61.4%) subjects had grade 1 fatty liver, while 46 (23.4%) had grade 2 fatty liver and 30 (15.2%) had grade 3 fatty liver. A total of 125 (63.45%) were H. pylori IgG positive. H. pylori infection positively associated with disease grade, Chronic Liver Disease (CLD) and decompensation (p-value <0.001). Conclusion: The prevalence of H. pylori infection in patients with NAFLD was 63.45% and H. pylori seropositivity was significantly associated with disease severity.

Helicobacter pylori (HP) infection is known to be a significant risk factor in the development of certain gastric conditions, such as ulcers, gastritis, and malignancy. Recently, however, the systemic effect of HP infection on other organ systems has come to be appreciated. In this review, we will explore the association between HP infection and nonalcoholic fatty liver disease (NAFLD), the hepatic component of metabolic syndrome. The possible association between HP infection and NAFLD initially stemmed from the isolation of HP bacteria in the livers of patients with NAFLD. Although there have been conflicting results, several subsequent clinical trials have demonstrated a higher rate of fatty liver and NASH in HP-positive patients compared to HP-negative patients; in addition, small trials examining the effect of HP eradication have shown improvement in markers of NAFLD activity, further supporting a link between these two conditions. The pathophysiology behind the possible association between HP infection and NAFLD has yet to be fully elucidated; several possible mechanisms include induction of a pro-inflammatory state that shifts the body toward a more lipogenic profile, and a hormonal shift that favors progression toward insulin resistance and fibrosis. The association between HP infection and NAFLD has been demonstrated in several clinical trials, including small trials evaluating the effect of HP eradication on NAFLD. Future studies examining the pathophysiology behind this association are the next step in characterizing the relationship between these two conditions.

Objective To investigate the association between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD). Methods Data from 2051 participants who underwent 13C urea breath test and abdominal ultrasound examinations was collected. Participants were allocated to NAFLD risk group and NAFLD nonrisk group based on definite risk factors for NAFLD. The relationship between H. pylori infection and NAFLD was analyzed. Results No significant difference was found between rates of H. pylori infection and NAFLD using the chi-square test (P = 0.30) or regression analysis (P = 0.70). There was no significant difference between rates of H. pylori infection with and without NAFLD (P = 0.47) in the NAFLD risk group or in the NAFLD nonrisk group (P = 0.59). There was no significant difference between rates of H. pylori infection in men (P = 0.69) and in women (P = 0.27) or in participants aged 18–40 years (P = 0.43), 41–65 years (P = 0.14), and ≥66 years (P = 0.66) with and without NAFLD in the NAFLD risk group or between the same sex or age groups (P = 0.82, P = 0.66, P = 0.24, P = 0.53, and P = 1.00, resp.) in the NAFLD nonrisk group. Conclusions H. pylori infection does not appear to increase the NAFLD prevalence rate or to be associated with, or a risk factor for, NAFLD.

LINKED CONTENTThis article is linked to Wijarnpreecha et al paper. To view this article, visit https://doi.org/10.1111/apt.17424.

