Development of hepatocellular carcinoma in patients with cirrhosis is associated with alterations in intestinal microbiota, including an escalation of dysbiosis and reduced bacterial richness. This study demonstrates that reduced bacterial richness and dysbiosis escalate with the progression of cirrhosis from compensated to decompensated cirrhosis and to HCC-associated cirrhosis (HCC-cirrhosis). Moreover, we report for the first time the effect of environmental factors on HCC-cirrhosis. Excess weight was associated with increased dysbiosis in patients with HCC compared to their normal-weight counterparts. Moreover, fatty liver, consumption of artificial sweeteners, and high-sugar foods were associated with altered microbial composition, including altered levels of Akkermansia muciniphila in HCC-cirrhosis. We have successfully determined that levels of Alphaproteobacteria and the two genera CF231 and Clostridium are significantly altered in cirrhotic patients who develop hepatocellular carcinoma, independently of cirrhosis severity and dietary habits.

The intestinal microbiome continues to shift and develop throughout youth and could play a pivotal role in health and wellbeing throughout adulthood. Environmental and interpersonal determinants are strong mediators of the intestinal microbiome during the rapid growth period of preadolescence. We aim to delineate associations between the gut microbiome composition, body mass index (BMI), dietary intake and socioeconomic status (SES) in a cohort of ethnically homogenous preadolescents. This cohort included 139 Arab children aged 10–12 years, from varying socioeconomic strata. Dietary intake was assessed using the 24-h recall method. The intestinal microbiome was analyzed using 16S rRNA gene amplicon sequencing. Microbial composition was associated with SES, showing an overrepresentation of Prevotella and Eubacterium in children with lower SES. Higher BMI was associated with lower microbial diversity and altered taxonomic composition, including higher levels of Collinsella, especially among participants from lower SES. Intake of polyunsaturated fatty acids was the strongest predictor of bacterial alterations, including an independent association with Lachnobacterium and Lactobacillus. This study demonstrates that the intestinal microbiome in preadolescents is associated with socioeconomic determinants, BMI and dietary intake, specifically with higher consumption of polyunsaturated fatty acids. Thus, tailored interventions during these crucial years have the potential to improve health disparities throughout the lifespan.

The development of the gut microbiome occurs mainly during the first years of life; however, little is known on the role of environmental and socioeconomic exposures, particularly within the household, in shaping the microbial ecology through childhood. We characterized differences in the gut microbiome of school-age healthy children, in association with socioeconomic disparities and household crowding. Stool samples were analyzed from 176 Israeli Arab children aged six to nine years from three villages of different socioeconomic status (SES). Sociodemographic data were collected through interviews with the mothers. We used 16 S rRNA gene sequencing to characterize the gut microbiome, including an inferred analysis of metabolic pathways. Differential analysis was performed using the analysis of the composition of microbiomes (ANCOM), with adjustment for covariates. An analysis of inferred metagenome functions was performed implementing PICRUSt2. Gut microbiome composition differed across the villages, with the largest difference attributed to socioeconomic disparities, with household crowding index being a significant explanatory variable. Living in a low SES village and high household crowding were associated with increased bacterial richness and compositional differences, including an over-representation of Prevotella copri and depleted Bifidobacterium. Secondary bile acid synthesis, d-glutamine and d-glutamate metabolism and Biotin metabolism were decreased in the lower SES village. In summary, residential SES is a strong determinant of the gut microbiome in healthy school-age children, mediated by household crowding and characterized by increased bacterial richness and substantial taxonomic and metabolic differences. Further research is necessary to explore possible implications of SES-related microbiome differences on children’s health and development.