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Abstract The microbial communities of the oral cavity are important elements of oral and systemic health. With emerging evidence highlighting the heritability of oral bacterial microbiota, this study aimed to identify host genome variants that influence oral microbial traits. Using data from 16S rRNA gene amplicon sequencing, we performed genome-wide association studies with univariate and multivariate traits of the salivary microbiota from 610 unrelated adults from the Danish ADDITION-PRO cohort. We identified six single nucleotide polymorphisms (SNPs) in human genomes that showed associations with abundance of bacterial taxa at different taxonomical tiers (P

Background: Schizophrenia (SCZ) is a heterogeneous neuropsychiatric disorder for which current treatment has insufficient efficacy and severe adverse effects. The modifiable gut microbiome might be a potential target for intervention to improve neurobiological functions through the gut-microbiome-brain axis. Methods: In this case-control study, gut microbiota of 132 patients with SCZ and increased waist circumference were compared with gut microbiota of two age- and sex-matched control groups, composed of 132 healthy individuals and 132 individuals with metabolic syndrome. Shotgun sequencing was used to characterize fecal samples at the taxonomic and functional levels. Cognition of the patients with SCZ was evaluated using the Brief Assessment of Cognition instrument. Results: SCZ gut microbiota differed significantly from those of healthy control subjects and individuals with metabolic syndrome in terms of richness and global composition. SCZ gut microbiota were notably enriched in Flavonifractor plautii, Collinsella aerofaciens, Bilophila wadsworthia, and Sellimonas intestinalis, while depleted in Faecalibacterium prausnitzii, Ruminococcus lactaris, Ruminococcus bicirculans, and Veillonella rogosae. Functional potential of the gut microbiota accounted for 11% of cognition variability. In particular, the bacterial functional module for synthesizing tyrosine, a precursor for dopamine, was in SCZ cases positively associated with cognitive score (ρ = 0.34, q ≤ .1). Conclusions: Overall, this study shows that the gut microbiome of patients with SCZ differs greatly from that of healthy control subjects or individuals with metabolic syndrome. Cognitive function of patients with SCZ is associated with the potential for gut bacterial biosynthesis of tyrosine, a precursor for dopamine, suggesting that gut microbiota might be an intervention target for alleviation of cognitive dysfunction in SCZ.

Abstract Background Type 2 diabetes (T2D), a multifactorial disease influenced by host genetics and environmental factors, is the most common endocrine disease. Several studies have shown that the gut microbiota as a close-up environmental mediator influences host physiology including metabolism. The aim of the present study is to examine the compositional and functional potential of the gut microbiota across individuals from Denmark and South India with a focus on T2D. Many earlier studies have investigated the microbiome aspects of T2D, and it has also been anticipated that such microbial associations would be dependent on diet and ethnic origin. However, there has been no large scale trans-ethnic microbiome study earlier in this direction aimed at evaluating any “universal” microbiome signature of T2D. Methods 16S ribosomal RNA gene amplicon sequencing was performed on stool samples from 279 Danish and 294 Indian study participants. Any differences between the gut microbiota of both populations were explored using diversity measures and negative binomial Wald tests. Study samples were stratified to discover global and country-specific microbial signatures for T2D and treatment with the anti-hyperglycemic drug, metformin. To identify taxonomical and functional signatures of the gut microbiota for T2D and metformin treatment, we used alpha and beta diversity measures and differential abundances analysis, comparing metformin-naive T2D patients, metformin-treated T2D patients, and normoglycemic individuals. Results Overall, the gut microbial communities of Danes and Indians are compositionally very different. By analyzing the combined study materials, we identify microbial taxonomic and functional signatures for T2D and metformin treatment. T2D patients have an increased relative abundance of two operational taxonomic units (OTUs) from the Lachnospiraceae family, and a decreased abundance of Subdoligranulum and Butyricicoccus. Studying each population per se, we identified T2D-related microbial changes at the taxonomic level within the Danish population only. Alpha diversity indices show that there is no significant difference between normoglycemic individuals and metformin-naive T2D patients, whereas microbial richness is significantly decreased in metformin-treated T2D patients compared to metformin-naive T2D patients and normoglycemic individuals. Enrichment of two OTUs from Bacteroides and depletion of Faecalibacterium constitute a trans-ethnic signature of metformin treatment. Conclusions We demonstrate major compositional differences of the gut microbiota between Danish and South Indian individuals, some of which may relate to differences in ethnicity, lifestyle, and demography. By comparing metformin-naive T2D patients and normoglycemic individuals, we identify T2D-related microbiota changes in the Danish and Indian study samples. In the present trans-ethnic study, we confirm that metformin changes the taxonomic profile and functional potential of the gut microbiota.

