Abstract Large-scale gut microbiome sequencing has revealed key links between microbiome dysfunction and metabolic diseases such as 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-T2Dparticipants 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. 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 participants compared to non-diabetic participants, and T2D was associated with an elevated Firmicutes/Bacteroidetes ratio, consistent with previous findings. 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. Author summary The rates of Type 2 diabetes (T2D) in Saudi Arabia have risen dramatically in the last several decades due to socio-economic changes resulting in changes in dietary and sedentary lifestyles. This emergence has grown more rapidly and affects larger proportions of the population with estimates of T2D prevalence impacting 25% of the population. There is a paucity of microbiome data from Middle Eastern populations, and previous studies have been conducted on small sample sizes. Here we report on the first-ever characterization of gut microbiota T2D versus non-T2D and largest microbiome study ever conducted in a Middle Eastern country. The datasets from this study are important to create a regional reference T2D-microbiome catalogue which will propel the understanding of regional gut flora which are associated with T2D development. Based on T2D status and quantified glucose levels of Middle Eastern participants, relatively stable differences in stool composition were observed by differential abundance and alpha diversity measures. 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.

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