Gut Microbiota & Risk Assessment for Type 2 Diabetes

Can the diurnal signatures of gastrointestinal microbiota reveal predispositions to diseases such as type 2 diabetes? 

A new study suggests that the risk of diabetes can be determined by analyzing changes in gut bacteria. We know that lifestyle, obesity, and genetic predispositions play a role in metabolic disorders. However, new insight has led researchers to believe that the gut microbiome is just as important. Reitmeier et al. described how the relative abundance of gut bacteria’s rhythmic oscillations differs in patients with type 2 diabetes mellitus (T2DM). This finding led to a new study aimed at determining the predictive value of bacterial signatures in T2DM.   

The human gut is a complex environment with trillions of organisms and thousands of bacterial taxa forming the healthy microbiota. These organisms start symbiotic relationships with their host by defining the mucosal immune system, maintaining epithelial barrier function, producing essential vitamins, and fermenting or digesting substances that humans cannot. Microbial DNA represents over 100-fold-more genes than the human genome. Given the large amount of genetic information stored within these organisms, one could suspect there may be more to this relationship than has yet been discovered.  

Several studies have shown associations between microbiota diversity and metabolic health. Reduced or altered gastrointestinal biodiversity has been linked to obesity and other metabolic diseases. We know that diet is an essential modulator in the gastrointestinal ecosystem, and there is evidence that gut microbiota can shift in as little as two days of changing diet. However, some studies suggest that the microbiome composition is determined by long-term dietary trends, despite the rapid responses seen in individual microorganisms.  

Both animal and human studies have shown that gut bacteria follow a circadian rhythm in terms of number and function. The circadian clock is responsible for synchronizing sleep-wake cycles, along with food intake behavior and metabolism. Recently, it has been proposed that this rhythm may also play a role in microbial homeostasis. Because there seems to be a link between the gut microbiome and metabolic health, researchers believe there may be a way to identify patients at risk for T2DM based on their diurnal microbial signatures.  

The study published in Cell Host and Microbe explored the link between metabolic pathways and diurnal oscillations of gut bacteria. Fecal samples were collected from the participants of various large population-based cohorts across Germany and England. Any patients with gut-related diseases were excluded from the analysis. The samples were sequenced using high-throughput 16S rRNA gene amplicon sequencing, then analyzed to identify the diversity and abundance of bacteria in a fixed 24-hour period.  

Variations in the microbiota of less than 1% were observed between cohorts in different geographical regions. Individuals with the lowest microbial diversity had higher relative abundances of Bacteroides species, while those with the highest diversity had higher relative abundances of species in the genus, Ruminococcus.  Different microbial taxa dominated the microbiota at varying times of the day. Among the microorganisms that showed diurnal rhythmicity were two of the most dominant species, Bacteroidetes (highest at night) and Firmicutes (highest during the day).  

Patients with T2DM and obesity showed lost or reduced microbial oscillations compared to healthy individuals. Species richness and diversity were significantly lower in this population as well. Individuals with pre-diabetes have also demonstrated reduced oscillating species compared to healthy subjects. The species that lost rhythmicity in patients with T2DM belonged to the genera Akkermansia, Bacteroides, Bifidobacterium, Blautia, Clostridium, Coprococcus, Dorea, Prevotella, Roseburia, and Ruminococcus.  

Many of these also lost rhythmicity in pre-diabetes. The analysis showed that eating behaviors and dietary intake did not account for any differences in microbial shifts between people with T2DM and those without. Of the species that lost rhythmicity in people with diabetes, 63 were consistently predictive upon analysis. This signature included Bifidobacterium longum, Clostridium celatum, Intestinibacter bartlettii, Romboutsia ilealis, and several taxa closely related to Fecalibacterium prausnitzii, and Escherichia coli.  

In these population-based cohorts, arrhythmic bacteria were considered markers for potential disease. These markers were referred to as risk signatures. Knowing this information can potentially improve the diagnosis and outlook of type 2 diabetes. Although much of the gut microbiome is well established early in life and is thought to remain relatively stable throughout adulthood, some studies suggest that it can be altered with diet, lifestyle modifications, and medications. The study did highlight a significant degree of variability in inter-individual microbiomes. Also, missing, incomplete, or misreported data may have resulted in differences between groups. Therefore, a combination of food-questionnaires and objective biomarkers could make for a more robust study in the future. Altogether, these population-based findings support the need further to research the association between gut bacteria rhythmicity and T2DM. 

Practice Pearls: 

• The human gut microbiome exhibits a rhythmic pattern across regions and populations. 
• Individuals that have obesity or type 2 diabetes show disrupted circadian rhythms in gut microbiota. 
• T2DM has been successfully predicted in patients with arrhythmic bacterial signatures. 

References for “Gut Microbiota & Risk Assessment for Type 2 Diabetes”:

Reitmeier S, Kiessling S, Clavel T, et al. Arrhythmic Gut Microbiome Signatures Predict Risk of Type 2 Diabetes  

Sonnenburg JL, Bäckhed F. Diet-microbiota interactions as moderators of human metabolism. Nature. 2016;535(7610):56-64. doi:10.1038/nature18846 

Jensen ET, Bertoni AG, Crago OL, et al. Rationale, Design, and Baseline Characteristics of the Microbiome and Insulin Longitudinal Evaluation Study (MILES) [Diabetes Obes Metab.] 

Melinda Rodriguez, PharmD Candidate 2021, Lake Erie College of Osteopathic Medicine – L|E|C|O|M School of Pharmacy 

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