Periodontal pathogenic bacteria, Aggregatibacter actinomycetemcomitans affect non-alcoholic fatty liver disease by altering gut microbiota and glucose metabolism

by | Oct 24, 2017 | Gastrointestinal | 0 comments

Increasing evidence indicates that periodontitis affects non-alcoholic fatty liver disease (NAFLD). We examined the relationship between periodontal bacterial infection and clinical/biochemical parameters in 52 NAFLD patients. Anti-Aggregatibacter actinomycetemcomitans (Aa) antibody titers correlated positively with visceral fat, fasting plasma insulin, and HOMA-IR; and negatively with the liver/spleen ratio. C57BL/6J mice (8-weeks-old) were given Aa or saline (control) for 6 weeks, and were fed either normal chow (NCAa, NCco) or high-fat diet (HFAa and HFco). NCAa and HFAa mice presented impaired glucose tolerance and insulin resistance compared to control mice. HFAa mice showed higher hepatic steatosis than HFco animals. Liver microarray analysis revealed that 266 genes were differentially expressed between NCAa and NCco mice. Upregulated genes in Aa-administrated mice were enriched for glucagon signaling pathway, adipocytokine signaling pathway and insulin resistance. Consistently, plasma glucagon concentration was higher in NCAa mice. In addition, Akt phosphorylation was lower in the liver of NCAa/HFAa than in NCco/HFco mice. Based on 16S rRNA sequencing, Aa administration changed composition of the gut microbiota. Metagenome prediction in gut microbiota showed upregulation of fatty acid biosynthesis and downregulation of fatty acid degradation in Aa-administered mice. Thus, infection with Aa affects NAFLD by altering the gut microbiota and glucose metabolism.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. NAFLD includes a wide spectrum of conditions ranging from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). Generally, NAFL shows a non-progressive clinical course, whereas NASH is a more serious form of NAFLD and can progress to cirrhosis or hepatocellular carcinoma1,2. Many risk factors related to the development of NAFLD have been proposed, such as obesity, diabetes, and insulin resistance3,4.

Periodontal disease is an inflammatory disorder caused by pathogenic oral microorganisms that can lead to the destruction of alveolar bone and connective tissues around the teeth5,6. Periodontal bacteria present in dental plaque possess various virulence factors, such as lipopolysaccharide (LPS), fimbriae, and enzymes, which can trigger inflammation in periodontal tissues7. Considering that the bacterial flora of the oral cavity differs from that of the gut8, there is a possibility that swallowed bacteria could affect the composition of gut microbiome.

Given the infectious nature of periodontal disease, patients with the disease show elevated IgG antibody titers against periodontopathic bacteria. These antibody titers correlate with severity of periodontal disease9. Periodontal infection has long been associated with an increased risk of various diseases, such as atherosclerotic vascular disease10 or type 2 diabetes11. Recently, several studies have indicated that periodontitis might influence NAFLD12,13. In addition, gut microbiota appear to mediate development and progression of NAFLD14,15,

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