Date Submitted: 2/19/2025
Date Accepted: 3/12/2025
What is diabetes?
Type 2 Diabetes Mellitus (T2DM) is a medical condition where patients have high blood sugar levels due to the body’s inability to respond effectively to insulin. Insulin is the hormone responsible for regulating glucose levels in the bloodstream. Glucose is the basic sugar food is broken down into. Insulin works as a negative feedback mechanism, lowering blood glucose levels when they are too high. T2DM causes symptoms such as increased thirst, frequent urination, fatigue/tiredness, blurred vision, and slow healing wounds.
T2DM, also known as adult-onset diabetes, is a prevalent global health problem that is only growing. In fact, it has been estimated that 1 in 14 adults in the United States, and 1 in 9 adults in the UK have prediabetes, and that by the year 2030, 7,079/100,000 adults will have T2DM (1).
Some patients may be pre-diabetic, meaning that blood sugar levels are higher than normal, but not high enough to be classified as T2DM. We have just described T2DM and prediabetes, but Type 1 Diabetes (T1DM) is a condition where the body’s pancreas, the organ responsible for producing insulin, produces little to no insulin resulting in high blood glucose levels. T1DM is classified as an autoimmune disease and is often inherited, and is usually diagnosed during childhood.
However, T2DM is developed mainly through lifestyle and is usually diagnosed in adulthood. For T2DM it is important to be diagnosed early because if untreated, complications from T2DM are devastating. Complications include heart disease, stroke, kidney disease, nerve damage, and foot ulcers. It is important to talk to a doctor to determine which type of diabetes you have, as the treatment plans are different.
What is a gut microbiome?
The human gut, which includes the stomach, small intestine, and large intestine, has a large population of bacteria, yeast, fungi, and other microbes. These elements produce chemicals that help the body digest food, form an immune response, and carry out other bodily functions such as metabolism, inflammation prevention, and strengthening the gut barrier.
The microbiome contains yeasts, fungi, parasites, and viruses as well, but bacteria are the most abundant and best studied; this is why bacteria are specifically used to measure gut health. The composition of our gut microbiome is shaped by our genetic background, environment, and most importantly diet (2). The balance in our microbial ecosystem is deemed crucial due to its many functions. The idea of having more beneficial bacteria, and a minimal amount of pathogenic species is a key factor in maintaining our health (3). Ilya Mechnikov, who is known as the father of natural immunity, also mentioned that a lot of disease begins when ‘good’ bacteria are no longer able to control the ‘bad’ ones (1).
The gut microbiome is one of the most significant fields that needs further investigation due to its potential to serve as a predictor for diseases like diabetes.
During recent studies of microbiomes, researchers were able to associate the microbes with either eubiosis (positively affecting our health) or dysbiosis (disrupting the homeostasis of our health )(4).
Some bacteria in our gut called butyrates use fiber to go through fermentation. As a result, they produce Short Chain Fatty Acids (SCFAs). SCFAs are essential to a healthy gut, as they reduce inflammation, lower blood pressure and cholesterol levels, boost immune function, and regulate metabolism and appetite (5). So, having a healthy population of butyrates is important.
The bacteria in our gut can be categorized into a taxonomic tree, showing their evolutionary relationships with other bacteria. So, it is more beneficial to study bacteria on a more specific level.
In studying the microbiome, most taxonomic studies are conducted on a phylum or genera levels (6). Phylum is the third broadest category in the taxonomic hierarchy, helping in identifying the general microbial trend. For instance, Proteobacteria and Enterobacteriaceae, two phyla commonly found in our gut, are known to be more abundant among diabetic individuals (1). And by studying on a more specific genera-level, we are able to associate the microbes with a certain disorder, like Akkermansia muciniphila, a bacterium within the phylum Verrucomicrobia, to our gut health and insulin sensitivity (7). But scientists are realizing that this taxonomic information is often not enough, which is why they are leaning towards studying microbiomes on a lower and more specific taxonomic level for higher accuracy.
An important addition to the research on microbial bacteria associated with T2DM is the review paper titled “Understanding Patterns of the Gut Microbiome May Contribute to the Early Detection and Prevention of Type 2 Diabetes Mellitus: A Systematic Review.” The purpose of this paper is to establish common microbial patterns in the prediabetic or T2DM gut microbiome.
The paper gathered information on bacteria that were associated with T2DM. Papers with similar design, analytic protocol, and data using Illumina sequencing technology were collected. Specifically, studies that utilized stool analysis in sampling the gut microbiome or evaluated treatment groups with both untreated T2DM and non-diabetic controls were selected. Ultimately, a total of 21 articles and reviews published between 2010 and 2024 were chosen for this review.
