Obstructive sleep apnea is related to alterations in fecal microbiome and impaired intestinal barrier function

Abstract

Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. A prospective case-control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect fecal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers-intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Plasma D-LA and I-FABP were significantly elevated in patients with OSA. The severity of OSA was related to differences in the structure and composition of the fecal microbiome. Enriched Fusobacterium, Megamonas, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea-hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the fecal microbiome, intestinal barrier biomarkers, and AHI. The study confirms that changes in the intestinal microbiota are associated with intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA.

Figure 1

Patient flow chart.

Figure 2

Heatmap of 48 stool samples at the genus level. Stool samples demonstrate the high relative abundance of Bacteroides, Faecalibacterium, Blautia, Blautia, and Lachnospira(relative abundance ≥ 0.5% were annotated, < 0.5% were classified as others).

Figure 3

β diversity differences in different severity groups of OSA and severe OSA. PCOA (Unweigther-Unifrac distance) between (A) different severity groups of OSA versus no OSA (Adonis P = 0.044) and (B) severe OSA versus no OSA (adonis P = 0.005).

Figure 4

Taxa differences in different severity OSA. LEfSe identifies microbiota differences in (A) Different severity groups of OSA versus no OSA (Kruskal–Wallis), (B) severe OSA versus no OSA (Wilcox). (C) Mild OSA versus no OSA(Wilcox). (D) moderate OSA versus no OSA (Wilcox). (E) Scatter plot of the bacteria at the genus level with relative abundance greater than 0.5% in all samples in severe OSA participants (Wilcox).

Figure 5

Correlation between changes in intestinal microbiota and intestinal barrier dysfunction. Beta diversity between (A) high versus low D-LA (Adonis p = 0.049) and (B) high versus low I-FABP levels (Adonis p = ns). (C) The gut microbiota with high D-LA was enriched with Ruminococcus_2, Lachnoclostridium, and Lachnospiraceae_UCG_006 and decreased with Senegalimascilia (Wilcox). (D) The gut microbiota with high I-FABP was enriched with Alloprevotella (Wilcox).

Figure 6

Network between taxa, AHI, and intestinal barrier biomarkers. SparCC was used to construct a genus taxa network. Positively related variables were kept in the network (The correlation coefficient between bacteria and clinical indicators was ≥ 0.4, and between bacteria and bacteria was ≥ 0.7). AHI, D-.LA, and I-FABP were associated with unique taxa. Streptobacillus, Prevotellaceae_UCG_003, and Rikenellaceae_RC9_gut_group were the common genera. Gut commensals co-occurred AHI and intestinal barrier biomarkers (D-LA and I-FABP).