Having more diverse gut bacteria (greater microbiome richness) and specifically a greater abundance of 12 types of butyrate-producing bacteria were both associated with less insulin resistance and less type 2 diabetes, in a population-based observational study from the Netherlands.
Several studies have reported that there is less microbiome diversity in type 2 diabetes, Zhangling Chen, MD, PhD, of Erasmus Medical Center, Rotterdam, the Netherlands, and colleagues note.
Their study also identified a dozen types of bacteria that ferment dietary fiber (undigested carbohydrates) in the gut to produce butyrate, a short-chain fatty acid, which may play a role in protection against type 2 diabetes.
"The current study is the first, to our knowledge, to comprehensively investigate the associations between gut microbiome composition with type 2 diabetes in a large population-based sample for which we adjusted for a series of key confounders," the researchers write.
"These findings suggest that higher gut microbial diversity, along with specifically more butyrate-producing bacteria, may play a role in the development of type 2 diabetes, which may help guide future prevention and treatment strategies," they conclude in their study published online July 29 in JAMA Network Open.
Confirmation of Previous Work, Plus Some New Findings
The study confirms what many smaller ones have repeatedly shown — that low gut microbiome diversity is associated with increased risks of obesity and type 2 diabetes, Nanette I. Steinle, MD, RDN, who was not involved in the research, told Medscape Medical News in an interview.
A diet rich in fiber and prebiotics promotes gut biome diversity, added Steinle, chief of the endocrinology and diabetes section at Maryland Veterans Affairs Medical Center in Baltimore.
The findings add to other research, she noted, such as a prospective trial in which a high-fiber diet induced changes in the gut microbe that were linked to better glycemic regulation (Science. 2018;359:1151-1156) and a study of a promising probiotic formula to treat diabetes.
"An important next step," according to Steinle, "is to provide interventions like healthy diet or specific fiber types to see what can be done to produce lasting shifts in the gut microbiome and if these shifts result in improved metabolic health."
Natalia Shulzhenko, MD, PhD, said: "Some of associations of taxa [bacteria groupings] with type 2 diabetes reported by this study are new."
Shulzhenko and colleagues recently published a review of the role of gut microbiota in type 2 diabetes pathophysiology that summarized evidence from 42 human studies as well as preclinical studies and clinical trials of probiotic treatments (EBioMedicine. 2020;51:102590).
"Besides adding new microbes to the list of potential pathobionts [organisms that can cause harm] and beneficial microbes for type 2 diabetes," the findings by Chen and colleagues "support a notion that different members of the gut microbial community may have similar effects on type 2 diabetes in different individuals," commonly known as "functional redundancy," Shulzhenko, associate professor, Carlson College of Veterinary Medicine, Oregon State University, Corvallis, pointed out to Medscape Medical News in an email.
Also "in line with previous studies," the study shows that butyrate-producing bacteria are associated with type 2 diabetes.
She speculated that "these results will probably contribute to the body of knowledge that is needed to develop microbiota-based therapy and diagnostics."
Which Gut Bacteria Are Linked With Diabetes?
It is unclear which gut bacteria are associated with the development of type 2 diabetes, Chen and colleagues write.
To investigate this, they identified 1418 participants from the Rotterdam Study and 748 participants from the LifeLines-DEEP study enrolled from January 2018 to December 2020. Of these participants, 193 had type 2 diabetes.
The participants provided stool samples that were used to measure gut microbiome composition using the 16S ribosomal RNA method. They also had blood tests to measure glucose and insulin, and researchers collected other demographic and medical data.
Participants in the Rotterdam study were older than in the LifeLines Deep study (mean age, 62 vs 45 years). Both cohorts included slightly more men than women (58%).
Chen and colleagues identified 126 (bacteria) genera in the gut microbiome in the Rotterdam study and 184 genera in the LifeLines Deep study.
After correcting for age, sex, smoking, education, physical activity, alcohol intake, daily calories, body mass index, and use of lipid-lowering medication or proton pump inhibitors, higher microbiome diversity was associated with lower insulin resistance and a lower prevalence of type 2 diabetes.
A higher abundance of each of seven types of butyrate-producing bacteria — Christensenellaceae, Christensenellaceae R7 group, Marvinbryantia, Ruminococcaceae UCG005, Ruminococcaceae UCG008, Ruminococcaceae UCG010, and Ruminococcaceae NK4A214 group — was associated with lower insulin resistance, after adjusting for confounders such as diet and medications (all P < .001).
And a higher abundance of each of five other types of butyrate-producing bacteria — Clostridiaceae 1, Peptostreptococcaceae, C sensu stricto 1, Intestinibacter, and Romboutsia — was associated with less type 2 diabetes (all P < .001).
Study limitations include that gut microbiome composition was determined from stool (fecal) samples, whereas the actual composition varies in different locations along the intestine, and the study also lacked information about butyrate concentrations in stool or blood, the researchers note.
They call for "future research [to] validate the hypothesis of butyrate-producing bacteria affecting glucose metabolism and diabetes risk via production of butyrate."
The authors and Shulzhenko have reported no relevant financial relationships. Steinle has reported receiving funding from the National Institutes of Health and conducting a study funded by Kowa through the VA.
JAMA Netw Open. Published online July 29, 2021. Full text
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