To investigate the correlation between Helicobacter pylori (H. Pylori) infection and polymorphism of adiponectin gene promoter -11391G/A, extracellular superoxide dismutase (EC-SOD) gene in nonalcoholic fatty liver disease (NAFLD). From June, 2010 to July, 2014, a hospital-based 1:1 matched case-control study was carried out, with 600 cases of NAFLD and 600 healthy people in the First Affiliated Hospital of Xinxiang Medical University. The genetic polymorphisms of adiponectin gene promoter -11391G/A and EC-SOD were analyzed by polymorphism-polymerase chain reaction (PCR) technique in peripheral blood leukocytes of the subjects. 14C-urea breath test (14C-UBT) was used to test 14C disntegration per minute (DPM) for evaluating the infections status of H. Pylori. The synergistic effect between the two mutants and the gene-environment interaction of the genotypes with H. Pylori infection were analyzed. The frequencies of -11391G/A (AA) and EC-SOD (CG+GG) were 50.67% and 50.33% in NAFLD cases, 23.83% and 24.17% in healthy controls, respectively. Statistical tests showed significantly higher frequencies of -11391G/A (AA) and EC-SOD (CG+GG) in the NAFLD group (-11391G/A: P=0.0051; EC-SOD: P=0.0057). The risk of NAFLD with -11391G/A (AA) was significantly higher than those with -11391G/A(GG+GA) (OR=3.2822, 95% CI 1.9170 to 5.2039). The individuals who carried EC-SOD (CG+GG) had a high risk of NAFLD (OR=3.1800, 95% CI 1.7974 to 5.2391). Combined analysis of the polymorphisms showed that percentage of -11391G/A (AA)/EC-SOD (CG+GG) in the NAFLD group was significantly higher than that in the control groups (25.50% vs 5.83%, P=0.0039). The people who carried with -11391G/A (AA)/EC-SOD (CG+GG) had a high risk of NAFLD (OR=10.3190, 95% CI 8.1869 to 20.5102). The H. Pylori infection rate in the NAFLD group was significantly higher than that in the control group (OR=3.1667, 95% CI 1.9139 to 5.7443, P=0.0062), and statistical analysis suggested a positive correlation between H. Pylori infection and NAFLD with -11391G/A (AA) and EC-SOD (CG+GG) (-11391G/A: γ=1.8532; EC-SOD: γ=1.7899). These carriers of -11391G/A(AA) and EC-SOD (CG+GG) genotypes may have a high risk of NAFLD, and the gene genotypes can interact with H. Pylori infection in the pathogenesis of NAFLD. Therefore, effective prevention measures for NAFLD should consider eradicating H. Pylori or regulating gene expression.

Helicobacter pylori infection has been investigated as a potential risk factor for non-alcoholic fatty liver disease (NAFLD). Some studies suggest a possible link between the two conditions. The purpose of this study is to study the relationship between H. pylori infection and NAFLD in pediatrics and its relation to NAFLD grades. A case–control study to identify predictors of NAFLD and a comparative cross-sectional approach to determine factors affecting NAFLD grades were adopted. One hundred NAFLD children (ultrasound-based) and a control group of 100 non-NAFLD children were recruited. Both groups were evaluated by detecting H. pylori stool antigen. Immunoglobulin G antibodies to Cag A (cytotoxin-associated gene A), Vac A (vacuolating cytotoxin A), Gro EL (chaperonin Gro EL), HCPC (Helicobacter cysteine-rich protein C), and Ure A (Urease subunit A) were assessed in the serum of those with positive stool antigen. H. pylori infection was significantly higher in NAFLD children compared to the control group (64% versus 25%, p-value < .001). (NAFLD children showed higher Cag A and Vac A positivity (34, 10%) versus (2%, 0%) in the control group, respectively, p-value < .001). The regression model showed that H. pylori positivity (OR (odds ratio) = 5.021, 95% CI (confidence interval): 1.105–22.815), homeostatic model assessment of insulin resistance (Homa IR) (OR = 18.840, 95% CI: 3.998–88.789), waist percentile (OR = 1.184, 95% CI: 1.044–1.344), and triglycerides (OR = 1.029, 95% CI: 1.012–1.047) were predictors for NAFLD. Cag A positivity (OR = 2.740, 95% CI: 1.013–7.411) was associated with higher NAFLD grade (grade 2 fatty liver).Conclusions:H. pylori infection could increase the risk of NAFLD in children. Triglycerides, waist circumference, and Homa IR are significant independent predictors of NAFLD.What is Known:• NAFLD has become one of the most common liver diseases among children because of the increased prevalence of pediatric obesity.• Dyslipidemia and insulin resistance play a central role in NAFLD pathogenesis. • NAFLD could be explained by the multiple-hit hypothesis. The gut microbiota is an important factor in this hypothesis (gut liver axis).What is New:• Helicobacter pylori infection could increase the risk of NAFLD in children. • H. pylori Cytotoxin-associated gene A (Cag A) positivity is associated with higher NAFLD grade.

Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) represent significant concerns in global health. However, the precise relationship between H. pylori and NAFLD remains a subject of ongoing debate. This study endeavors to elucidate the association between H. pylori infection and the susceptibility to NAFLD. Furthermore, we aim to investigate the interplay among H. pylori infection, NAFLD, and metabolic syndrome (MetS). We conducted an extensive search of the PubMed, EMBASE, and Web of Science databases spanning from inception to January 2024. Our examination focused on rigorous studies investigating the correlation between H. pylori infection and NAFLD. Utilizing a random-effects model, we computed the pooled odds ratio (OR) and corresponding 95% confidence interval (CI). Additionally, we assessed statistical heterogeneity, performed sensitivity analyses, and scrutinized the potential for publication bias. Thirty-four studies involving 175,575 individuals were included in our meta-analysis. Among these, 14 studies (involving 94,950 patients) demonstrated a higher incidence of NAFLD in H. pylori infection-positive individuals compared to H. pylori infection-negative individuals [RR = 1.17, 95% CI (1.10, 1.24), Z = 4.897, P < 0.001]. Seventeen studies (involving 74,928 patients) indicated a higher positive rate of H. pylori infection in patients with NAFLD compared to those without NAFLD [RR = 1.13, 95% CI (1.02, 1.24), Z = 2.395, P = 0.017]. Sensitivity analyses confirmed the robustness of these findings, and funnel plot analysis revealed no significant publication bias. Furthermore, we observed associations between H. pylori infection or NAFLD and various metabolic factors, including body mass index (BMI), blood pressure, lipids, liver function, and kidney function. Our meta-analysis presents evidence supporting a reciprocal relationship between H. pylori infection and the susceptibility to NAFLD. Nevertheless, additional investigations are warranted to bolster this correlation and unravel the underlying mechanisms involved.

Background: Both nonalcoholic fatty liver disease (NAFLD) and Helicobacter pylori (H. pylori) infection have high prevalence worldwide, and the relationship between both remains controversial. We try to investigate whether H. pylori infection is associated with NAFLD and increased liver fat deposition and stiffness in this cross-sectional study.Methods: The physical examination data of 5,665 subjects were obtained from February 2018 to June 2019 in this study. Clinical and biochemical data were collected. NAFLD was diagnosed using abdominal color Doppler ultrasonography. Liver steatosis and stiffness were understood by two parameters of transient elastography (TE): fat attenuation parameter (FAP) and liver stiffness measurement (LSM). H. pylori infection was determined using the 13C urea breath tests.Results: The total prevalence of NAFLD and H. pylori infection was 30.2 and 37.0%, respectively. In men, the prevalence of NAFLD and the levels of FAP and LSM in H. pylori-positive group were significantly higher than H. pylori-negative group (all p < 0.01), but no significant difference was found in women. In men, the infection rate of H. pylori in NAFLD group and LSM ≥ 7.4 kPa group was significantly higher than control group. Multivariate logistic regression analysis revealed that H. pylori infection was not independently associated with NAFLD and FAP ≥ 240 dB/m. However, H. pylori infection was associated with LSM ≥ 7.4 kPa in men.Conclusions: Our study suggests that H. pylori infection is not significantly associated with NAFLD and elevated liver steatosis, whereas it may be the risk factor of elevated liver stiffness in men.

Although clinical studies have shown the possible relationship between Helicobacter pylori (H. pylori) infection and the development of nonalcoholic fatty liver disease (NAFLD), their causal relationship is still unknown. This bidirectional Mendelian randomization (MR) study aimed to investigate the causal link between H. pylori infection and NAFLD. Two previously reported genetic variants SNPs rs10004195 and rs368433 were used as the instrumental variables (IVs) of H. pylori infection. The genetic variants of NAFLD were extracted from the largest genome-wide association study (GWAS) summary data with 1,483 cases and 17,781 controls. The exposure and outcome data were obtained from the publicly available GWAS dataset. Then, a bidirectional MR was carried out to evaluate the causal relationship between H. pylori infection and NAFLD. In addition, the GWAS data were also collected to explore the causal relationship between H. pylori infection and relevant clinical traits of NAFLD, including triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and body mass index (BMI). Genetically predicted H. pylori infection showed no association with NAFLD both in FinnGen GWAS (OR, 1.048; 95% CI, 0.778–1.411; value of p = 0.759) and the GWAS conducted by Anstee (OR, 0.775; 95% CI, 0.475–1.265; value of p = 0.308). An inverse MR showed no causal effect of NAFLD on H. pylori infection (OR,0.978;95% CI, 0.909–1.052; value of p = 0.543). No significant associations were observed between H. pylori infection and the levels of triglycerides, LDL-C, HDL-C, or FBG, while H. pylori infection was associated with an increase in BMI. These results indicated that there was no genetic evidence for a causal link between H. pylori and NAFLD, suggesting that the eradication or prevention of H. pylori infection might not benefit NAFLD and vice versa.

