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Vol. 55. Issue 1.
Pages 7-8 (January 2019)
Vol. 55. Issue 1.
Pages 7-8 (January 2019)
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Sleep and the Microbiome: A Two-Way Relationship
Sueño y microbioma: una relación bidireccional
Nuria Farréa, David Gozalb,
Corresponding author

Corresponding author.
a Heart Failure Programme, Department of Cardiology, Hospital del Mar, Heart Diseases Biomedical Research Group, Hospital del Mar Medical Research Institute (IMIM), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
b Sections of Pediatric Sleep Medicine and Pediatric Pulmonology, Department of Pediatrics, Biological Sciences Division, The University of Chicago, Chicago, IL, United States
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The gut microbiome is a polymicrobial ecosystem that coexists with the human body and acts symbiotically with it. This system can be modified in different situations associated with both everyday life and various pathological situations. In recent decades, it has become clear that many respiratory illnesses affect the quantity and quality of sleep among patients. In addition to the obvious case of respiratory diseases during sleep, sleep is also adversely affected in patients with lung cancer1 and in those with chronic obstructive pulmonary disease2 and obesity-hypoventilation syndrome.3 The aim of this editorial is to analyze the existing evidence on the relationship between sleep disturbances (fragmentation and circadian rhythm) and the gut microbiome, and the consequences this can have in patients.

Restricted and Fragmented Sleep

Although revealing data are available, the relationship between sleep restriction and alteration of the gut microbiome is not entirely clear. While Benedict et al. showed that a short period (2 nights) of sleep restriction was associated with changes in the gut microbiome in 9 healthy adults,4 a study carried out in 11 healthy adults showed that periods of 5 days of sleep restriction (4h per night) followed by nights of recovery were not associated with changes in the richness, diversity or composition of the gut microbiome.5 However, better quality sleep, as assessed by the Pittsburgh Sleep Quality Index questionnaire, was associated with higher proportions of the phyla Verrucomicrobia and Lentisphaerae6 in healthy adults.

In contrast, sleep fragmentation (SF), a much more common situation in clinical settings, clearly contributes to the phenotypic consequences of obstructive sleep apnea syndrome plus inflammation and oxidative stress that lead to metabolic and vascular changes,7 even in the absence of sleep restriction. In fact, studies in mouse models showed that SF is associated with both significant changes in the structure of the gut microbiome, and metabolite alterations in feces.8 An increase in intestinal permeability was also observed when “fecal water” from animals submitted to SF, prepared from the soluble fraction of the gut microbiome, was applied to a monolayer of colonic cells. These same authors found that the administration of fecal pellets from mice subjected to SF to germ-free mice was associated with the development of the same systemic manifestations as SF animals, despite the fact that their sleep had not been disturbed.8 These metabolic changes seem to be mediated by changes in the receptors of fatty acids in the intestine. For example, treatment with a selective free fatty acid receptor 4 agonist reverses the increase in food intake and weight gain and decreases the inflammation in visceral white adipose tissue and insulin resistance associated with SF.9 Increased systemic levels of lipopolysaccharide-binding protein, a marker of low-grade endotoxemia, was also independently associated with body mass index, insulin resistance, and severity of obstructive sleep apnea syndrome in children.10 These studies show that the metabolic alterations associated with SF can be the result of simultaneous changes in the gut microbiome. However, there is much less evidence on how changes in the gut microbiome affect sleep. A study in mice treated with inactivated Lactobacillus brevis SBC8803 for 4 weeks showed shorter periods of non-REM phase during sleep, as well as longer periods of wakefulness during the second half of the night, and a tendency to increase the total amount of time spent in non-REM sleep during the day.11 In addition, a study by Thompson et al. showed that a diet rich in probiotics, lactoferrin, and milk fat globule membrane in a murine animal model increased the amount of Lactobacillus rhamnosus in feces and improved sleep quality, by facilitating non-REM sleep consolidation and enhancing REM sleep rebound, after stressor exposure.12

Alteration of the Circadian Rhythm

An altered circadian rhythm is associated with changes in the gut microbiome, particularly in the presence of another stressor. Both Voigt et al.13 and Bishehsari et al.14 showed in a murine model that combining a change in the light/dark cycle with a diet high in fat and sugar or alcohol was associated with alterations in the gut microbiome.

Thaiss et al. evaluated the diurnal oscillation of the composition of the gut microbiome15 by subjecting a group of mice to a light/dark cycle that shifted by 8h over a 3-day period, after which the animals returned to the original light/dark cycle. This cycle was repeated every 3 days for 4 weeks. A taxonomic analysis of the composition of the microbiota every 6h in the mice with jet lag showed that these animals had a reduced number of bacterial taxonomic units. Moreover, the dysbiosis worsened after 16 weeks of study. The same authors conducted a similar study in 2 healthy volunteers. A taxonomic stool analysis was made 1 day before the time change, during the jet lag (variation of 8–10h) and after recovery (2 weeks after landing). Gut microbiome samples obtained during jet lag showed a higher relative representation of Firmicutes, that was reversed after jet lag resolved. These studies, then, suggest that the alteration of the circadian rhythm is associated with alterations in the gut microbiome. In a recent study, a simulation of night shift work in a murine model showed significant changes in the gut microbiome that induced metabolic alterations, such as insulin resistance.16

We should also mention, of course, that the gut microbiome exerts multidimensional influences on many, if not all, brain functions and, consequently, changes that occur in the microbiome are likely to affect the quality and quantity of sleep.17,18

In conclusion, there is evidence of a two-way relationship between sleep disorders and changes in the gut microbiome that induces potential metabolic, cardiovascular, and neurocognitive changes in the patient. Although these implications appear to be clearer in obstructive sleep apnea,19 the possibility exists that sleep disturbances associated with other prevalent respiratory diseases can play a negative role in the evolution of patients, especially those with comorbidities, and this may be fruitful area for further investigation.

