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Type 2 diabetes is a complex condition, and research is ongoing about why the condition develops.
Researchers are interested in understanding how the gut microbiome affects type 2 diabetes.
A recent review highlighted existing literature on the gut microbiome and type 2 diabetes and explored how focusing on the gut microbiome could assist with diabetes management.
Diabetes affects over 38 million people in the United States alone. The vast majority of people who have diabetes have type 2 diabetes. Type 2 diabetes often involves involves insulin resistance, when cells in the body don’t respond well to the hormone insulin produced by the beta cells in the pancreas.
38 millio
beta cells
A paper published in Cell Host & Microbe reviewed how the gut microbiome affects the development of type 2 diabetes and its management. Paper authors further suggested how this information could be translated into clinical applications.
Cell Host & Microbe
Bharat Pothuri, MD, a gastroenterologist with Memorial Hermann Health System in Houston, TX, who was not involved in the study, said the evolving understanding of the gut microbiome beyond the context of gastrointestinal health could lead to new avenues for type 2 diabetes intervention.
Bharat Pothuri, MD
“Integrating microbiome-targeted therapies with conventional diabetes management could lead to more effective and holistic patient care,” he explained to Medical News Today.
“It should be noted that most of these studies were cross-sectional and not longitudinal as we do not have data gathered over an extended time period. We will need longer, prospective studies to have a better idea of the real efficacy of these proposed treatment options. Nevertheless, this leads to a promising and novel treatment approach to one of the world’s leading health problems,” he added.
How is the gut microbiome connected to type 2 diabetes?
The researchers of the current paper first note that type 2 diabetes is related to the dysfunction of the pancreas’ beta cells.
Recent research indicates that there are multiple pathways involved in the dysfunction of beta cells and that the gut microbiome can be part of this process. The authors note that this understanding has led to a more complex understanding of diabetes pathophysiology. For example, clinical data suggests that the gut microbiome affects the development of high blood sugar.
The gut microbiome refers to the microorganisms in the digestive tract, such as bacteria and viruses. The gut microbiome is involved in many systemic metabolic processes, and researchers are conducting more studies to understand its involvement in metabolic disease development.
The paper notes that many ancestral bacterial species have been lost over the years, leading to problems like metabolic diseases. There has been a decrease in gut microbiome diversity, likely related to medication use and Western lifestyle. The authors hypothesize that this lack of diversity in the gut microbiome is related to the increase in type 2 diabetes.
Previous research has noted the changes to the gut microbiome in people with type 2 diabetes, such as changes in bacteria proportions and declines in species diversity. Body responses, medications, and the Western diet can affect the gut microbiome. The paper even notes that oral antidiabetic medications can affect gut microbiota.
The gut microbiome further creates certain metabolism products that affect other body functions, like the immune system response and the gut barrier. Bile acids that are a metabolism product of the gut microbiome are affected in people with type 2 diabetes.
Thus, the authors emphasize that gut homeostasis is essential, even in people who already have type 2 diabetes and insulin resistance. They point to several studies that link type 2 diabetes with alterations to the gut microbiome.
However, they note that many of these studies used fecal samples, which does not show the heterogeneity of the GI tract. They then note that changes in the gut microbiome often lead to chronic inflammation, which further decreases gut microbiota.
Next, they note differences that occur in the gut microbiota’s metabolism products in individuals with type 2 diabetes and that these changes can impact the whole body.
They highlight the role of the gut microbiome in the “egregious eleven,” or the pathways that ultimately lead to beta cell dysfunction. They include information from many studies about how the gut microbiome metabolites likely and ultimately affect many organs in the body, like the pancreas, kidneys, and liver.
Finally, researchers note the relationship between oral medications to manage diabetes and the gut microbiome. They note that both affect each other.
For example, the gut microbiome is likely affected by antidiabetic drugs, and evidence suggests that metformin can improve the gut microbiome. Similarly, the gut microbiome can impact the effectiveness of antidiabetic medication. The cited evidence also suggests that the gut microbiome could explain some of the adverse effects of metformin use.
Paper author Abraham S. Meijnikman, MD, PhD, working at Amsterdam UMC, Experimental Vascular Medicine, and Tytgat Institute, noted the following to Medical News Today:
Abraham S. Meijnikman, MD, PhD
“The gut microbiota functions like an endocrine organ, influencing which nutrients are metabolized and absorbed. This interaction affects critical aspects of the egregious eleven, ranging from IR [insulin resistance] in the liver, muscle, and adipose tissue to the growth and function of the pancreas itself. Therefore, the composition of the gut microbiota plays a central role in type diabetes pathogenesis and management.”
Microbiome-centered therapies for treating diabetes
Based on the data that the paper authors presented, the researchers went on to suggest ways to target the gut microbiome to improve diabetes-related outcomes. For example, they cited evidence that using prebiotics and probiotics could benefit people with type 2 diabetes.
In addition, they also note evidence that supports the use of fecal microbial transplantation to improve diabetes outcomes. However, there were mixed results on the use of prebiotics and fecal transplants, and more research may be required to look into these and the use of combined pro and prebiotics, which are called synbiotics.
They further underscore that there is a lot of variation in gut microbiomes in people with type 2 diabetes, which suggests the need for individualized approaches.
Meijnikman noted the three following clinical implication areas:
“1. Personalized treatment plans: Developing personalized treatment strategies based on a patient’s gut microbiota profile. This could include tailored dietary recommendations, specific probiotic or prebiotic supplements, and possibly FMT [fecal microbial transplantation] to restore healthy gut microbiota.
2. Microbiota modulation: Integrating gut microbiota modulation into existing treatment plans for T2DM, such as adjusting medication based on how it interacts with the patient’s microbiota to enhance efficacy and reduce side effects.
3. Diagnostic tools: Utilizing advanced diagnostic tools that analyze a patient’s gut microbiota to predict disease progression and treatment response, thereby enabling more targeted and effective interventions.”
Review limitations
This review highlighted some available data on the gut microbiome and type 2 diabetes. However, there are limitations that emphasize the need for more research.
First, some studies cited involved work with mice and highlight the need for more research with people. When looking at antidiabetic medications and the gut microbiome, the paper authors cited many studies on metformin, so future research could include other oral diabetes medications and look even more at the complex relationship between these medications and gut microbiome.
Mejdi Ahmad, MD, a board-certified gastroenterologist with Medical Offices of Manhattan, who was not involved in the study, also noted that “future longitudinal research needs to be done to offer better-guided microbiota-based therapies to tackle gut biome associated clinical conditions. How we modify the gut biome with drugs needs to be evaluated in research trials in order to reach a better understanding of drug bioavailability and efficacy in this realm.”
Mejdi Ahmad, MD
Medical Offices of Manhattan
All studies and sources noted in this paper had limitations, some were weaker, and others did not support the author’s overall claims. For example, the authors note that some studies have not done appropriate covariate control, which could have impacted results.
In addition, many studies have relied on fecal sampling, so it may be important to look at the composition of the whole GI tract in people with type 2 diabetes. The authors of the paper note that research can include more longitudinal studies to help establish causality and data to figure out how to develop microbiota-targeted therapies. The data can also examine how altering the gut microbiome could affect long-term prevention and treatment.
Thus, there is still room for confirming previous research and examining the clinical implementation of some of these ideas.
Meijnikman noted that further research could include “Long-term clinical trials to assess the efficacy and safety of microbiota-targeted therapies, such as FMT, probiotics, and prebiotics, in preventing or managing T2DM… and research aimed at refining personalized medicine approaches based on microbiota profiles, including developing new therapeutic agents that can modulate gut microbiota more precisely.”