Gut microbiota analyses of Saudi populations for type 2 diabetes-related phenotypes reveals significant association

Abstract

Background Large-scale gut microbiome sequencing has revealed key links between microbiome dysfunction and metabolic diseases such as type 2 diabetes (T2D). To date, these efforts have largely focused on Western populations, with few studies assessing T2D microbiota associations in Middle Eastern communities where T2D prevalence is now over 20%. We analyzed the composition of stool 16S rRNA from 461 T2D and 119 non-T2D participants from the Eastern Province of Saudi Arabia. We quantified the abundance of microbial communities to examine any significant differences between subpopulations of samples based on diabetes status and glucose level. Results In this study we performed the largest microbiome study ever conducted in Saudi Arabia, as well as the first-ever characterization of gut microbiota T2D versus non-T2D in this population. We observed overall positive enrichment within diabetics compared to healthy individuals and amongst diabetic participants; those with high glucose levels exhibited slightly more positive enrichment compared to those at lower risk of fasting hyperglycemia. In particular, the genus Firmicutes was upregulated in diabetic individuals compared to non-diabetic individuals, and T2D was associated with an elevated Firmicutes/Bacteroidetes ratio, consistent with previous findings. Conclusion Based on diabetes status and glucose levels of Saudi participants, relatively stable differences in stool composition were perceived by differential abundance and alpha diversity measures. However, community level differences are evident in the Saudi population between T2D and non-T2D individuals, and diversity patterns appear to vary from well-characterized microbiota from Western cohorts. Comparing overlapping and varying patterns in gut microbiota with other studies is critical to assessing novel treatment options in light of a rapidly growing T2D health epidemic in the region. As a rapidly emerging chronic condition in Saudi Arabia and the Middle East, T2D burdens have grown more quickly and affect larger proportions of the population than any other global region, making a regional reference T2D-microbiome dataset critical to understanding the nuances of disease development on a global scale.

Metagenomic Shotgun Sequencing Reveals Specific Human Gut Microbiota Associated with Insulin Resistance and Body Fat Distribution in Saudi Women

“…However, α-diversity trended higher in the high HOMA-IR group. The previous study conducted in Saudi Arabia of individuals with and without T2DM also found a trend towards increased diversity among participants with T2DM and higher glucose levels [ 51 ], a finding similar to other work from the Middle East [ 64 ] but different from results from Western populations. For instance, a population-based study that used two European cohorts found that lower gut microbiota diversity was associated with higher levels of HOMA-IR irrespective of BMI [ 65 ].…”

“…Although this work investigated markers of diabetes rather than diabetes itself, the relationships found supporting studies showing that gut microflora differs between individuals with and without T2DM [ 50 ]. One study looked at this relationship specifically among patients in Saudi Arabia and found that Firmicutes levels were upregulated, and the Firmicutes/Bacteroidetes ratio was elevated among those with T2DM compared to those without [ 51 ]. Further, the study revealed that both men and women with T2DM had a higher abundance of prevotellaceae compared to those without [ 51 ], in contrast to earlier findings demonstrating that gut microbiota composition varies between genders [ 52 , 53 ].…”

“…One study looked at this relationship specifically among patients in Saudi Arabia and found that Firmicutes levels were upregulated, and the Firmicutes/Bacteroidetes ratio was elevated among those with T2DM compared to those without [ 51 ]. Further, the study revealed that both men and women with T2DM had a higher abundance of prevotellaceae compared to those without [ 51 ], in contrast to earlier findings demonstrating that gut microbiota composition varies between genders [ 52 , 53 ]. In comparison to other populations, studies conducted on Chinese and Egyptian populations showed that the composition of gut microbiota is, in fact, associated with T2DM [ 54 , 55 ].…”

Association of the gut microbiota with clinical variables in obese and lean Emirati subjects

“…In contrast, genera that were higher in obese subjects positively correlated with BMI and FM ( Acidaminococcus ) as well as WHtR ( Lachnospira ), suggesting them as potential microbiota biomarkers of obesity ( Companys et al, 2021 ). In addition, levels of Acidamonicoccus positively correlated with type 2 diabetes in the Saudi population ( Al-Muhanna et al, 2022 ). Contrary to our results, a study in overweight adults showed that reduced Lachnospira abundance was associated with weight gain ( Companys et al, 2021 ).…”

Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease

“…The etiology and pathogenesis of insulin resistance and T2DM have been closely linked to the human microbiome [24][25][26][27] . Patients with impaired insulin and glucose homeostasis exhibit microbiome composition alterations in the gut 21,23,[25][26][27][28][29] , skin [30][31][32][33] , and other body sites [34][35][36][37][38][39][40] , reflecting an ecological dysbiosis characterized by altered microbial alpha diversity 25,41 , decreased compositional stability 42,43 , and greater inter-individual variability 25 . Compromised integrity of mucosal and skin barriers, often associated with insulin resistance, may potentiate microbial translocation, thereby exacerbating systemic inflammation [44][45][46][47] .…”