Sleep deprivation (SD) refers to the partial or complete loss of sleep caused by various external or internal factors, resulting in the inability to meet the body's normal physiological sleep needs. A survey conducted in China once revealed that approximately 75% of respondents had experienced sleep disturbances.
Sleep deprivation is closely associated with a wide range of diseases, including cardiovascular diseases, respiratory disorders, neurological conditions, immune system dysfunctions, and gastrointestinal diseases. Among these, one often overlooked consequence is that “poor sleep” may lead to gut microbiota imbalance, which can trigger intestinal inflammation.
The gut is considered the cornerstone of human health. It is not only known as “the body’s largest waste treatment plant” but also regarded as “the body’s largest fueling station.” Therefore, gut health largely determines overall physical well-being. A healthy gut requires its resident microbial community—including beneficial bacteria, harmful bacteria, and neutral bacteria—to exist in a balanced and harmonious state.
The journal Advanced Science (Weinh) has recently published an online research article titled "Nicotinamide Mononucleotide Ameliorates Sleep Deprivation‐Induced Gut Microbiota Dysbiosis and Restores Colonization Resistance against Intestinal Infections."
This study, conducted through mouse experiments, found that sleep deprivation impairs the colonization of beneficial gut microbiota and disrupts the microbial homeostasis within the mouse intestine. However, supplementation with Nicotinamide Mononucleotide (NMN) helps counteract these negative effects, promoting the restoration of gut microbial balance and enhancing resistance to intestinal infections.
The researchers divided the mice into three groups: a Control Group (no sleep interference), an SD Group (sleep deprivation), and an SD+NMN Group (sleep deprivation with NMN supplementation).
For the SD groups, sleep deprivation was induced by placing the mice in a continuously rotating apparatus for three consecutive days, during which they were also orally administered pathogens to induce intestinal infection. Throughout these three days, the mice in the SD+NMN Group received an additional oral dose of 100 mg/kg of NMN to assess its potential protective effects against sleep deprivation-induced gut dysbiosis and infection.
01 Sleep deprivation impairs gut health and stability in mice, while NMN supplementation can reverse these adverse effects.
In the SD-treated mice, the fecal pathogen load was 10 to 1000 times higher than that of the control group, and their ability to clear the pathogens remained low even 48 hours after infection. Compared to the SD group, NMN supplementation significantly reduced the fecal loads of MRSA T144 and Escherichia coli B2.
Additionally, both SD groups exhibited colon atrophy and mucosal hyperemia, indicating structural damage and increased blood flow due to inflammation. However, these conditions were notably alleviated in the SD+NMN group, suggesting a protective effect of NMN.
The researchers also evaluated intestinal inflammatory responses based on histopathological features and the production of inflammatory factors. In the SD group, there was excessive lymphocyte infiltration in the gut tissue, while this inflammatory response was significantly mitigated in the SD+NMN group.
02 Sleep deprivation reduces the diversity of gut microbiota and alters its community structure, leading to microbial imbalance. NMN supplementation helps to restore and improve gut microbiota diversity, contributing to the recovery of a healthier and more balanced intestinal environment.
Additionally, the researchers analyzed the gut bacterial community diversity and composition across the groups. The results showed that mice subjected to sleep deprivation exhibited reduced microbial richness and abundance. In contrast, the NMN supplementation group showed the most significant improvement, with microbial diversity increasing by 13.17% compared to the control group (p = 0.0046).
Furthermore, Principal Component Analysis (PCA) indicated that sleep deprivation caused substantial structural changes in the fecal microbiota, while NMN supplementation largely restored the microbial community structure toward a state similar to that of the control group.
Specifically, the ratio of Firmicutes to Bacteroidetes, a key indicator of gut microbial ecological stability, was significantly affected. Compared to the control group:
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The SD group showed a 78.23% decrease in this ratio.
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The SD+NMN group showed a 74.95% decrease.
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In contrast, the NMN-only group showed only a 29.98% decrease, indicating a protective effect of NMN against SD-induced microbial imbalance.
03 NMN supplementation modulates the gut microbiota, which in turn helps to correct primary bile acid metabolism. This suggests that NMN not only restores microbial balance but also positively influences key metabolic pathways associated with intestinal and liver health, further contributing to overall metabolic homeostasis.
The researchers performed untargeted metabolomic analysis on fecal samples collected from the Control, SD, SD+NMN, and NMN groups to investigate whether changes in the gut microbiota could activate potential metabolic pathways.
The results showed significant differences in the fecal metabolomic profiles between the Control and SD groups. Among 471 key differential metabolites, 168 were commonly present across all four groups. Specifically:
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302 differential metabolites were identified between the Control and SD groups.
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169 differential metabolites were detected between the SD and SD+NMN groups.
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Compared to the SD group, the SD+NMN group showed upregulation of 37 enriched differential metabolites and downregulation of 24 enriched differential metabolites.
Further analysis focusing on metabolites related to bile salt metabolism revealed that NMN supplementation modulates the gut microbiota, thereby helping to correct primary bile acid metabolism. This finding suggests that NMN not only restores microbial balance but also positively influences host metabolic functions, particularly those involving bile acids critical for digestion and metabolic regulation.
In this study, the researchers confirmed that sleep deprivation impacts the composition of the gut microbiota and downstream secondary metabolites, and they explored whether these changes play a key role in the development of intestinal infections, as well as the potential influence of NMN in this process. The results demonstrated that sleep deprivation indeed harms gut health in mice, but this condition can be effectively improved through NMN supplementation.
Previous studies have also evaluated sleep in populations aged 45 to 75 years to determine whether NMN can improve sleep quality. The findings showed that NMN supplementation significantly reduced the time required for elderly individuals to fall asleep and increased their duration of deep sleep. This suggests that NMN may help counteract the decline in sleep quality associated with aging.
In summary, NMN supplementation not only helps mitigate gut health issues caused by poor sleep but also addresses the root cause by improving sleep quality itself. This dual benefit makes NMN a promising approach for helping individuals maintain better overall health.