OSA is a comprehensive systemic disease associated with cardiovascular disease and metabolic abnormalities. IH plays an important role in OSA and its associated multisystem pathologies, but its mechanism of action is not fully understood. This study demonstrated that gut microbiota alterations are associated with his OSA patient’s intestinal barrier his biomarkers and that the dominant genera of her severe OSA are glucose, lipids, neutrophils, monocytes, and his BMI. Network analysis identified associations between gut microbiota, gut barrier biomarkers, and AHI. These alterations may play a pathophysiologic role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to the multisystem morbidity of OSA.
In this study, we found an association between OSA and an increase in intestinal barrier biomarkers. This is also associated with a unique microbiome profile, with D-LA levels being positively correlated with Lachnoclostridium, Megamonas, and Fusobacterium and negatively correlated with Peptoclostridium and Anaeros types. I-FABP levels were negatively correlated with Peptoclostridium. β-diversity showed significant differences in microbial community composition between high and low D-LA groups, with high plasma D-LA positively associated with Ruminococcus_2, Lachnoclostridium, and Lachnospiraceae_UCG_006. Although there was a negative correlation with Senegalese trout Syria, I-FABP-rich fecal microbiota were enriched in Alloprevotella. It suggests that Increased intestinal barrier alterations in OSA are well documented, including increased circulating I-FABP, D-LA, and lipopolysaccharide-binding protein.23,30,31We previously reported that circulating D-LA and I-FABP were significantly elevated in OSA compared to healthy subjects.19.
Based on current research and reports in the relevant literature, repeated hypoxia may be a cause of epithelial damage that may lead to abnormalities in intestinal flora, and these detrimental factors contribute to intestinal permeability. We speculate that it may impair bowel function by increasing Repeated hypoxia causes epithelial damage that can lead to intestinal dysbiosis.Repeated hypoxia and reoxygenation can impair gut function by increasing intestinal permeability, bacterial translocation and reducing tight junction integrity.25,26Increased intestinal barrier alterations in OSA, such as increased circulating I-FABP, D-LA, and lipopolysaccharide-binding protein, are well described.18,27,28A mouse model of sleep apnea showed that intestinal colonization with Prevotella and desulfovibrio contributes to increased intestinal permeability29In humans, D-lactic acid-producing bacteria such as streptococci and enterococci have been found on the faces of patients with chronic fatigue syndrome.12Furthermore, significant increases in gut bacterial translocation products (endotoxin and D-lactic acid) were associated with systemic inflammation and could predict adverse cardiovascular events.30We previously reported that circulating D-LA and I-FABP were significantly elevated in OSA compared to healthy subjects.14The study also revealed a relationship between OSA and increased intestinal barrier biomarkers. These biomarkers were also associated with his profile in a unique microbiome. D-LA levels were positively correlated with Lachnoclostridium, Megamonas, and Fusobacterium, and negatively with Peptoclostridium and Anaeros types. Levels of I-FABP were negatively correlated with Peptoclostridia. β-diversity showed significant differences in microbial community composition between the high and low D-LA groups. High plasma D-LA was positively correlated with Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006 and negatively with Senegalese Syrian, whereas fecal microbiota with high I-FABP was associated with Alloprevothera was concentrated in A damaged epithelial barrier was shown to be associated with the enrichment of specific microbiota. Both Fusobacterium and Lachnoclostridium are different bacteria and were confirmed again by both DESeq and LEFse methods.
Furthermore, hypoxia directly affects the gut microbiota. Morenos-Indias et al. An OSA-mimicking animal model showed profound changes in gut microbial community structure32IH exposed in a mouse model cumulatively disrupted the fecal microbiome and metabolism33These animal models resembled models of chronic OSA and showed altered gut microbiota compared to normal oxygen levels. In humans, elevated intestinal oxygen levels also affect the composition of the fecal and mucoadhesive microbiota (eg, Proteobacteria and Actinobacteria).30Repeated hypoxia due to upper airway obstruction can cause focal symptoms in all blood-perfused organs34Therefore, microbiome changes can occur in different mucous membranes in OSA. For example, changes in the nasal microbiome are associated with OSA and inflammatory biomarkers.35Lung microbiota in OSA differs from that in control subjects36The oral microbiota is significantly disturbed in pediatric patients with OSA, leading to OSA-related metabolomics37Two key features of OSA, IH and SF, also established a hypoxic environment in many parts of the gastrointestinal tract.38Alvenberg et al.We observed that host oxygenation affects intestinal lumen oxygenation and alters gut microbial composition30Decreased oxygen in the gut allows obligate anaerobes (such as proteobacteria and actinobacteria) to become more competitive and overgrowth.30At the same time, increased tissue oxygenation can have direct effects on microbes, such as decreased anaerobes.39The gut may therefore provide a unique environment conducive to living aerobic and facultative anaerobes.