Abstract Background Recent studies have indicated an association of gut microbiota and microbial metabolites with type 2 diabetes mellitus (T2D). However, large-scale investigation of the gut microbiota of “prediabetic” (PD) subjects has not been reported. Identifying robust gut microbiome signatures of prediabetes and characterizing early prediabetic stages is important for the understanding of disease development and could be crucial in early diagnosis and prevention. Methods The current study performed amplification and sequencing on the variable regions (V1–V5) of the 16S rRNA genes to profile and compare gut microbiota of prediabetic individuals (N = 262) with normoglycemic individuals (N = 275) from two cohorts in India and Denmark. Similarly, fasting serum inflammatory biomarkers were profiled from the study participants. Results After correcting for strong country-specific cohort effect, 16 operational taxonomic units (OTUs) including members from the genera Prevotella9, Phascolarctobacterium, Barnesiella, Flavonifractor, Tyzzerella_4, Bacteroides, Faecalibacterium, and Agathobacter were identified as enriched in normoglycaemic subjects with respect to the subjects with prediabetes using a negative binomial Wald test. We also identified 144 OTUs enriched in the prediabetic subjects, which included members from the genera Megasphaera, Streptococcus, Prevotella9, Alistipes, Mitsuokella, Escherichia/Shigella, Prevotella2, Vibrio, Lactobacillus, Alloprevotella, Rhodococcus, and Klebsiella. Comparative analyses of relative abundance of bacterial taxa revealed that the Streptococcus, Escherichia/Shigella, Prevotella2, Vibrio, and Alloprevotella OTUs exhibited more than fourfold enrichment in the gut microbiota of prediabetic subjects. When considering subjects from the two geographies separately, we were able to identify additional gut microbiome signatures of prediabetes. The study reports a probable association of Megasphaera OTU(s) with impaired glucose tolerance, which is significantly pronounced in Indian subjects. While the overall results confirm a state of proinflammation as early as in prediabetes, the Indian cohort exhibited a characteristic pattern of abundance of inflammatory markers indicating low-grade intestinal inflammation at an overall population level, irrespective of glycemic status. Conclusions The results present trans-ethnic gut microbiome and inflammation signatures associated with prediabetes, in Indian and Danish populations. The identified associations may be explored further as potential early indicators for individuals at risk of dysglycemia.

Background: Offspring of mothers with gestational diabetes mellitus (GDM) have increased risk of developing metabolic disorders as they grow up. Microbial colonization of the newborn gut and environmental exposures affecting the configuration of the gut microbiota during infancy have been linked to increased risk of developing disease during childhood and adulthood. In a convenience sample, we examined whether the intestinal tract of children born to mothers with GDM is differentially colonized in early life compared to offspring of mothers with normal gestational glucose regulation. Secondly, we examined whether any such difference persists during infancy, thus potentially conferring increased risk of developing metabolic disease later in life.Methods: Fecal samples were collected from children of mothers with (n = 43) and without GDM (n = 82) during the first week of life and again at an average age of 9 months. The gut microbiota was characterized by 16S rRNA gene amplicon sequencing (V1–V2). Differences in diversity and composition according to maternal GDM status were assessed, addressing potential confounding by mode of delivery, perinatal antibiotics treatment, feeding and infant sex.Results: Children of mothers with GDM were featured by a differential composition of the gut microbiota, both during the first week of life and at 9 months, at higher taxonomic and OTU levels. Sixteen and 15 OTUs were differentially abundant after correction for multiple testing during the first week of life and at 9 months, respectively. Two OTUs remained differentially abundant after adjustment for potential confounders both during the first week of life and at 9 months. Richness (OTU) was decreased in neonates born to mothers with GDM; however, at 9 months no difference in richness was observed. There was no difference in Shannon's diversity or Pielou's evenness at any timepoint. Longitudinally, we detected differential changes in the gut microbiota composition from birth to infancy according to GDM status.Conclusion: Differences in glycaemic regulation in late pregnancy is linked with relatively modest variation in the gut microbiota composition of the offspring during the first week of life and 9 months after birth.

Abstract Background Imbalances of gut microbiota composition are linked to a range of metabolic perturbations. In the present study, we examined the gut microbiota of women with gestational diabetes mellitus (GDM) and normoglycaemic pregnant women in late pregnancy and about 8 months postpartum. Methods Gut microbiota profiles of women with GDM (n = 50) and healthy (n = 157) pregnant women in the third trimester and 8 months postpartum were assessed by 16S rRNA gene amplicon sequencing of the V1-V2 region. Insulin and glucose homeostasis were evaluated by a 75 g 2-h oral glucose tolerance test during and after pregnancy. Results Gut microbiota of women with GDM was aberrant at multiple levels, including phylum and genus levels, compared with normoglycaemic pregnant women. Actinobacteria at phylum level and Collinsella, Rothia and Desulfovibrio at genus level had a higher abundance in the GDM cohort. Difference in abundance of 17 species-level operational taxonomic units (OTUs) during pregnancy was associated with GDM. After adjustment for pre-pregnancy body mass index (BMI), 5 of the 17 OTUs showed differential abundance in the GDM cohort compared with the normoglycaemic pregnant women with enrichment of species annotated to Faecalibacterium and Anaerotruncus and depletion of species annotated to Clostridium (sensu stricto) and to Veillonella. OTUs assigned to Akkermansia were associated with lower insulin sensitivity while Christensenella OTUs were associated with higher fasting plasma glucose concentration. OTU richness and Shannon index decreased from late pregnancy to postpartum regardless of metabolic status. About 8 months after delivery, the microbiota of women with previous GDM was still characterised by an aberrant composition. Thirteen OTUs were differentially abundant in women with previous GDM compared with women with previous normoglycaemic pregnancy. Conclusion GDM diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with normoglycaemic pregnant women, and 8 months after pregnancy, differences in the gut microbiota signatures are still detectable. The gut microbiota composition of women with GDM, both during and after pregnancy, resembles the aberrant microbiota composition reported in non-pregnant individuals with type 2 diabetes and associated intermediary metabolic traits.