Microbial Biomarkers in the Diagnosis of Diabetes: Current Approaches and Future Directions

Abstract

Diabetes mellitus (DM) is a growing health concern across the globe, with its prevalence increasing by 1.6 to 3 times over the past three decades¹. It ranks among the top 10 deadliest non-communicable diseases worldwide, leading to premature deaths and disability ². Early diagnosis and prompt treatment are the only way to prevent disability and death. The human gut is colonized with different variety of bacteria, fungi, viruses, and eubacteria that play a vital role in digestion, immunity, and gut integrity. Gut dysbiosis refers to the alteration in the normal microbial composition of the gut. It has been found that dysbiosis is linked with metabolic syndrome and DM, supported by altered microbial abundance, shift in overall microbial composition, variety, and an increase F/B (Firmicutes/Bacteroidetes) ratio. This gut dysbiosis induces metabolic inflammation and disturbs glucose metabolism, contributing to the pathogenesis of DM. Some species are increased in DM, like Escherichia-Shigella, while beneficial species like Faecalibacterium prausnitzii are found to be decreased³.

Microbial biomarker refers to particular microbial species, genes, or metabolites linked to DM. Multiple techniques like 16S rRNA sequencing, metagenomics, and metabolomics could identify such microbial biomarkers, thereby aiding in the early diagnosis of DM, especially in high-risk individuals, like pregnant individuals. For example, increased Eisenbergiella, Tyzzerella 4, and Lachnospiraceae NK4A136, along with decreased Parabacteroides, Parasutterella, and Ruminococcaceae UCG 002 linked to fasting blood glucose level, highlighting their biomarker potential for early gestational diabetes mellitus (GDM). GDM affects a significant number of women during pregnancy. If predicted in the early stages of pregnancy and effective measures are implemented, complications and long-term maternal and fetal health risks could be reduced⁴_.

The applicability of microbiome-based diagnostics is challenging across diverse populations, as gut microbiota varies among individuals of different ethnicities due to factors like genetics, lifestyle, diet, medications, etc⁵_. Most data are primarily focused on Western populations, making the standardization of microbial biomarkers more difficult. Therefore, inclusive large-scale studies are needed to ensure reliability across diverse populations. Another hurdle in the implementation of microbial biomarkers as a diagnostic modality is the availability of methods like 16S rRNA and metagenomic sequencing, which are not feasible for primary care due to their high cost, complexity, and lengthy analysis times. For routine use, we need more techniques that are affordable, simpler, and provide quick results.

In conclusion, microbial biomarkers hold potential for the early diagnosis of DM, but further studies are needed for validation and advancements in techniques to enable their adoption in clinical practice.