Multiple gut–liver axis abnormalities in children with obesity with and without hepatic involvement

Nuzio, Salvatore Guercio; Stasi, Martina Di; Pierri, Luca; Troisi, Jacopo; Poeta, Marco; Bisogno, A.; Belmonte, F.; Tripodi, Marie Françoise; Salvio, D. Di; Massa, G; Savastano, Riccardo; Cavallo, Pierpaolo; Boffardi, Massimo; Ziegenhardt, Doreen; Bergheim, Ina; Mandato, Claudia; Vajro, Pietro

doi:10.1111/ijpo.12164

Cited by 41 publications

(31 citation statements)

References 28 publications

(32 reference statements)

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“…Increased IP, gut microbiota dysbiosis, and SIBO have been associated with the severity of obesity-related liver damage [3,5,43,44]. Therefore, it is not surprising that a large percentage of our obese children with NAFLD showed signals of metabolome signature associated with gut-liver axis malfunctioning.…”

Section: Discussionmentioning

confidence: 99%

“…Several lines of evidence indicate that specific gut microbiota may play a role in obesity, metabolic syndrome, and fatty liver by increasing energy harvesting in conditions of intestinal dysbiosis or small intestinal bacterial overgrowth (SIBO) [3,4]. In the presence of a damaged intestinal barrier (“leaky gut”), the gut-liver axis (GLA) may amplify he normal interactions between intestinal bacteria/bacterial products and hepatic receptors [5], thereby promoting a cascade of events, namely, oxidative stress, insulin-resistance (IR), hepatic inflammation and fibrosis, via a large number of metabolites [6].…”

Section: Introductionmentioning

confidence: 99%

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Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

et al. 2017

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To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass index <85th or >95th percentile, respectively) ± ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was increased in all obese children (p = 0.0022), IP preferentially in those with NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary metabolome correctly allocated children based on their obesity, NAFLD, visceral fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients; and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter especially in children without NAFLD. The metabolic pathways of BCAA and/or their metabolites correlated with excess of visceral fat centimeters (leucine/oxo-valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome analysis contributes to define a metabolic fingerprint of pediatric obesity and related NAFLD, by identifying metabolic pathways/metabolites reflecting typical obesity dietary habits and GLA perturbations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

et al. 2017

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“…In support of this, Wong et al conducted a prospective cohort study in 920 adults and found that endotoxin markers were associated with the development of NAFLD . Furthermore, 2 recent studies showed that in obese children with and without NAFLD, intestinal permeability correlated with degree of hepatic involvement as well as blood ethanol and endotoxin levels, and urinary metabolome analyses identified metabolite changes associated with dietary habits, intestinal permeability, and SIBO . Additional microbial metabolites that may be important in NAFLD/NASH include short chain fatty acids (SCFAs) and bile acids.…”

Section: Gut Microbiota and Liver Diseasementioning

confidence: 96%

Microbiota and the liver

2018

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The gut microbiome outnumbers the human genome by 150-fold and plays important roles in metabolism, immune system education, tolerance development, and prevention of pathogen colonization. Dysbiosis has been associated with nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and alcoholic liver disease (ALD) as well as cirrhosis and complications. This article provides an overview of this relationship. Liver Transplantation 24 539-550 2018 AASLD.

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“…It is widely accepted that alterations in the gut-liver and gut-brain axes are important to paediatric and adult obesity, with decreased butyrate an important aspect of this [103]. The above would suggest that alterations in butyrate availability prenatally may also be relevant to the early developmental etiology of obesity and its associated complications in children and adults.…”

Section: Maternal Gut Microbiome and Pregnancymentioning

confidence: 99%

The Role of Prenatal Melatonin in the Regulation of Childhood Obesity

Ivanov

Evsyukova

Mazzoccoli

et al. 2020

Biology

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There is a growing awareness that pregnancy can set the foundations for an array of diverse medical conditions in the offspring, including obesity. A wide assortment of factors, including genetic, epigenetic, lifestyle, and diet can influence foetal outcomes. This article reviews the role of melatonin in the prenatal modulation of offspring obesity. A growing number of studies show that many prenatal risk factors for poor foetal metabolic outcomes, including gestational diabetes and night-shift work, are associated with a decrease in pineal gland-derived melatonin and associated alterations in the circadian rhythm. An important aspect of circadian melatonin’s effects is mediated via the circadian gene, BMAL1, including in the regulation of mitochondrial metabolism and the mitochondrial melatoninergic pathway. Alterations in the regulation of mitochondrial metabolic shifts between glycolysis and oxidative phosphorylation in immune and glia cells seem crucial to a host of human medical conditions, including in the development of obesity and the association of obesity with the risk of other medical conditions. The gut microbiome is another important hub in the pathoetiology and pathophysiology of many medical conditions, with negative consequences mediated by a decrease in the short-chain fatty acid, butyrate. The effects of butyrate are partly mediated via an increase in the melatoninergic pathway, indicating interactions of the gut microbiome with melatonin. Some of the effects of melatonin seem mediated via the alpha 7 nicotinic receptor, whilst both melatonin and butyrate may regulate obesity through the opioidergic system. Oxytocin, a recently recognized inhibitor of obesity, may also be acting via the opioidergic system. The early developmental regulation of these processes and factors by melatonin are crucial to the development of obesity and many diverse comorbidities.

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Multiple gut–liver axis abnormalities in children with obesity with and without hepatic involvement

Cited by 41 publications

References 28 publications

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations

Microbiota and the liver

The Role of Prenatal Melatonin in the Regulation of Childhood Obesity

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