Antibiotic use and development of nonalcoholic fatty liver disease: A population‐based case–control study

Abstract

Background and AimsAntibiotics affect the gut microbiome. Preclinical studies suggest a role of gut dysbiosis in the development of nonalcoholic fatty liver disease (NAFLD), but data from large cohorts with liver histology are lacking.MethodsIn this nationwide case–control study, Swedish adults with histologically confirmed early‐stage NAFLD (total n = 2584; simple steatosis n = 1435; steatohepatitis (NASH) n = 383; non‐cirrhotic fibrosis n = 766) diagnosed January 2007–April 2017 were included and matched to ≤5 population controls (n = 12 646) for age, sex, calendar year and county of residence. Data for cumulative antibiotic dispensations and defined daily doses were accrued until 1 year before the matching date. Using conditional logistic regression, multivariable‐adjusted odds ratios (aORs) were calculated. In a secondary analysis, NAFLD patients were compared with their full siblings (n = 2837).ResultsPrevious antibiotic use was seen in 1748 (68%) NAFLD patients versus 7001 (55%) controls, corresponding to 1.35‐fold increased odds of NAFLD (95% CI = 1.21–1.51) in a dose‐dependent manner (pfor trend < .001). Estimates were comparable for all histologic stages (p > .05). The highest risk of NAFLD was observed after treatment with fluoroquinolones (aOR 1.38; 95% CI = 1.17–1.59). Associations remained robust when patients were compared with their full siblings (aOR 1.29; 95% CI = 1.08–1.55). Antibiotic treatment was only linked to NAFLD in patients without metabolic syndrome (aOR 1.63; 95% CI = 1.35–1.91) but not in those with metabolic syndrome (aOR 1.09; 95% CI = 0.88–1.30).ConclusionsAntibiotic use may be a risk factor for incident NAFLD, especially in individuals without the metabolic syndrome. The risk was highest for fluoroquinolones and remained robust in sibling comparisons with whom individuals share genetic and early environmental susceptibilities.

Could Adverse Effects of Antibiotics Due to Their Use/Misuse Be Linked to Some Mechanisms Related to Nonalcoholic Fatty Liver Disease?

“…An-tibiotic use was found to be a risk factor for incident NAFLD, especially in individuals without metabolic syndrome. The risk was very significant for fluoroquinolones and remained robust in sibling comparisons with whom individuals shared genetic and early environmental susceptibilities [60].…”

Subtherapeutic Kitasamycin Promoted Fat Accumulation in the Longissimus Dorsi Muscle in Growing–Finishing Pigs

“…Consequently, many countries have restricted or prohibited the use of antibiotics as growth promoters in livestock [4,5]. Furthermore, recent Animals 2024, 14, 1057. https://doi.org/10.3390/ani14071057 https://www.mdpi.com/journal/animals clinical and rodent research has suggested a potential link between antibiotics and obesityrelated metabolic disorders, with specific antibiotics implicated in gut microbiota changes and lipid ectopic deposition [6][7][8][9][10]. The altered gut microbiota has been reported to play a key role in host metabolism, as indicated by the ability to replicate metabolic disorders in germ-free recipients inoculated with penicillin-altered bacteria [11].…”