Gut bacteria implicated in sleep apnea
Gut microbiota were suspected of being implicated in sleep apnea. A Mendelian randomization study 1 confirms its causal role, pointing at bacteria and bacterial metabolites.
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Obstructive sleep apnea, which can present in early childhood as well as in elderly subjects, is based on a complex etiology (tonsillar hypertrophy in children, reduction of pulmonary volume, obesity, etc.).
Gut microbiota has also been highlighted by several studies suggesting the existence of dysbioses, but its causal role is still unproven. That is exactly what a Chinese team set out to do using Mendelian randomization, which allowed them to set aside many confounding factors and biases and to show that the microbiota and its metabolites are the cause, and not the consequence, of sleep apnea.
The protective effect of the Ruminococcaceae family
In practice, the researchers conducted the study using pre-existing databases: for sleep apnea, the genetic data of the Finnish project FinnGen 2, which includes 33,423 patients with sleep apnea and 307,648 controls; for microbiota, the data of the MiBioGen 3 consortium, which has collected and analyzed the genotypes and data for fecal microbiota 16S from 18,340 people.
The Mendelian randomization focused on 196 gut microbial taxa, 83 types of microbial metabolites, and the risk of sleep apnea. It showed that some bacteria increased the risk of sleep apnea (the genus Ruminococcaceae UCG009 and the genus Subdoligranulum) while others (the Ruminococcaceae family, the genus Coprococcus2, the genus Eggerthella, and the genus Eubacterium) decreased it.
The protective effect of the Ruminococcaceae bacterial family could be due to the ability of these bacteria to produce (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) , which reduce inflammation, reinforce the intestinal barrier, and limit the proliferation of pathogenic bacteria, but also due to their implication in the metabolism of bile acids, known for their role in sleep and regulating sleep cycles.
Microbial metabolites incriminated
The study also highlights the role of other microbial metabolites: leucine and 3-dehydrocarnitine are associated with an increased risk of sleep apnea, while gamma-glutamylvaline and betaine show protective effects. Some of these molecules have already been incriminated in previous studies: elevated leucine levels were observed in children with sleep apnea; on the other hand, among patients who had been prescribed a mask to treat sleep apnea, leucine levels fell rapidly.
Therefore, disturbances to our gut microbiota and alterations in the metabolites produced by the bacteria of our digestive tract seem to have beneficial or harmful consequences for sleep apnea based on their profile. This causal relationship could be due to a systemic pro-inflammatory response.
These results pave the way for further work: studies on non-Finnish populations; decryption of the interactions between microbiota and immunity, flora and inflammation, and the gut-brain axis; interventional study measuring the effects of diet, probiotics, or fecal transplants on patient symptoms.
