New discovery | Intestinal flora affects obesity!

Obesity is a global public health issue. Some studies predict that by 2030, the number of obese people in the world will reach 1.12 billion. Obesity not only changes one's appearance, but is also an important risk factor for diseases such as metabolic syndrome (MS) and diabetes. Gut microbiota maintains a symbiotic relationship with the host, affecting the body's nutrition, metabolism, inflammatory response, etc. Many studies have confirmed that gut microbiota is closely related to metabolic diseases.

But is it metabolic disease caused by intestinal flora disorder? Or is it metabolic disease that causes intestinal flora disorder? The causal relationship between the two is not clear.

Recently, a study published in The Lancet Diabetes and Endocrinology reported a large cross-sectional study in Norway, which confirmed that Ruminococcus Gnavus (Rg) in the intestinal flora is associated with multiple metabolic syndrome characteristics, and body mass index (BMI) and C-reactive protein do not affect Ruminococcus, and there is no reverse causal relationship. These findings provide insights into predicting or treating metabolic diseases through the abundance of intestinal flora.

Screenshot from: The Lancet Diabetes and Endocrinology

The researchers distributed questionnaires and stool collection tools to 55,561 people, and ultimately collected 13,268 valid copies, which were divided into a discovery cohort (n=2875) and two replications (n=999 and n=1341). The focus was on observing whether there was any correlation between the 50 common intestinal microorganisms and body fat percentage, as well as the possible causal relationship between them.

Alpha diversity and beta diversity are commonly used indicators for evaluating microbial ecology. A higher alpha diversity indicates a greater number of species in the community, while beta diversity indicates the number and distribution of species in different communities. The results showed that in the discovery cohort of 2,875 people, the alpha diversity of the microbial community was negatively correlated with body fat percentage, that is, the higher the body fat percentage, the lower the alpha diversity of the microbial community. A study on the intestinal flora metagenomics and serum metabolomics of obese or normal-weight subjects in the Chinese population also came to a similar conclusion, finding that the alpha diversity of the microbial community in obese subjects was reduced, while the beta diversity was increased.

Figure 1: Alpha and beta diversity in subjects in the discovery cohort (screenshot from reference [7])

This study also determined that the relative abundance of 11 microorganisms was correlated with body fat percentage. It can be seen that Ruminococcus had the strongest correlation with body fat percentage, and this association was also verified in two other independent cohorts.

▲Figure 2: The relative abundance of microorganisms in the cohort was found to be correlated with body fat percentage (screenshot source: reference [7])

Considering that intestinal microorganisms are easily affected by confounding factors such as age, gender, diet, drinking, and medication, the researchers this time specifically corrected for confounding factors such as chronic diseases and medications, and found that the correlation still exists.

Figure 3: Relationship between relative abundance of Ruminococcus and body fat percentage before and after adjustment for confounding factors (Screenshot source: Reference [7])

Previous studies have shown that high fat is associated with metabolic syndrome and inflammatory response. Does Ruminococcus play a related role?

The researchers selected fat mass, body mass index, waist circumference, C-reactive protein (CRP), triglycerides, etc. as indicators and found that they were all associated with Ruminococcus.

The final results of the Mendelian randomization analysis showed that body mass index and C-reactive protein did not affect live Ruminococci, and there was no reverse causality. In other words, it was the abundance of Ruminococci that caused changes in body mass index and C-reactive protein.

▲Figure 4: Two-sample Mendelian randomization analysis of the relationship between BMI and CRP as exposure and Ruminococcus as outcome (screenshot source: reference 7)

In addition, the genetic risk score (GRS) of Ruminococcus and body mass index can independently and additively predict metabolic traits such as fat mass. Compared with people without Ruminococcus and a genetic risk score of body mass index below the median, people with Ruminococcus and a genetic risk score of body mass index above the median had 4.8 kg more fat. Moreover, Ruminococcus was more strongly associated with triglycerides and C-reactive protein.

Figure 5: Genetic risk scores for Ruminococcus and body mass index are independent and additive predictors of body fat percentage (screenshot source: reference [7])

However, this study did not use deep metagenomic sequencing to mine specific genes, pathways, and rumen cocci strains associated with metabolic syndrome, and further research is needed. The research team hopes that future studies can explore whether rumen cocci can predict cardiometabolic diseases and whether the related pathways of this flora can be used as therapeutic targets for metabolic diseases.

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