Bifidobacteria and lactobacilli in the gut microbiome of children with non-alcoholic fatty liver disease: which strains act as health players?

Abstract

IntroductionNon-alcoholic fatty liver disease (NAFLD), considered the leading cause of chronic liver disease in children, can often progress from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). It is clear that obesity is one of the main risk factors involved in NAFLD pathogenesis, even if specific mechanisms have yet to be elucidated. We investigated the distribution of intestinal bifidobacteria and lactobacilli in the stools of four groups of children: obese, obese with NAFL, obese with NASH, and healthy, age-matched controls (CTRLs).Material and methodsSixty-one obese, NAFL and NASH children and 54 CTRLs were enrolled in the study. Anthropometric and metabolic parameters were measured for all subjects. All children with suspected NASH underwent liver biopsy. Bifidobacteria and lactobacilli were analysed in children’s faecal samples, during a broader, 16S rRNA-based pyrosequencing analysis of the gut microbiome.ResultsThree Bifidobacterium spp. (Bifidobacterium longum, Bifidobacterium bifidum, and Bifidobacterium adolescentis) and five Lactobacillus spp. (L. zeae, L. vaginalis, L. brevis, L. ruminis, and L. mucosae) frequently recurred in metagenomic analyses. Lactobacillus spp. increased in NAFL, NASH, or obese children compared to CTRLs. Particularly, L. mucosae was significantly higher in obese (p = 0.02426), NAFLD (p = 0.01313) and NASH (p = 0.01079) than in CTRLs. In contrast, Bifidobacterium spp. were more abundant in CTRLs, suggesting a protective and beneficial role of these microorganisms against the aforementioned diseases.ConclusionsBifidobacteria seem to have a protective role against the development of NAFLD and obesity, highlighting their possible use in developing novel, targeted and effective probiotics.

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

“…Numerous human studies have demonstrated an association between gut dysbiosis and the spectrum of NAFLD in children 7–10 and adults 11–23 . All except one of these studies were cross-sectional 12 , and the majority utilized biomarker-based sequencing to profile the gut microbiome.…”

“…In NAFL, comparison groups included healthy controls 9,8,10,11,15,16,18,23 and obese controls 21 . In NASH, comparison groups included healthy controls 9,10,12,13,18,19 , obese controls 7 , and NAFL 24,16 . In NAFLD-associated advanced fibrosis, comparison groups included healthy controls 20 and NAFLD without advanced fibrosis (stage<2) 17,24,22,16 .…”

Microbiome diurnal rhythmicity and its impact on host physiology and disease risk

“…Through the portal vein that connects the liver to the gastrointestinal tract, the liver is exposed to the influence of the gut microbiome. Perturbations of the gut microbiome, coupled with disturbances in gut barrier function, have been associated with common liver disorders, such as non-alcoholic fatty liver disease [138][139][140], non-alcoholic steatohepatitis [139,[141][142][143][144][145][146][147][148][149][150][151][152], alcoholic liver disease [139,140,142,145,147,148,150,151,[153][154][155][156][157][158][159][160][161][162][163][164], and liver cirrhosis [165][166][167][168][169][170]. Thus, the microbiome serves as a modulator of liver rhythmic functions.…”

Gut Microbial Metabolism and Nonalcoholic Fatty Liver Disease

“…A number of cross‐sectional human studies have demonstrated an association between gut microbiota perturbation and the full clinical spectrum of NAFLD, including nonalcoholic fatty liver without steatohepatitis (NAFL), NASH, NAFLD‐related advanced fibrosis (fibrosis stage >2), and NAFLD‐related cirrhosis and hepatocellular carcinoma . Several of these studies were performed in pediatric cohorts, and an overwhelming majority of these studies used biomarker‐based sequencing to profile the gut microbiota.…”