Host-Microbe Composition in Prediabetes and Type 2 Diabetes 

Patients with prediabetes show differences in human host markers and gut microbiome compared to healthy patients. 

Type 2 diabetes is a fast-growing disease among millions of people worldwide. Before developing type 2 diabetes, patients are in the stage known as prediabetes, considered hyperglycemia, which can lead to type 2 diabetes if healthier lifestyle modifications are not initiated. Prediabetes and type 2 diabetes happen when patients are resistant to insulin, meaning their bodies produce insulin but their cells do not respond to the insulin to be uptaken into the cells for energy. This mechanism that causes type 2 diabetes in its’ earliest stage is associated with the body’s biological processes and overall health.  

Researchers have investigated that patients with prediabetes show differences in human host markers and gut microbiome compared to healthy patients. Physiological stresses, such as viral infections, can also contribute to the onset of diabetes. Researchers are unsure how healthy patients and those with prediabetes differ at baseline or change over time due to individual responses to stress or responses dependent upon insulin-resistance status.  

A longitudinal analysis was conducted to understand better the biological processes of healthy patients and those in the earliest stages of type 2 diabetes when dealing with glucose impairment. The study examined the human gut and nasal microbiomes during healthy and stressful periods. Host biochemical components and microbial changes were assessed per patient.  

A total of 106 participants (55 women, 51 men ranging from 25 to 75 years old) were followed for four years for early findings. Samples were taken from the participants quarterly and during self-reported stressful events. Environmental or medical stress events included respiratory viral infection, immunizations, weight gain, antibiotic treatment, colonoscopy, travel, and other self-reported stressors.  All participants had a median of seven visits, with a median of 1.6 years per participant. During each visit, blood samples were taken from the host molecular ‘omics, and stool and nasal swabs were taken for microbial purposes. HbA1C and fasting blood glucose was also taken at each visit. During the entry of the study, 51 participants had prediabetes, and 9 participants had diabetes. Out of the 66 participants that performed the insulin suppression test, 35 participants were insulin-resistant, and 31 participants were insulin-sensitive.  

The results found the molecules measured in the participants by laboratory tests and various microbiomes were relatively stable amongst each participant. Naturally, disease or infection occurrence precipitated high personal molecules. The integrated multi-omics discovered defense mechanism activation with innate immunity and adaptive responses during respiratory viral infections. One of the activation pathways was metabolic, which is associated with insulin receptor signaling. As expected, the insulin-resistant and insulin-sensitive groups varied at baseline and stress responses. Higher triglycerides and increased levels of immune molecules were noted in insulin-resistant participants. The impaired and delayed response to respiratory viral infections seen in insulin-resistant participants leads to chronic inflammation and developing type 2 diabetes. Moreover, insulin-resistance status is affected by the variations of the host-microbiome. Only IL-1RA and HSCRP, indicators of type 2 diabetes development, showed an increase of progression towards type 2 diabetes.  

Overall, researchers concluded that patients with prediabetes or insulin signaling intolerance experienced impaired and delayed responses to respiratory viral infections, leading to inflammation, which can intensify the development of diabetes. Logically, excluding the healthy patients, the nasal and gut microbiomes were affected in response to an infection or stressor. These multi-omics measurements helped examine the early detection of diabetes development individually.  

Practice Pearls: 

• This study identified human host and microbial changes that occurred during stressors such as respiratory viral infections, immunizations, and immunization triggers in prediabetes or insulin signaling intolerance.  
• Host-microbe interactions differ between insulin-resistant and insulin-sensitive participants. 
• Molecular indicators of type 2 diabetes, IL-1RA, and HSCRP were shown to have led to the onset of type 2 diabetes.  

“Three Studies Track People’s Microbiomes Through Health and Disease.” The Scientist Magazine®, www.the-scientist.com/news-opinion/three-studies-track-peoples-microbiomes-through-health-and-disease-65946. 

Zhou, Wenyu, et al. “Longitudinal Multi-Omics of Host–Microbe Dynamics in Prediabetes.” Nature News, Nature Publishing Group, May 29 2019, www.nature.com/articles/s41586-019-1236-x#Sec10. 

Maya Rudolph, Florida A&M University, College of Pharmacy & Pharmaceutical Sciences, PharmD Candidate 

See more about the role of the microbiome in prediabetes and type 2.