Microbiota May Help Single Out ‘Lean’ NAFLD

Both fecal and blood microbiota profiles showed different patterns between participants with obese-type versus lean-type nonalcoholic fatty liver disease (NAFLD), and these may serve as diagnostic biomarkers to differentiate diverse phenotypes of this rapidly growing health problem, according to South Korean researchers.

In the gut microbiota, for example, a decrease in bacteria of the family Desulfovibrionaceae was associated with NAFLD in the lean NAFLD group (log2 coefficient -2.107), but not in the obese NAFLD group (1.440). Succinivibrionaceae showed opposite correlations in the lean NAFLD group, in which it was lower (log2 coeff. –1.349), and the obese group (log2 coeff. 2.215), in which it was not, reported Hwi Young Kim, MD, PhD, of Ewha Women’s University College of Medicine in Seoul, and colleagues.

In the blood microbiota, populations of Leucine Vibrionaceae showed opposite correlations in both the lean (log2 coeff. –1.349) and obese (log2 coeff. 2.215) NAFLD groups. Notably, the Leuconostocaceae family decreased in the obese NAFLD group in both the gut (log2 coeff. –1.168) and blood (log2 coeff. –2.250), they wrote in PLoS One.

NAFLD in both BMI groups was associated with reduced bacterial biodiversity compared with non-NAFLD controls, the authors added.

The findings “might serve as a microbiota signature to predict NAFLD particularly in lean subjects, before progression of NAFLD to significant fibrosis or cirrhosis,” they wrote. “In addition, a point-of-care test based on our blood microbiota characteristics might be anticipated if these results are properly validated in the near future.”

They pointed out that nonobese NAFLD patients tend to have less-severe disease, and may have a better prognosis than obese patients, according to a recent Asian study. The lean type is more prevalent in Asians but occurs in approximately 10% of Westerners.

The investigators reviewed demographic and clinical data in 268 health-checkup examinees seen from June to September 2014 at Kangbuk Samsung Hospital Total Healthcare Screening Centers in Seoul. NAFLD was diagnosed by ultrasound, and patients with NAFLD were further categorized as obese (BMI >25) or lean (BMI <25).

Because all participants had no evidence of liver diseases of other etiologies, all incident cases with fatty liver were regarded as NAFLD. Patients were compared with 192 controls with no evidence of NAFLD or other liver diseases. NAFLD patients were slightly older (45.3 vs 42.9 years) and more frequently male (72.4% vs 43.2%). They had higher average BMIs (25.7 vs 22.2), as well as higher blood pressure and metabolic and liver-related laboratory values than those without NAFLD (P≤0.05).

Among 195 lean study participants, the 27 (13.8%) found to have NAFLD also demonstrated significantly higher biometric and laboratory values, except for hemoglobin A1c and aspartate aminotransferase, than their lean control counterparts.

Although there was a distinct microbial community in the fecal microbiota of participants with lean NAFLD, this was not true for blood. “This discrepancy in ecological diversity between blood and fecal microbiota might have resulted from their genuine compositional difference due to the presence of intestinal barrier, filtering function of the liver, and the role of immune cells,” the authors wrote.

Additionally, microbiota in blood may derive from the mouth as well. The authors said their results need validation in other populations with different characteristics, such as body metrics and dietary habits.

A 2016 European pilot study demonstrated that changes in blood microbiota were associated with liver fibrosis in obese patients. A related study suggested that imbalances of certain gut bacteria could be used as a biomarker to identify patients at risk for pancreatic cancer and help target treatments.

Amon Asgharpour, MD, of the Icahn School of Medicine at Mount Sinai in New York City, commented that the study was “very intriguing … It was really interesting to see a difference in the microbiota of lean NAFLD patients and the more traditional obese patients.”

Asgharpour, who was not involved in the study, added that data have shown a microbial shift to gram-negative bacteria in NAFLD, and especially in its more aggressive counterpart, nonalcoholic hepatosteatitis. A greater abundance of gram-negative strains leads to more endotoxin in the gut, which leads to activation of inflammatory pathways, a pattern that may some day be leveraged therapeutically with appropriate blocking, he noted.

“But clinically, the findings are not yet ready, since our understanding of the microbiome is still in its infancy,” Asgharpour added. “The problem is that the microbiome can shift very rapidly, say, if someone switches from a vegan to a meat-eating diet, so it’s hard to know how stable the composition would be.”

Purna C. Kashyap, MBBS, of the Mayo Clinic in Rochester, Minnesota, who also wasn’t involved in the research, pointed out that the study lacked data on diet and other environmental factors that may drive changes in the microbiome. “The data are primarily correlational so it was unclear if the specific bacteria play a role in NAFLD.”

Study limitations included the assumption that the clinical characteristics and NAFLD risk factors of voluntary health-check-up patients were similar to those of the general population versus patients with established NAFLD or nonalcoholic steatohepatitis. In addition, a lack of histological data prevented further analysis on the relationship between gut and blood microbiota features and the severity of liver disease.

Also, the small number of NAFLD participants could have contributed to the absence of differences in diversity of blood and fecal microbiota, and the diagnosis of NAFLD by ultrasonography might also have influenced the number of cases owing to ultrasound’s limited sensitivity to detect hepatic steatosis, the authors pointed out.

last updated 03.19.2019