Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

Svegliati‐Baroni, Gianluca; Patrı́cio, Belmiro; Lioci, Gessica; Macedo, M. Paula; Gastaldelli, Amalia

doi:10.3390/ijms21165820

Cited by 51 publications

(43 citation statements)

References 314 publications

(300 reference statements)

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“…Although there were no statistically significant differences, which was partly due to the high variation in the expression from mouse-to-mouse, the observed trends suggest that synbiotic yogurt feeding reduced inflammation in the intestinal tissues. Intestinal leakiness and inflammatory signals can pass through the liver and migrate to the pancreas through portal circulation [ 23 ]. Interestingly, we observed increases in leaky gut markers, such as lipopolysaccharide binding protein (LBP) and cluster of differentiation 14 (CD14) antigen, as well as increases in pro-inflammatory markers, such as tumor necrosis factor-alpha (TNF-α), in the liver of control yogurt-fed mice compared to the milk- and synbiotic yogurt-fed groups ( Figure 4 h–j).…”

Section: Resultsmentioning

confidence: 99%

A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome–Intestine–Pancreas Axis

Miller

Mainali

Nagpal

et al. 2021

IJMS

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The prevalence of type 2 diabetes mellitus (T2D) is increasing worldwide, and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be administered daily are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially available yogurt (control yogurt). Interestingly, we found that the feeding of the synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the gut microbiota composition compared to milk, while the control yogurt negatively modulated it by significantly increasing the abundance of detrimental bacteria such as Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected pancreatic islet morphology compared to the milk control, while the control yogurt demonstrated worse effects on islets. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a therapeutic to prevent diabetes progression.

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Section: Resultsmentioning

confidence: 99%

A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome–Intestine–Pancreas Axis

Miller

Mainali

Nagpal

et al. 2021

IJMS

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“…As NAFLD and non-alcoholic stateohepatitis (NASH) are closely related to macro-cardiovascular events and are associated with reduced life expectancy, early and appropriate therapeutic intervention is essential [ 16 ]. However, despite the role of incretin hormones in NAFLD pathogenesis [ 17 ] and various interventions targeting the gut-pancreas-liver axis, in NASH treatment no approved treatment is currently available [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

et al. 2021

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Introduction To evaluate the efficacy of empagliflozin compared to pioglitazone in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM). Methods In this prospective randomized, double-blind, placebo-controlled trial, we assigned 106 patients with NAFLD and T2DM to receive empagliflozin 10 mg ( n = 35), pioglitazone 30 mg ( n = 34), or placebo ( n = 37) for 24 weeks. Liver fat content and liver stiffness were measured using fibroscans. Body composition assessment was performed by dual-energy x-ray absorptiometry (DEXA) scans. The primary end point was change from baseline in liver steatosis, using the controlled attenuation parameter (CAP) score. Results A borderline significant decrease in CAP score was observed with empagliflozin compared to placebo, mean difference: − 29.6 dB/m (− 39.5 to − 19.6) versus − 16.4 dB/m (− 25.0 to − 7.8), respectively; p = 0.05. Using multivariate analysis, we observed a significant reduction in the placebo-corrected change in liver stiffness measurement (LSM) with empagliflozin compared to pioglitazone: − 0.77 kPa (− 1.45, − 0.09), p = 0.02, versus 0.01 kPa (95% CI − 0.70, 0.71, p = 0.98), p for comparison = 0.03. Changes in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), HOMA2-IR, fibrosis-4 index (FIB4 index), NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index (APRI), android/gynecoid ratio (A/G ratio), and skeletal muscle index (SMI) were comparable between the two treatment groups, while significant reductions of the body weight and visceral fat area were observed only in the empagliflozin group ( p < 0.001 and p = 0.01, respectively) and both were increased in the placebo and pioglitazone groups. There were no serious adverse events in either group. Conclusion Treatment for 24 weeks with empagliflozin, in contrast to pioglitazone, was associated with improvement of liver steatosis and fibrosis in patients with NAFLD and T2DM. In addition, body weight and abdominal fat area were decreased in the empagliflozin group. Trial Registration Iranian Registry of Clinical Trials (IRCT), IRCT20190122042450N3. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01011-3.

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“…[9] Several studies have identified bacterial genera, families, and phyla that differ significantly in NAFLD and are implicated in the disease pathogenesis through increased intestinal permeability (i.e., Lachnospiraceae), decreased short chain fatty acids (SCFA) production (i.e., Faecalibacterium), and elevated serum endotoxin production (i.e., Bacteroides, Enterobacteriaceae). [10,11] While lifestyle modification remains the main mode of therapy, [1] still there is an unmet need for new treatments, with natural products being explored as candidates. [12] Mastiha is a natural nutritional supplement based on the dried resinous exudate from stems and branches of the tree Pistacia lentiscus.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Mastiha supplementation on NAFLD: The MAST4HEALTH Randomised, Controlled Trial

Amerikanou

Kanoni

Kaliora

et al. 2021

Molecular Nutrition Food Res

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and On behalf of MAST4HEALTH consortium Scope: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease with poor therapeutic strategies. Mastiha possesses antioxidant/anti-inflammatory and lipid-lowering properties. The authors investigate the effectiveness of Mastiha as a nonpharmacological intervention in NAFLD. Methods and Results: Ninety-eight patients with NAFLD in three countries (Greece, Italy, Serbia) are randomly allocated to either Mastiha or Placebo for 6 months, as part of a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The authors assess NAFLD severity via magnetic resonance imaging (MRI) scanning and LiverMultiScan technique and evaluate the effectiveness of Mastiha through medical, anthropometric, biochemical, metabolomic, and microbiota assessment. Mastiha is not superior to Placebo on changes in iron-corrected T1 (cT1) and Liver Inflammation Fibrosis score (LIF) in entire patient population; however, after BMI stratification (BMI ≤ 35 kg m -2 and BMI > 35 kg m -2 ), severely obese patients show an improvement in cT1 and LIF in Mastiha versus Placebo. Mastiha increases dissimilarity of gut microbiota, as shown by the Bray-Curtis index, downregulates Flavonifractor, a known inflammatory taxon and decreases Lysophosphatidylcholines-(LysoPC) 18:1, Lysophosphatidylethanolamines-(LysoPE) 18:1, and cholic acid compared to Placebo. Conclusion: Mastiha supplementation improves microbiota dysbiosis and lipid metabolite levels in patients with NAFLD, although it reduces parameters of liver inflammation/fibrosis only in severely obese patients.

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Gut-Pancreas-Liver Axis as a Target for Treatment of NAFLD/NASH

Cited by 51 publications

References 314 publications

A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome–Intestine–Pancreas Axis

A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome–Intestine–Pancreas Axis

Empagliflozin Improves Liver Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Effect of Mastiha supplementation on NAFLD: The MAST4HEALTH Randomised, Controlled Trial

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