In our study, OSA was associated with changes in β-diversity in the fecal microbiome. Among his OSA patients of varying severity, the intestinal flora of Fusobacterium and Lachnoclostridium were abundant, while Ruminococcaceae_UCG_013 was reduced compared to his OSA-free. Fusobacterium, Megamonas, and Lachnospiraceae_UCG_006 were abundant, while Ruminococcaceae_UCG_013 was reduced in severe OSA. This is consistent with Ko C. et al., where the relative abundance of Ruminococcaceae was greater in the control group.11The relative abundance of Megamonas was opposite to Ko C. et al. This may be due to different DNA extraction kits, different PCR amplification primers and clustering methods, or different living regions and lifestyles of the participants, or relatively small samples. However, not only was there an enrichment of Megamonas in the severe group, but an increase was also seen in the moderate group. In contrast, Ko C. et al. A reduction in megamonas was seen only in the severe group. Future clinical studies are needed to validate our results. Next, Fusobacterium and Peptoclostridium showed independent relationships with severe OSA. This may help identify subjects at risk for gut microbiota disorders associated with OSA. Some of the fecal microbiome differences described above, such as Lachnoclostridium and Lachnospiraceae_UCG_006, were also associated with intestinal barrier biomarkers. Moreover, the differences in the microbiota characteristics of the moderate group were very close to those of the severe group. The validity of comparing the group with the non-OSA group was supported.40.
Moreover, microbiota features in severe OSA were not only significantly correlated with sleep parameters, but also associated with lipids and BMI. Anaerobicity was correlated with fasting blood glucose, and peptoclostridium was associated with neutrophils and monocytes.Therefore, these microbiota alterations can lead to low-grade chronic inflammation41, immune and metabolic disorders.Fusobacteria are associated with cardiovascular disease42colorectal cancer43oral and pulmonary infections44,45Megamonas are correlated with chronic kidney disease46Alloprevotella is linked to infections and diabetes47,48These microbial alterations may therefore play an important role in multisystem and multiorgan disease caused by OSA. In our study, we also found that microbiota features of the severe OSA group were significantly correlated with intestinal barrier biomarkers. Co-occurrence network analysis identified associations between the fecal microbiome, gut barrier biomarkers and AHI. These results suggest that intestinal barrier dysfunction is associated with bacterial dysfunction in OSA.
Recently, Mashaqi S, in his review of OSA and gut microbiota, found that most studies were performed in animal models with increased F/B ratios.41Also, among children, snorers had a higher F/B ratio than controls.26Unlike previous animal models and studies in children, no significant differences in alpha diversity or F/B ratios were found among OSA patients. However, our results are consistent with another adult OSA study.11This is likely due to the different intestinal populations of humans and animals. Corrado et al. We enrolled the snoring child in the questionnaire and did not perform the PSG test, so without this test we could not diagnose the child’s snoring or her OSA.Additionally, the child’s intestines may not be fully developed.49and their dietary structure and tolerance to hypoxia may differ from those of adults. Further studies on the gut microbiota of adult OSA are needed in the future to support our findings.
Advantages of this study include not only the clinical assessment of the relationship between the gut microbiome and OSA, but also the novel assessment of the association with blood levels of D-LA and I-FABP. We supported the pathophysiological role of intestinal flora and alterations of the intestinal barrier in OSA. However, it has some drawbacks. The first drawback is the relatively small sample size involved. Intestinal flora with OSA was statistically significantly different from without OSA, whereas no differences in α and β diversity were observed with mild and moderate OSA.Second, we did not collect detailed dietary habits of the participants and physical activity that may affect the gut microbiome.50,51Third, we focused on the most important sleep parameters, but did not include other sleep metrics such as sleep stages and sleep efficiency. These need to be considered in the future. In addition, we did not assess the impact of microbiota-modifying strategies (CPAP, microbial ecological modulators, etc.) on gut barrier biomarkers and gut microbiota. Future studies may require more longitudinal and interventional investigations to assess causality. The critical role of precision medicine in developing personalized disease treatment protocols. Gut microbial composition and metabolic component approaches will also be an important part of the individualized treatment of OSA. The present study provides a scientific basis for the involvement of intestinal flora in OSA and pathogenesis, and how OSA regulates host metabolism via intestinal flora deserves further study and domestic There are few reports of relevant clinical studies outside. For this reason, further studies in multicenter and large-sample clinical trials are needed in the future.