Contribution of gut microbiota to nonalcoholic fatty liver disease: Pathways of mechanisms

Bakhshimoghaddam, Farnush; Alizadeh, Mohammad

doi:10.1016/j.clnesp.2021.05.012

Cited by 21 publications

(16 citation statements)

References 61 publications

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“…Moreover, donor fecal microbiota transplantation studies performed in human subjects confirmed that the gut dysbiosis can per se cause hepatic steatosis mainly by means of weight gain, insulin resistance, and increased OS [67,181,182]. The hypothesized mechanisms are greater efficiency in energy absorption from food, modification of the intestinal permeability, release of intestinal hormones, and inflammation, with a relevant role for OS induction [183][184][185][186][187][188][189].…”

Section: Role Of Microbiota In Hepatic Steatosis and Oxidative Stressmentioning

confidence: 95%

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Smirne

Croce

Benedetto

et al. 2022

Livers

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Non-alcoholic fatty liver disease (NAFLD) is a challenging disease caused by multiple factors, which may partly explain why it still remains an orphan of adequate therapies. This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism. Several reactive oxygen species generators, including those produced in the gastrointestinal tract, contribute to the lipotoxic hepatic (and extrahepatic) damage by fatty acids and a great variety of their biologically active metabolites in a “multiple parallel-hit model”. This leads to inflammation and fibrogenesis and contributes to NAFLD progression. The alterations of the oxidant/antioxidant balance affect also metabolism-related organelles, leading to lipid peroxidation, mitochondrial dysfunction, and endoplasmic reticulum stress. This OS-induced damage is at least partially counteracted by the physiological antioxidant response. Therefore, modulation of this defense system emerges as an interesting target to prevent NAFLD development and progression. For instance, probiotics, prebiotics, diet, and fecal microbiota transplantation represent new therapeutic approaches targeting the gut microbiota dysbiosis. The OS and its counter-regulation are under the influence of individual genetic and epigenetic factors as well. In the near future, precision medicine taking into consideration genetic or environmental epigenetic risk factors, coupled with new OS biomarkers, will likely assist in noninvasive diagnosis and monitoring of NAFLD progression and in further personalizing treatments.

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Section: Role Of Microbiota In Hepatic Steatosis and Oxidative Stressmentioning

confidence: 95%

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Smirne

Croce

Benedetto

et al. 2022

Livers

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“…Accumulating evidence from published studies suggests a multifactorial contribution of SIBO in the development and progression of NAFLD [ 17 , 18 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. The main proposed mechanisms include a disturbance of energy homeostasis leading to energy salvage, increased oxidative stress, enhancement of insulin resistance, increased ethanol production, and alterations in the metabolism of choline and bile acids [ 18 , 31 , 46 ]. Nucleotide-binding oligomerisation domain-like receptor protein NLRP3 and NLRP6, which belong to the family of inflammasomes, balance the immune response with the expression of interleukin IL-1b and IL-18, serving as regulators of normal microbiota and ameliorating NAFLD, whereas dysbiosis has been associated with a decrease in those inflammasomes and NAFLD occurrence in animal models [ 47 , 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…Portal circulation and the liver–gut axis can also comprise the pathways of bacterial translocation to the liver, accompanied by pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), which are recognized triggering factors of chronic inflammatory responses [ 50 ]. Moreover, increased permeability due to tight cell junctions disruption found in SIBO patients can lead to the translocation of bacteria and their products, such as endotoxins, while endotoxemia further induces CD14 mRNA and nuclear factor kappa B (NF-kB) expression that consequently activates Toll-like receptor 4 (TLR-4) and stimulates the production of proinflammatory cytokines such as tumor necrosis factor α (TNF-α), IL-1β, IL-6, and IL-8 [ 31 , 34 , 35 , 46 ]. Overproduction of these cytokines, but also the direct effect of bacterial products, such as lipopolysaccharides, contribute to the development of inflammation and insulin resistance and may be essential in the pathogenesis of NASH, liver fibrosis, and hepatocellular carcinoma [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Small Intestinal Bacterial Overgrowth Syndrome in Patients with Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis: A Cross-Sectional Study