BackgroundSeveral studies have revealed a positive correlation between a Helicobacter pylori (HP) infection and the risk of non-alcoholic fatty liver disease (NAFLD). This meta-analysis was conducted to explore further the relationship between HP infection and NAFLD in the Asian and non-Asian populations.MethodsRelevant studies published from inception to July 22, 2021, in the following databases: PubMed, EMBASE, the Cochrane library, and Web of Science were comprehensively searched. The odds ratio (OR) and hazard ratio (HR) with a 95% confidence interval (95%CI) were pooled by the random-effects model or fixed-effects model. Additionally, subgroup and sensitivity analyses were performed. The funnel plot and the Egger test were used to estimate publication bias.ResultsThis meta-analysis included 25 studies involving 107,306 participants. Positive associations between HP infection and NAFLD were found both for the Asian (OR = 1.30, 95% CI: 1.13–1.49, P < 0.01; I2 = 94.30%, P < 0.01) and non-Asian populations (OR = 1.42, 95% CI: 1.04–1.94, P = 0.03; I2 = 44.90%, P = 0.09). Moreover, similar results were observed in the Asian female group (OR = 1.31, 95% CI: 1.17–1.46, P < 0.01; I2 = 46.30%, P = 0.07) but not for the Asian male group. Subgroup analyses for the Asian population showed that there were differences in the association among NAFLD diagnosis methods (P < 0.01) and the study design (P < 0.01). However, subgroup and sensitivity analyses results showed that the association for the non-Asian population was not stable enough.ConclusionsThe data obtained in this systematic review and meta-analysis suggested that an HP infection was associated with an increased risk of NAFLD for Asian and non-Asian populations. However, the association was not found for Asian males. Further studies are required to establish the causal association, especially for the non-Asian population.Systematic review registrationIdentifier: CRD42021266871.

Possible association between Helicobacter pylori infection (HPI) and nonalcoholic fatty liver disease (NAFLD) has been proposed by several studies with inconsistent conclusions. Here, we studied the association between HPI and NAFLD at 3 levels: (i) genetic level; (ii) small molecular level; and (iii) clinical level. Relation data between diseases, genes, and small molecules were acquired from Pathway Studio ResNet Mammalian database. Clinical data were acquired from 2263 elderly South Chinese subjects, including 603 NAFLD patients and 1660 subjects without NAFLD. Results showed that HPI and NAFLD present significantly shared genetic bases (95 genes, p value = 2.5E-72), demonstrating multiple common genetic pathways (enrichment p value ≤ 4.38E-20 for the top 10 pathways). Genetic network analysis suggested that mutual regulation may exist between HPI and NAFLD through 21 out of 95 genes. Furthermore, 85 out of the 95 genes manifested strong interaction with 12 small molecules/drugs that demonstrate effectiveness in treating both diseases. Clinical results showed that HPI rate in the NAFLD group was significantly higher than that in the group without NAFLD (51.9% vs. 43.6%; p value = 4.9E-4). Multivariate logistic regression results supported the observations and suggested that HPI served as a risk factor for NAFLD in the experiment data studied (odds ratio: 1.387, p value = 0.018). Results from this study support the hypothesis that complex biological association may exist between HPI and NAFLD, which partially explains the significant clinical co-incidence in the elderly population of south China.

Helicobacter pylori infection in patients with nonalcoholic fatty liver disease

These recommendations are based on the following: (1) a formal review and analysis of the recently published world literature on the topic [Medline search up to June 2011]; (2) the American College of Physicians’ Manual for Assessing Health Practices and Designing Practice Guidelines; (3) guideline policies of the three societies approving this document; and (4) the experience of the authors and independent reviewers with regards to NAFLD. Intended for use by physicians and allied health professionals, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible and adjustable for individual patients. Specific recommendations are evidence-based wherever possible, and when such evidence is not available or inconsistent, recommendations are made based on the consensus opinion of the authors. To best characterize the evidence cited in support of the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1). The strength of recommendations in the GRADE system is classified as strong (1) or weak (2). The quality of evidence supporting strong or weak recommendations is designated by one of three levels: high (A), moderate (B) or low-quality (C). This is a practice guideline for clinicians rather than a review article and interested readers can refer to several comprehensive reviews published recently.

NAFLD vs. MAFLD – It is not the name but the disease that decides the outcome in fatty liver