Gut Microbiota as a Driver of Inflammation in Nonalcoholic Fatty Liver Disease

Bibbò, Stefano; Ianiro, Gianluca; Dore, Maria Pina; Simonelli, Claudia; Newton, Estelle E.; Cammarota, Giovanni

doi:10.1155/2018/9321643

Cited by 64 publications

(70 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Dysbiosis plays a main role in increasing intestinal permeability, which permits passage of bacteria‐derived products such as LPS into the portal circulation. In addition to IBD, dysbiosis, intestinal permeability and the ensuing inflammation, has been associated with numerous diseases including NEC, allergies, nonalcoholic fatty liver disease (NAFLD), cardiovascular disease, rheumatoid arthritis, and numerous neurological disorders such as bipolar, schizophrenia, autism, and Parkinson's . Systemic inflammation was assessed using an inflammatory cytokine protein array that detects 40 different inflammatory cytokines.…”

Section: Resultsmentioning

confidence: 99%

Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions

Podany

Rauchut

et al. 2018

Molecular Nutrition Food Res

View full text Add to dashboard Cite

Scope Greater than 68% of young infants are exposed to dietary zinc (Zn) levels that are higher than the Tolerable Upper Intake Limit. However, the consequences of excess dietary Zn during early life on intestinal function and host–microbe interactions are unknown. Methods and Results Neonatal mice are gavaged with 100 Zn µg d–1 from postnatal day (PN) 2 through PN10 and indices of intestinal function and host–microbe interactions are compared to unsupplemented mice. Excess dietary Zn causes oxidative stress, increases goblet cell number and mucus production, and are associated with increased intestinal permeability and systemic inflammation. Over 900 genes are differentially expressed; 413 genes display a fold‐change >1.60. The Gene Ontology Biological processes most significantly affected include biological adhesion, the immune system, metabolic processes, and response to stimulus. Key genes most highly and significantly upregulated include ALDH2, MT1, TMEM6, CDK20, and COX62b, while CALU, ST3GAL4, CRTC2, SLC28A2, and COMMA1 are downregulated. These changes are associated with a microbiome enriched in pathogenic taxa including Pseudomonadales and Campylobacter, and greater expression of bacterial stress response genes. Conclusion Excess dietary Zn may have unforeseen influences on epithelial signaling pathways, barrier function, and luminal ecology in the intestine that may have long‐term consequences on intestinal health.

show abstract

Section: Resultsmentioning

confidence: 99%

Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions

Podany

Rauchut

et al. 2018

Molecular Nutrition Food Res

View full text Add to dashboard Cite

show abstract

“…IRFs are recognized to work in the progression of NAFLD in addition to their original functions which are the regulation of the expression of type I IFN and IFN-induced genes. [145][146][147][148][149] In addition, short-chain fatty acids (SCFAs), including propionic, butyric and acetic acids, are the main products of carbohydrates digested by gut bacteria. IRF3 is proved to alleviate the lipid accumulation and to improve IR in the liver, and IRF9 can be used to ameliorate steatosis and inflammation.…”

Section: Inflammation and Innate Immunitymentioning

confidence: 99%

Insights into the Epidemiology, Pathogenesis, and Therapeutics of Nonalcoholic Fatty Liver Diseases

et al. 2018

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease which affects ≈25% of the adult population worldwide, placing a tremendous burden on human health. The disease spectrum ranges from simple steatosis to steatohepatitis, fibrosis, and ultimately, cirrhosis and carcinoma, which are becoming leading reasons for liver transplantation. NAFLD is a complex multifactorial disease involving myriad genetic, metabolic, and environmental factors; it is closely associated with insulin resistance, metabolic syndrome, obesity, diabetes, and many other diseases. Over the past few decades, countless studies focusing on the investigation of noninvasive diagnosis, pathogenesis, and therapeutics have revealed different aspects of the mechanism and progression of NAFLD. However, effective pharmaceuticals are still in development. Here, the current epidemiology, diagnosis, animal models, pathogenesis, and treatment strategies for NAFLD are comprehensively reviewed, emphasizing the outstanding breakthroughs in the above fields and promising medications in and beyond phase II.

show abstract

“…Gut dysbiosis exposes the liver to a large amount of pathogen‐associated molecular patterns (PAMPs): lipopolysaccharide, DNA, RNA and endotoxins. All of these activate TLRs on Kupffer cell surface and then the downstream myeloid differentiation primary response 88 (MyD88) signal, which ultimately lead to nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) transcription and expression of pro‐inflammatory cytokines and chemokines 57 . Alongside pro‐inflammatory response, TLR activation triggers a wide range of pathological processes ranging from inflammasome activation to apoptosis.…”

Section: Fatty Liver Disease: Crosstalk With Surrounding Tissuesmentioning

confidence: 99%

Macrophages in the pathophysiology of NAFLD: The role of sex differences

Ministrini

Montecucco

Sahebkar

et al. 2020

Eur J Clin Investigation

View full text Add to dashboard Cite

Nonalcoholic fatty liver disease (NAFLD) is a multifactorial pathological condition, which recognizes a certain sexual dimorphism. Experimental and clinical studies provided evidence for a critical role of macrophages in NAFLD development and progression. Especially, liver-resident macrophages (also known as Kupffer cells) are likely the common final pathway of several pro-steatosic signals. A huge amount of danger-associated molecular patterns recognized by Kupffer cells is provided within the liver by lipid and glucose toxicity. Other pro-inflammatory signals come from surrounding tissues into the portal vein, directly to the liver: they come from dysfunctional adipocytes, adipose tissue macrophages and gut dysbiosis. These complex crosstalks are differently represented across sexes, as sexual hormones control many of these processes. Sexual dimorphism then modulates metabolic and inflammatory cascades driving the liver from a simple steatosis to NAFLD and beyond.Here, metabolic and inflammatory mechanisms underlying NALFD pathophysiology will be updated. A special attention will be paid to describe sex-related differences that could provide insights for patient stratification and more tailored therapeutic approaches. K E Y W O R D Sinflammation, Kupffer cells, macrophages, microbiome, nonalcoholic fatty live disease 2 of 9 | MINISTRINI eT al.

show abstract

Gut Microbiota as a Driver of Inflammation in Nonalcoholic Fatty Liver Disease

Cited by 64 publications

References 69 publications

Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions

Excess Dietary Zinc Intake in Neonatal Mice Causes Oxidative Stress and Alters Intestinal Host–Microbe Interactions

Insights into the Epidemiology, Pathogenesis, and Therapeutics of Nonalcoholic Fatty Liver Diseases

Macrophages in the pathophysiology of NAFLD: The role of sex differences

Contact Info

Product

Resources

About