A recent article in Medical News Today reported on the connection among obstructive sleep apnea (OSA), systemic hypertension (SH), and the gut microbiome.1 OSA and SH are known to be common and interrelated diseases.2 SH (or high blood pressure) is a very common chronic disease that frequently coexists with sleep-disordered breathing (such as OSA).2 It is estimated that at least 50% of adult patients with OSA have underlying SH.3
OSA and SH
OSA affects an estimated 22% of men and 17% of women.1 If undetected, it can increase the risk of developing heart disease.1 That’s why screening for the disease is so important. Testing for sleep apnea is done either by an overnight, in-laboratory study using polysomnography, or by using a convenient home sleep apnea test, or HSAT (the latter becoming more popular during the current pandemic).
Hypertension is even more common than OSA, affecting nearly half of adults in the United States.1 According to the Mayo Clinic, high blood pressure often has no symptoms. If untreated, it can cause health conditions over time such as heart disease—similar to the effects sleep apnea may have (which is why it is similarly important to screen and test for hypertension).4
Treatment for hypertension is readily available, but the medications do not work effectively for some patients.1 Why is that the case? The answer is not always clear, but researchers estimate that 75% of treatment-resistant hypertension cases have underlying OSA.2
So, researchers are studying links between OSA and SH, and some believe the gut microbiome may be the answer.1 Exploration of the gut microbiome is a new advance in medicine that has been linked to many comorbid illnesses, including SH and OSA.2
What is the gut microbiome and gut dysbiosis?
The gut microbiome is defined as “the collection of microorganisms including bacteria, archaea, viruses, and fungi found within the gut and their overall genetic information.”5 Simply put, our bodies (and, especially, our gastrointestinal tracts) are teeming with trillions of microorganisms. Mostly known for helping us digest food, scientists now look to microorganisms for associations between them and a range of medical conditions. Gut dysbiosis is “an imbalance or reduction in microbial diversity.”1
How could gut bacteria influence sleep apnea-related hypertension?
The Medical News Today article cited a study in the Journal of Clinical Sleep Medicine that offers a theory on how disordered breathing during sleep may influence bacterial populations: “Sleep apnea causes intermittent hypoxia or low levels of oxygen in the blood throughout the night. This hypoxia produces periodic decreases in the partial oxygen pressure gradient inside the tubes of the gastrointestinal system.
Consequently, bacteria that can only grow in low oxygen environments—obligate anaerobes—and those that can thrive with or without oxygen—facultative anaerobes—get a boost. As with any finely balanced ecosystem, when certain populations receive a leg up, they might push others aside.”2
Warring bacteria?
The 5 most common bacterial phyla that reside in the colon are Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Verrucomicrobia.6 Bacteroidetes (gram-negative) and Firmicutes (gram-positive) form more than 90% of gut microbiota.7 The hallmark of gut dysbiosis is an increase in the phylum Firmicutes compared with Bacteroidetes.1
Some people refer to Bacteroidetes as “good bacteria” because they produce short-chain fatty acids (SCFAs). Conversely, some think of Firmicutes as “bad” because they have a negative influence on glucose and fat metabolism.1
Epithelium damage
In animal studies, researchers have shown that a shift in bacterial populations can cause the degradation of mucins in the gut.8 Mucins help keep the gut lining (or epithelium) healthy. If the mucins suffer damage, the epithelium can become more permeable or “leaky,” as the damage disrupts junctions between epithelial cells.1 Also, good bacteria, which produce SCFAs from dietary fiber, are in shorter supply. SCFAs are a source of nutrition and energy9 for the epithelium. With the limited production of SCFAs, the epithelium takes a second hit. Again, this can cause dysfunction in the epithelium. In addition to the mucin degradation and drop in SCFAs, intermittent hypoxia itself can physically damage the epithelium. 1
This is how disordered breathing at night can cause damage to the intestinal epithelium through mucin breakdown, reduced levels of SCFAs, and physical damage through hypoxia.
Gut problems, hypertension, OSA
A damaged intestinal epithelium, or “leaky gut,”10 allows increased traffic from the gut into the blood. Compounds that the gut would normally trap and excrete from the body can now enter the blood and travel to distant organs and systems.1
Another effect of dysbiosis is an increase in bacterial species that produce toxins. A healthy epithelium might block these toxins, but an overly permeable epithelium allows these compounds to slip into the blood.1
Once they are in circulation, the body mounts a low-grade inflammatory response.11 Here, finally, is the intersection of OSA, gut bacteria, and hypertension.To summarize, intermittent hypoxia experienced during the night disturbs the microbiome. This bacterial disturbance makes the gut epithelium “leaky” and allows toxins to reach into the blood. This sparks inflammation and, therefore, increases the risk of hypertension and other cardiovascular problems. 1
As we move toward a more personalized approach to OSA management, it will be critical to examine the effect of positive airway pressure (PAP) therapy on gut dysbiosis and the changes in blood pressure in patients with OSA.2
References
1.
Newman T. Hypertension, gut bacteria, and sleep apnea: is there a link? Medical News Today. October 16, 2021. Accessed November 1, 2021. https://www.medicalnewstoday.com/articles/hypertension-gut-bacteria-and-sleep-apnea-is-there-a-link
2.
Mashaqi S, Gozal D. Obstructive sleep apnea and systemic hypertension: gut dysbiosis as the mediator? J Clin Sleep Med. 2019;15(10):1517-1527. doi: 10.5664/jcsm.7990
3.
Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;342(19):1378-1384. doi: 10.1056/NEJM200005113421901
4.
Mayo Clinic staff. High blood pressure (hypertension). Mayo Clinic Patient Care and Health Information. July 21, 2021. https://www.mayoclinic.org/diseases-conditions/high-blood-pressure/symptoms-causes/syc-20373410
5.
Neuman H, Koren O. The Gut Microbiome. Encyclopedia of cell biology. Vol 2, 2016, pp 799-808. Aug 20, 2015.
6.
Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 2010;464(7285)59-65. doi: 10.1038/nature08821
7.
James L, Gorwitz RJ, Jones RC, et al. Methicillin-resistant Staphylococcus aureus infections among healthy full-term newborns. Arch Dis Child Fetal Neonatal Ed. 2008;931:F40-F44.
8.
Moreno-Indias I, Torres M, Montserrat JM, et al. Intermittent hypoxia alters gut microbiota diversity in mouse model of sleep apnoea.
Eur Respir J. 2015;45(4):1055-1065. doi: 10.1183/09031936.00184314
9.
Vinolo MAR, Rodrigues HG, Nachbar RT, Curi R. Regulation of inflammation by short chain fatty acids. Nutrients. 2011;3(10):858-876. doi: 10.3390/nu3100858
10.
Eske J. What to know about leaky gut syndrome. Medical News Today. August 21, 2019. Accessed November 1, 2021. https://www.medicalnewstoday.com/articles/326117
11.
Felman A. Everything you need to know about inflammation. Medical News Today. Updated April 13, 2020. Accessed November 1, 2021. https://www.medicalnewstoday.com/articles/248423