By comparing the gut microbiome compositions of patients with and without T2DM, we can determine which types of bacteria are positively and negatively correlated with diabetes. A negative correlation means that diabetic patients generally have less of these types of bacteria than a healthy patient. The bacteria with a negative correlation across all studies include Akkermansia spp., Ruminococcae, Faecalibacterium spp., Clostridiaceae, Bifidobacterium spp. and Bacteroides spp. However, some bacteria have a positive correlation, meaning diabetic patients have more of these types of bacteria compared to a healthy patient. The bacteria with a positive correlation across all studies include Shigella, Escherichia, and Ruminococci.
While some studies assessed in this review had consistent results, some had conflicting findings to be aware of. Most studies determined that pre-diabetic and T2DM patients had overall lower bacteria diversity. Some studies showed that diabetic patients present with an increase in Lactobacillae, Dorea, Lachnospiracea, and Proteobacteria phylum, but some did not have the same findings, representing a need to further study these bacteria.
It is also important to know that some medications change the results of the tests. For example, many patients with T2DM are prescribed Metformin, a medication that manages high blood sugar by enhancing insulin sensitivity and decreasing glucose absorption in the intestines (8). It is possible that Metformin leads to increases in Blautia and Anaerostipes in some studies. Overall, there were 20 bacterial taxa reported as discrepant across studies including Faecalibacterium which was very contradictory.
This review paper further confirmed correlations between the gut microbiome and T2DM, and emphasized which associations of certain bacteria were consistent across different studies, and which were not. Specifically, this paper focused on including research from all over the world and at lower taxonomic levels than what is usually focused on.
It is important to note that microbiome research involves a multitude of confounding factors including varying demographics, living conditions, diets and health conditions of the participants, and variations in methodology. Due to these limitations as well as the nature of using a cross-sectional design for microbiome research, we are unable to infer causality between the microbiome and T2DM. However, it has been theorized that the causality could be explained by shortages in Clostridiacea class depleting the secretion of glucagon-like peptides, which is linked to the decreased production of SCFAs (1).
Future research is needed to address some of the limitations listed above, and better identify which bacteria have positive and negative correlations, considering the large inconsistencies this paper identified. Researchers should continue to use Illumina sequencing to maintain consistency and reliability. The goal would be to potentially one day use the presence of certain bacteria as a detection marker for diabetes risk, and guide interventions to mitigate this risk or treatment options. The development of early-detective and preventive measures would be crucial in efforts towards lowering the prevalence of T2DM.
About The Authors
Authors (alphabetical by last name): (name, email, university affiliation)
Yoonseop (Ryan) Choi: choiryan23@gmail.com, UC San Diego
Lia Florio: lef9179@nyu.edu, New York University
Nashwan Osman: nashyosman@gmail.com, Washington University in St. Louis
Rachel Tran: tran.rachelk@gmail.com, University of Georgia
Eric Zhou: ericzhou246@g.ucla.edu, University of California, Los Angeles
References:
Bednarska NG, Håberg AK. Understanding Patterns of the Gut Microbiome May Contribute to the Early Detection and Prevention of Type 2 Diabetes Mellitus: A Systematic Review. Microorganisms. 2025;13(1):134. Published 2025 Jan 10. doi:10.3390/microorganisms13010134
Bibbò, S., Ianiro, G., Giorgio, V., Scaldaferri, F., Masucci, L., Gasbarrini, A., & Cammarota, G. (2016). The role of diet on gut microbiota composition. European review for medical and pharmacological sciences, 20(22), 4742–4749.
Li WZ, Stirling K, Yang JJ, Zhang L. Gut microbiota and diabetes: From correlation to causality and mechanism. World Journal of Diabetes. 2020 Jul 15;11(7):293–308.
Iebba V., Totino V., Gagliardi A., Santangelo F., Cacciotti F., Trancassini M., Mancini C., Cicerone C., Corazziari E., Pantanella F., et al. Eubiosis and dysbiosis: The two sides of the microbiota. New Microbiol. 2016;39:1–12.
Xiong, R. G., Zhou, D. D., Wu, S. X., Huang, S. Y., Saimaiti, A., Yang, Z. J., Shang, A., Zhao, C. N., Gan, R. Y., & Li, H. B. (2022). Health Benefits and Side Effects of Short-Chain Fatty Acids. Foods (Basel, Switzerland), 11(18), 2863. https://doi.org/10.3390/foods11182863
Lozupone C.A., Stombaugh J.I., Gordon J.I., Jansson J.K., Knight R. Diversity, stability, and resilience of the human gut microbiota. Front. Microbiol. 2020;11:2029.
Mohr A.E., Jäger R., Carpenter K.C., Kerksick C.M., Purpura M., Townsend J.R., West N.P., Black K., Gleeson M., Pyne D.B., et al. The athletic gut microbiota. J. Int. Soc. Sports Nutr. 2020;17:24. doi: 10.1186/s12970-020-00353-w.
MedLine Plus. Metformin: MedlinePlus Drug Information [Internet]. Medlineplus.gov. 2020. Available from: https://medlineplus.gov/druginfo/meds/a696005.html
Nice work!