Gut bacteria may play a role in diabetes
Abstract: People with higher levels of the gut bacteria Coprococcus have higher insulin sensitivity, while those with higher levels of Flavonifractor have lower levels of insulin sensitivity. Researchers say that specific gut bacteria may play a significant role in the development of type 2 diabetes.
Source: Cedars Sinai Medical Center
One type of bacteria found in the gut may contribute to the development of type 2 diabetes, while another may protect against the disease, according to the first results of an ongoing prospective study led by Cedars-Sinai researchers.
The study, published in a peer-reviewed journal Diabetesfound that people with higher levels of a bacteria called Coprococcus had higher insulin sensitivity, while those whose microbiomes had higher levels of the Flavonifractor bacteria had lower insulin sensitivity.
For years, researchers have tried to understand why people develop diabetes by studying the composition of the microbiome, which is the collection of microorganisms that include fungi, bacteria and viruses that live in the digestive tract.
The microbiome is thought to be influenced by drugs and diet. Studies have also found that people who do not process insulin properly have lower levels of a certain type of bacteria that produces a type of fatty acid called butyrate.
Mark Goodarzi, MD, Ph.D., director of the Endocrine Genetics Laboratory at Cedars-Sinai, is leading an ongoing study that is tracking and observing people at risk for diabetes to see if those with lower levels of these bacteria develop the disease.
“The big question we hope to address is: Did the differences in the microbiome cause the diabetes or did the diabetes cause the differences in the microbiome?” said Goodarzi, who is senior author of the study and principal investigator of a multicenter study called the Microbiome and Insulin Longitudinal Evaluation Study (MILES).
As of 2018, investigators involved in MILES have been collecting information from participating black and non-Hispanic white adults between the ages of 40 and 80. An earlier cohort study from the MILES trial found that cesarean birth was associated with a higher risk for developing prediabetes and diabetes.
For the latest study that emerged from this ongoing trial, researchers analyzed data from 352 people without known diabetes who were recruited from Wake Forest Baptist Health System in Winston-Salem, North Carolina.
Study participants were asked to attend three clinic visits and collect stool samples prior to the visit. The researchers analyzed the data collected during the first visit. They conducted genetic sequencing of stool samples, for example, to study the participants’ microbiomes and specifically look for bacteria that earlier studies had found to be associated with insulin resistance.
Each participant also completed a dietary questionnaire and underwent an oral glucose tolerance test, which was used to determine the ability to process glucose.
The researchers found that 28 people had oral glucose tolerance test results that met criteria for diabetes. They also found that 135 people had prediabetes, a condition in which a person’s blood sugar levels are higher than normal but not high enough to meet the definition of diabetes.
The research team analyzed the association between 36 butyrate-producing bacteria found in stool samples and a person’s ability to maintain normal insulin levels. They controlled for factors that may also contribute to a person’s diabetes risk, such as age, sex, body mass index and race. Coprococcus and related bacteria formed a network of bacteria with beneficial effects on insulin sensitivity.
Despite being a butyrate producer, Flavonifractor has been associated with insulin resistance; previous work by others found higher levels of Flavonifractor in the stool of people with diabetes.
The researchers are continuing to study samples from patients who participated in this study to learn how insulin production and microbiome composition change over time. They also plan to study how diet can affect the bacterial balance of the microbiome.
However, Goodarzi emphasized that it is too early to know how people can change their microbiome to reduce their risk of diabetes.
“As for the idea of taking probiotics, that would really be somewhat experimental,” said Goodarzi, who is also the Eris M. Field Chair for Diabetes Research at Cedars-Sinai.
“We need more research to identify the specific bacteria we need to modulate to prevent or treat diabetes, but it’s coming, probably in the next five to ten years.”
About this microbiome and diabetes research news
Original research: Open access.
“Butyrate-producing bacteria and insulin homeostasis: the Microbiome and Insulin Longitudinal Evaluation Study (MILES)” Jinrui Cui et al. Diabetes
Butyrate-producing bacteria and insulin homeostasis: the Microbiome and Insulin Longitudinal Evaluation Study (MILES)
Gut microbiome studies have documented a reduction in butyrate-producing taxa in type 2 diabetes. We analyzed associations between butyrate-producing taxa and detailed measures of insulin homeostasis, the dysfunction of which underlies diabetes in 224 non-Hispanic and 129 African-American subjects, all of whom completed oral glucose tolerance test. The stool microbiome was assessed by whole metagenome sequencing with taxonomic profiling.
We examined the relationship between 36 taxa that produce butyrate (n = 7 genera and 29 species) and insulin sensitivity, insulin secretion, disposition index, insulin clearance, and prevalence of dysglycemia (prediabetes plus diabetes, 46% of the cohort), adjusted for age, sex, BMI, and race.
Gender Coprococcus was associated with greater insulin sensitivity (β = 0.14; P = 0.002) and disposition index (β = 0.12; P = 0.012) and a lower rate of dysglycemia (odds ratio [OR] 0.91; 95% CI 0.85–0.97; P = 0.0025).
In contrast, Flavonifractor was associated with lower insulin sensitivity (β = -0.13; P = 0.004) and disposition index (β = −0.11; P = 0.04) and higher prevalence of dysglycemia (OR 1.22; 95% CI 1.08–1.38; P = 0.0013). Species-level analyzes found 10 bacteria associated with beneficial pathways and two bacteria with unfavorable links to insulin homeostasis and dysglycemia.
Although the majority of butyrate producers analyzed appear to be metabolically beneficial, this is not the case for all such bacteria, suggesting that microbiome-targeted therapeutics to prevent or treat diabetes should target specific butyrate-producing taxa rather than all butyrate producers.