D. Chen, Z. Yin, B. Fang.
Measurements and status of sleep quality in patients with cancers.
Support Care Cancer, 26 (2018), pp. 405-414
W.T. McNicholas, J. Verbraecken, J.M. Marin.
Sleep disorders in COPD: the forgotten dimension.
Eur Respir Rev, 22 (2013), pp. 365-375
A.J. Piper, A.S. BaHammam, S. Javaheri.
Obesity hypoventilation syndrome: choosing the appropriate treatment of a heterogeneous disorder.
Sleep Med Clin, 12 (2017), pp. 587-596
C. Benedict, H. Vogel, W. Jonas, A. Woting, M. Blaut, A. Schümann, et al.
Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals.
Mol Metab, 5 (2016), pp. 1175-1186
S.L. Zhang, L. Bai, N. Goel, A. Bailey, C.J. Jang, F.D. Bushman, et al.
Human and rat gut microbiome composition is maintained following sleep restriction.
Proc Natl Acad Sci U S A, 114 (2017), pp. E1564-E1571
J.R. Anderson, I. Carroll, M.A. Azcarate-Peril, A.D. Rochette, L.J. Heinberg, C. Peat, et al.
A preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adults.
Sleep Med, 38 (2017), pp. 104-107
F. Bauters, E.R. Rietzschel, K.B. Hertegonne, J.A. Chirinos.
The link between obstructive sleep apnea and cardiovascular disease.
Curr Atheroscler Rep, 18 (2016), pp. 1
V.A. Poroyko, A. Carreras, A. Khalyfa, A.A. Khalyfa, V. Leone, E. Peris, et al.
Chronic sleep disruption alters gut microbiota induces systemic and adipose tissue inflammation and insulin resistance in mice.
Sci Rep, 6 (2016), pp. 35405
D. Gozal, Z. Qiao, I. Almendros, J. Zheng, A. Khalyfa, B. Shimpukade, et al.
Treatment with TUG891, a free fatty acid receptor 4 agonist, restores adipose tissue metabolic dysfunction following chronic sleep fragmentation in mice.
Int J Obes (Lond), 40 (2016), pp. 1143-1149
L. Kheirandish-Gozal, E. Peris, Y. Wang, M. Tamae Kakazu, A. Khalyfa, A. Carreras, et al.
Lipopolysaccharide-binding protein plasma levels in children: effects of obstructive sleep apnea and obesity.
J Clin Endocrinol Metab, 99 (2014), pp. 656-663
K. Miyazaki, N. Itoh, S. Yamamoto, S. Higo-Yamamoto, Y. Nakakita, H. Kaneda, et al.
Dietary heat-killed Lactobacillus brevis SBC8803 promotes voluntary wheel-running and affects sleep rhythms in mice.
Life Sci, 111 (2014), pp. 47-52
R.S. Thompson, R. Roller, A. Mika, B.N. Greenwood, R. Knight, M. Chichlowski, et al.
Dietary prebiotics and bioactive milk fractions improve NREM sleep, enhance REM sleep rebound and attenuate the stress-induced decrease in diurnal temperature and gut microbial alpha diversity.
Front Behav Neurosci, 10 (2017), pp. 240
R.M. Voigt, C.B. Forsyth, S.J. Green, E. Mutlu, P. Engen, M.H. Vitaterna, et al.
Circadian disorganization alters intestinal microbiota.
F. Bishehsari, A. Saadalla, K. Khazaie, P.A. Engen, R.M. Voigt, B.B. Shetuni, et al.
Light/dark shifting promotes alcohol-induced colon carcinogenesis: possible role of intestinal inflammatory milieu and microbiota.
Int J Mol Sci, 17 (2016), pp. E2017
C.A. Thaiss, D. Zeevi, M. Levy, E. Segal, E. Elinav.
A day in the life of the meta-organism: diurnal rhythms of the intestinal microbiome and its host.
Gut Microbes, 6 (2015), pp. 137-142
A. Khalyfa, V.A. Poroyko, Z. Qiao, A. Gileles-Hillel, A.A. Khalyfa, M. Akbarpour, et al.
Exosomes and metabolic function in mice exposed to alternating dark-light cycles mimicking night shift work schedules.
Front Physiol, 8 (2017), pp. 882
J.M. Krueger, M.R. Opp.
Sleep and microbes.
Int Rev Neurobiol, 131 (2016), pp. 207-225
A.C. Reynolds, J.L. Paterson, S.A. Ferguson, D. Stanley, K.P. Wright Jr., D. Dawson.
The shift work and health research agenda: considering changes in gut microbiota as a pathway linking shift work, sleep loss and circadian misalignment, and metabolic disease.
Sleep Med Rev, 34 (2017), pp. 3-9
N. Farré, R. Farré, D. Gozal.
Sleep apnea morbidity: a consequence of microbial-immune cross-talk?.
pii: S0012-3692(18)30405-7 (in press)

Please cite this article as: Farré N, Gozal D. Sueño y microbioma: una relación bidireccional. Arch Bronconeumol. 2019;55:7–8.

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