Gkolfakis

Tziatzios

Leite³

et al. 2023

Microorganisms

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Introduction: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial, wide-spectrum liver disorder. Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the number and/or type of colonic bacteria in the upper gastrointestinal tract. SIBO, through energy salvage and induction of inflammation, may be a pathophysiological factor for NAFLD development and progression. Aim/Methods: Consecutive patients with histological, biochemical, or radiological diagnosis of any stage of NAFLD (non-alcoholic fatty liver [NAFL], non-alcoholic steatohepatitis [NASH], cirrhosis) underwent upper gastrointestinal endoscopy. Duodenal fluid (2cc) was aspirated from the 3rd–4th part of duodenum into sterile containers. SIBO was defined as ≥103 aerobic colony-forming units (CFU)/mL of duodenal aspirate and/or the presence of colonic-type bacteria. Patients without any liver disease undergoing gastroscopy due to gastroesophageal reflux disease (GERD) comprised the healthy control (HC) group. Concentrations (pg/mL) of tumor necrosis factor alpha (TNFα), interleukin (IL)-1β, and IL-6 were also measured in the duodenal fluid. The primary endpoint was to evaluate the prevalence of SIBO in NAFLD patients, while the comparison of SIBO prevalence among NAFLD patients and healthy controls was a secondary endpoint. Results: We enrolled 125 patients (51 NAFL, 27 NASH, 17 cirrhosis, and 30 HC) aged 54 ± 11.9 years and with a weight of 88.3 ± 19.6 kg (NAFLD vs. HC 90.7 ± 19.1 vs. 80.8 ± 19.6 kg, p = 0.02). Overall, SIBO was diagnosed in 23/125 (18.4%) patients, with Gram-negative bacteria being the predominant species (19/23; 82.6%). SIBO prevalence was higher in the NAFLD cohort compared to HC (22/95; 23.2% vs. 1/30; 3.3%, p = 0.014). Patients with NASH had higher SIBO prevalence (6/27; 22.2%) compared to NAFL individuals (8/51; 15.7%), but this difference did not reach statistical significance (p = 0.11). Patients with NASH-associated cirrhosis had a higher SIBO prevalence compared to patients with NAFL (8/17; 47.1% vs. 8/51; 15.7%, p = 0.02), while SIBO prevalence between patients with NASH-associated cirrhosis and NASH was not statistically different (8/17; 47.1% vs. 6/27; 22.2%, p = 0.11). Mean concentration of TNF-α, IL-1β, and IL-6 did not differ among the different groups. Conclusion: The prevalence of SIBO is significantly higher in a cohort of patients with NAFLD compared to healthy controls. Moreover, SIBO is more prevalent in patients with NASH-associated cirrhosis compared to patients with NAFL.

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“…Human gut microbiota is composed of a mosaic of microorganisms that vary between individuals, which represents personalized microbiological identity [6]. More than 90% of the total microbial population in humans are dominated by four bacterial phyla: Firmicutes (40%), Bacteroidetes (19.7%), Actinobacteria (2.15%), and Proteobacteria (2.15%) [3,[14][15][16]. The quantitative and qualitative imbalance between these phyla, which occurs in SIBO, seems to be the key to the origin of various pathologies [6,10,[17][18][19][20][21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Small Intestinal Bacterial Overgrowth in Patients with Roux-en-Y Gastric Bypass and One-Anastomosis Gastric Bypass

Novljan

Pintar

2022

OBES SURG

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Background Small intestinal bacterial overgrowth (SIBO) is defined as an excessive growth and/or changed composition of bacteria in the small bowel. Obese patients are at increased risk of SIBO and related complications. The purpose of this study is to evaluate the incidence of SIBO after bariatric bypass procedures, connection between SIBO, symptoms, comorbidities, and liver pathology. Methods Patients underwent a hydrogen breath test with glucose substrate (25 g/200 ml of water). The demographic, anthropometric data, comorbidities, and symptoms were analysed with a questionnaire. In 45 patients, the NAFLD Activity Score was evaluated in liver biopsies. Results Glucose breath test was positive in 24/56 (43%) of patients and was associated with higher frequency of defecation (p = 0.022), lactose intolerance (p = 0.047), scleroderma (p = 0.042), irritable bowel syndrome (p = 0.018), and diabetes (p = 0.002). Mean NAFLD Activity Score in SIBO patients (n = 18) was 3.33 and 3.00 in non-SIBO patients (n = 27). In SIBO-positive cohort of patients, a statistically important trend in difference between NAS and difference to range value anti-Xa 4 h after subtherapeutic dose application was calculated. Conclusions The incidence of SIBO after bariatric surgery bypass procedures is alarmingly high (43%). The results of our study conclude that diagnosis cannot be set based on specific symptom and SIBO is related to reduced response to the application of LMWH. Mandatory SIBO screening and appropriate treatment would affect the clinical outcome of the underlying disease, improve it significantly, and prevent the development of its complications. Graphical abstract

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Contribution of gut microbiota to nonalcoholic fatty liver disease: Pathways of mechanisms

Cited by 21 publications

References 61 publications

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

Prevalence of Small Intestinal Bacterial Overgrowth Syndrome in Patients with Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis: A Cross-Sectional Study

Small Intestinal Bacterial Overgrowth in Patients with Roux-en-Y Gastric Bypass and One-Anastomosis Gastric Bypass

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