Gut Bacteria, Sleep, and Brain Health
Could gut microbiota be driving sleep disturbance and cognitive decline?
This paper is part of NMJ’s 2018 Cognition and Mental Health Special Issue. The article can be seen in context, along with the rest of the issues here.
Anderson JR, Carroll I, Azcarate-Peril MA, et al. A preliminary examination of gut microbiota, sleep, and cognitive flexibility in healthy older adults. Sleep Medicine. 2017;38:104-107.
To assess relationships between gut microbiota, sleep quality, and cognitive flexibility in healthy older adults.
A preliminary observational study
Data was analyzed from 37 participants, ranging in age from 50 to 85 years (73% female, 92% Caucasian). People with significant neurological or gastrointestinal conditions were excluded, as were those who had used probiotics or antibiotics within a 30-day period prior to the study. Presence of hypertension, diabetes, and sleep apnea were tracked as covariates, as well as dietary macronutrient intake per participant report (EPIC-Norfolk Food Frequency Questionnaire).
Self-reported sleep quality was assessed with the Pittsburg Sleep Quality Index (PSQI), which tracked sleep latency and duration. Higher scores on the PSQI indicate poorer quality of sleep. Cognitive flexibility was assessed through Stroop Color-Word testing. During Stroop testing, participants read color words (“Stroop Word”) aloud, identified the ink color of rows of Xs (“Stroop Color”), and identified the ink color of incongruent color words (“Stroop Color-Word”) as quickly as possible. Higher scores indicate more properly identified items. Gut microbiome samples were analyzed by uBiome, using 16S ribosomal RNA amplicon sequencing and reported as percentage of phyla present.
Controlling for covariates, reduced sleep quality correlated with poorer Stroop test results (Stroop Word, P=0.018; Stroop Color-Word, P=0.010, and Stroop Color, P=0.053). Again, controlling for covariates, the study revealed participants with higher percentage of Verrucomicrobia had improved cognitive flexibility, as measured by Stroop Word (P=0.034) and Stroop Color (P=0.071) testing. The Lentisphaerae phylum did not display a similar correlation; however, it did show a stronger relationship with Stroop Color-Word performance (P=0.015), independent of sleep quality.
As the surge in research of the microbiota suggests, the potential impact of the gut microbiota on our understanding of human health, and our approach to treating various health conditions, is massive. This particular study, while slightly convoluted by the number of variables discussed, along with its admitted limitations (eg, results based more on observation than causal relationship, lack of detailed screening measures for sleep, and superficial exploration into mechanism of action), does provide some interesting food for thought: Could gut microbiota be a factor connecting sleep quality and cognitive health?
Given that more than 30% of Americans report deficient sleep on a nightly basis, and an estimated 50 million to 70 million adults report a sleep disorder(1), continued exploration into modifiable factors is a necessity. The gut microbiome is a vastly uncharted territory, and our voyage into recognizing its implications on health demands is just beginning. The influence of the gut microbiome on human health must be more deeply understood. Observational studies, such as the one reviewed here, are the first steps in a direction that may ultimately help us harness manipulation of the microbiome for therapeutic use.
The researchers propose that their findings, along with those from other related studies(2-4) suggest sleep quality is directly proportional to presence of certain phyla of gut microbiota, which then correlate with cognitive function. Both phyla discussed in this paper were associated with disrupted sleep. The Verrucomicrobia was then directly correlated with cognition while Lentisphaerae was possibly indirectly correlated. The question not so clearly raised was if the cognitive impairment was a direct result of compromised gut flora, or if it was secondary to the chronic, noncommunicable health conditions also related to both, such as obesity, diabetes, and heart disease.
The researchers failed to discuss the potential reverse correlation, where poor microbiota proportions of the given phyla Lentisphaerae and Verrocumicrobia could be more directly causal to reduced sleep quality. We know that sleep quality is directly related to both chronic disease and cognitive decline; the Centers for Disease Control and Prevention show that adults who sleep less than 7 hours per night are more likely to report chronic health conditions compared to those who get enough sleep(5). Given the observational design of this study, it is not possible to draw direct cause-and-effect conclusions. However, with increased community recognition of the gut-brain connection, the relationship between these 2 variables should perhaps be considered dynamic and bidirectional.
The pronounced correlation shown in this study between the Verrucomicrobia and Lentisphaerae phyla and sleep quality contrasts with a 2016 study by Benedict and colleagues, which showed correlation with phyla other than these 2.2 Additionally, upon further investigation into the 2 aforementioned phyla, their associated genera and species are not part of the more commonly seen and prescribed probiotics today. All of this is to say that while this information is certainly fascinating, we are clearly in the very beginning of understanding how the microbiota of the gut may (or may not) affect sleep and cognition.
(1) American Sleep Association. Sleep and Sleep Disorder Statistics. https://www.sleepassociation.org/about-sleep/sleep-statistics/. Accessed March 6, 2018.
(2) Benedict C, Vogel H, Jonas W, et al. Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals. Mol Metab. 2016;5(12):1175-1186.
(3) Magnusson KR, Hauck L, Jeffrey BM, et al. Relationships between diet-related changes in the gut microbiome and cognitive flexibility. Neuroscience. 2015;300:128-140.
(4) Bruce-Keller AJ, Salbaum JM, Luo M, et al. Obese-type gut microbiota induce neurobehavioral changes in the absence of obesity. Biol Psychiatry. 2015;77(7):607-615.
(5) Centers for Disease Control and Prevention. Sleep and Sleep Disorders: Data and Statistics. https://www.cdc.gov/sleep/data_statistics.html. Updated May 2, 2017. Accessed March 6, 2018.