Obesity and metabolic disease are complex diseases that result from interaction of genetic and environmental factors. Over the past decade, gut microbiota have been suggested to be an important contributor to the development of obesity and metabolic disease.
Microbiota have also been shown to be associated with obesity-related comorbidities such as type 2 diabetes (T2D) and metabolic diseases such as hypertension and dyslipidemia. Modulation of microbiota can reduce metabolic syndrome disorders, suggesting an association between specific microbial composition and metabolic phenotype.
No previous study has evaluated differences in microbiota between metabolically healthy (MH) and metabolically unhealthy (MU) overweight and obese individuals, even though obesity and metabolic syndrome share a range of phenotypes and interactions between genetic risk factors and environmental influences, including the gut microbiota. Debate over the disease risk associated with MHO continues, and there is a lack of understanding of the mechanisms that underlie MHO. For this reason,the current study investigated the composition of gut microbiota according to metabolic health status in obese and overweight subjects.
A total of 747 overweight or obese adults were categorised by metabolic health status, and their fecal microbiota were profiled using 16S ribosomal RNA gene sequencing. They were classified into a metabolically healthy group (MH, N = 317) without any components of metabolic syndrome or a metabolically unhealthy group (MU, N = 430) defined as having at least one metabolic abnormality.
The resulting data indicate that phylogenetic and non-phylogenetic alpha diversity for gut microbiota were lower in the MU group than the MH group, and there were significant differences in gut microbiota bacterial composition between the two groups.
The genus Oscillospira and the family Coriobacteriaceae were associated with good metabolic health in the overweight and obese populations. The researchers therefore argue modulation of the gut microbiome may help prevent metabolic abnormalities in the obese population.
A number of limitations to the study are listed, including the fact it only included individuals drawn from the Korean population, and the use of 16S rRNA gene sequencing, which provides limited information about bacterial genes and their functions.
Among the total of 747 subjects, 317 (42.4%) were in the MH group and 430 (57.6%) in the MU group. MH subjects were more likely to be younger and have a lower body mass index (BMI) than MU subjects. All metabolic indicators except total cholesterol, LDL cholesterol, and hsCRP were significantly higher in the MU group. Age, BMI, and weight were higher in MU group.
To control for covariates, the researchers constructed two models using generalised linear modeling. First, they analysed crude associations without adjustment, and then they controlled for age, sex, and BMI.
At the genus level, Oscillospira within the family Ruminococcaceae and Clostridium within the family Clostridiaceae were significantly more abundant in metabolically healthy subjects. Some Oscillospira species can likely secrete important short chain fatty acids (SCFAs) which are a source of energy for the host and can produce a signal through membrane receptors to integrate metabolic functions.
SCFAs have beneficial effects on body weight control, inflammatory status, and insulin sensitivity, as well as glucose and lipid homeostasis.
Clostridium is a butyrate-producing bacterium. Previous studies showed a significant decrease in butyrate-producing bacteria, including Clostridium, in individuals with type 2 diabetes mellitus (T2DM) compared to healthy individuals. These results suggest that butyrate-producing bacteria afford protection against T2DM. Butyrate also improves colon mucosal barrier function, exhibits immunomodulatory effects and exhibits anti-inflammatory properties by downregulating pro-inflammatory cytokines.
The family Coriobacteriaceae of Actinobacteria and Leuconostocaceae of Firmicutes were more abundant in the MH group than in the MU group. The family Coriobacteriaceae is known to perform important metabolic functions such as conversion of bile acid, steroids, and phytoestrogens, and this family has been investigated in the context of metabolic diseases. Bacteria have also been reported to play important roles in the onset and maintenance of fatty liver disease.
With the exception of the species Eggerthella lenta, one or more members of the family Coriobacteriaceae are considered potential contributors to various biological host functions such as glucose homeostasis and bile acid and lipid metabolism, suggesting that the increased presence of Coriobacteriaceae in the MH group may be beneficial. The family Leuconostocaceae comprise lactic acid bacteria (LAB) belonging to the order Lactobacillales; this family was abundant in the MH group. In our previous study, we found a negative association between the family Leuconostocaceae and obese individuals with NAFLD but not lean individuals with NAFLD or all individuals with NAFLD.
The researchers also observed an increased abundance of Fusobacteria in the MU group, including lower taxa levels. A majority of studies have reported that the Fusobacteria and sub-taxa are enriched in intestinal inflammation.
Interestingly, the team also found that pathways related to lysine and glycogen biosynthesis were highly upregulated in the MH group compared with the MU group. In a previous study, lysine level was decreased in nascent metabolic syndrome patients and was negatively correlated with inflammatory biomarkers and cardio-metabolic parameters.