The first signs of a community of microbial cells — mostly bacteria — living primarily in our upper and lower intestines microbiome were discerned over a century ago.
The term “microbiome” was coined only in 2009 by Joshua Lederberg. We remain in the early days of our understanding of this complicated microbial terrain.
Now, a new study from researchers at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan reports the discovery of an order of gut bacteria that may help protect against type 2 diabetes and obesity by improving insulin resistance. The bacteria are Alistipes indistinctus.
The researchers also identified bacteria from the order Lachnospiraceae that are more commonly present in the stools of people with insulin resistance, versus those without insulin resistance. This suggests it may be a helpful biomarker of the condition.
The study appears in the journal Nature.
The researchers analyzed stool samples taken at regular checkups of 306 healthy individuals from 20 to 75 years of age, with the average age being 61. Of this group, 71% were male, and none had diabetes.
The contents of their stools were cross-referenced with the individuals’ insulin-resistance levels.
It turned out that people with excessive carbohydrates — monosaccharides such as glucose, fructose, galactose, and mannose — in their fecal matter were more likely to have insulin resistance.
Looking closely at the bacterial inhabitants of the samples, the researchers found greater numbers of Lachnospiraceae bacteria in people with insulin resistance, as well as in people with the telltale monosaccharides in their stool.
Conversely, people whose feces contained more Bacteroidales-type bacteria — as opposed to Lachnospiraceae — had lower insulin resistance, and a smaller number of monosaccharides in the gut.
The authors feel that the major strength of their investigation is the cataloging of 2,800 annotated fecal metabolites combined with microbiome and host pathology.
Metabolites are small molecules that are the byproducts of cell metabolism, and can provide chemical clues as to the cells that produced them during metabolization.
This process allowed the researchers to identify metabolites related to insulin resistance, pinpoint associations between fecal carbohydrates and low-grade insulin resistance inflammation, and thus select candidates for validation in mouse experiments.
“There have been some studies showing the association of gut microbes with obesity or insulin resistance in humans,” noted Dr. Hiroshi Ohno, team leader at the RIKEN Center, and one of the study authors.
“For example, Alistipes has been shown to decrease in obese individuals. However, these studies failed to reveal the causal relationship between those microbes and obesity,” he told Medical News Today.
“By combining metabolome analysis and animal experiments, we proved the causal relationship and that oral administration of Alistipes can protect from insulin resistance,” he said.
Asked if his team had further plans for their 2,800 metabolites, Dr. Ohno responded: “We focused more on hydrophilic metabolites [metabolites that mix with water] in this study. We would like to investigate hydrophobic/lipidomic metabolites, which also include interesting metabolites associated with insulin resistance/sensitivity in our preliminary analysis, in the future.”
Although the authors point out that there are currently no probiotics available that contain A. indistinctus, that may one day change with further validation of this research.
As far as the biomarker of insulin resistance Lachnospiraceae goes, Dr. Ohno suggested: ”One possibility is to identify Lachnospiraceae-specific bacteriophages and/or endolysins. They could lyse [destroy] Lachnospiraceae strains if they can be applicable for use in humans.”
The role of monosaccharides is ‘surprising’
The presence of the monosaccharides in the individuals’ stools is a surprise, said gastroenterologist Dr. Ashkan Farhadi, who was not involved in the study.
“I think that, up to now, we thought everything absorbable is already absorbed by the time things get to the colon,” he noted.
According to Dr. Ohno, the source of these carbohydrates is dietary fibers, or polysaccharides that are normally broken up by gut bacteria.
However, Dr. Ohno hypothesized that “[w]hen you have more Lachnospiraceae in your colon, the probability is high for more monosaccharide production by those microbes that results in higher fecal monosaccharides.”
He noted that monosaccharides cannot come from inside the human body to the intestinal tract, so it is unlikely insulin is involved in the presence of high levels of monosaccharides in feces.
How bacteria help regulate metabolism
Dr. Farhadi noted: “Our understanding of the role of gut bacteria is getting deeper, but it still is not even at the surface. It’s really a very shallow understanding of what they [the bacteria] are doing.”
“There were many other studies,” said Dr. Farhadi, “that show that we can transfer obesity from an obese animal to a lean animal by transferring the bacteria. But this is the first study that put a little bit more detail into the evidence.”
“So I think it’s a huge leap forward for our understanding that these gut germs have more hands in our body and its function, and particularly now in metabolism.”
– Dr. Ashkan Farhadi