Published online Sep 19, 2026. doi: 10.5498/wjp.121171
Revised: May 28, 2026
Accepted: June 26, 2026
Published online: September 19, 2026
Processing time: 121 Days and 20.7 Hours
Depression and poor sleep quality in patients with irritable bowel syndrome (IBS) represent a clinical syndrome associated with neurological damage caused by IBS. This condition significantly affects the quality of life and recovery of the patients, but the mechanism is currently unclear. Recent studies have shown that serum inflammatory indicators play an important role in the occurrence and develop
Core Tip: This minireview innovatively summarizes the correlation between serum inflammatory markers and the occurrence of depression and sleep disorders in patients with irritable bowel syndrome. It specifically focuses on interleukin-6, tumor necrosis factor-α, and interleukin-8, highlighting the crucial role of the gut-brain axis and systemic inflammation in this process. The review proposes that monitoring and targeting these inflammatory indicators could offer new strategies for preventing and treating these common irritable bowel syndrome comorbidities.
- Citation: Zhu SY, Fu Y, Li JZ, Zhang Z, Wang THS, Hu J, Li J. Review of serum inflammatory markers linked to depression and sleep quality in irritable bowel syndrome patients. World J Psychiatry 2026; 16(9): 121171
- URL: https://www.wjgnet.com/2220-3206/full/v16/i9/121171.htm
- DOI: https://dx.doi.org/10.5498/wjp.121171
Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by changes in bowel habits and symptoms such as abdominal pain and bloating. Epidemiological studies[1] show that the global prevalence of IBS ranges from 9% to 20%, and in China, the incidence of IBS accounts for approximately 7%-11%, with diarrhea-type IBS being the most common clinical form, accounting for 74% of all IBS cases. In addition to depression, IBS patients often present with emotional disorders such as anxiety and somatization symptoms. These psychological factors and intestinal symptoms are mutually reinforcing, significantly affecting patients’ quality of life and treatment compliance. Currently, the patho
Psychological disorders such as stress, anxiety or depression often co-occur with IBS and may exacerbate the severity of the disease in IBS patients. The results of a meta-analysis[3] show that the prevalence of anxiety disorders among IBS patients is around 35.00%. The relationship between IBS and depressive state is mainly mediated by the “gut-brain axis”, a bidirectional, neuro-hormonal communication system, and is interconnected between the gut and the brain through the autonomic nervous system, the hypothalamus-pituitary-adrenal axis, and the microbiome. Genetic susceptibility, tra
Approximately 37.6% of IBS patients have sleep problems, including decreased sleep quality, shortened sleep duration, and frequent awakenings, etc.[3]. Previous studies have indicated[10] that the incidence of sleep disorders in IBS patients is higher compared to healthy individuals. Cong et al’s research[11] showed that the higher neuroticism level of IBS patients directly interferes with the continuity of their sleep and the depth of sleep stages; at the same time, the changes in the neural-brain-gut axis of IBS patients will affect the secretion rhythm of sleep-related hormones such as melatonin in patients, leading to sleep disorders in IBS patients[12]; moreover, IBS patients often have comorbidities such as anxiety and depression, which will over-activate the hypothalamic-pituitary-adrenal (HPA) axis and enhance the excitability of the sympathetic nervous system, resulting in changes in the sleep structure of IBS patients[13].
Serum inflammatory markers are closely related to inflammatory bowel diseases, IBS, ulcerative colitis, and other gastrointestinal disorders. Morales-Guzmán et al[14] conducted a study showing that the levels of tumor necrosis factor-α (TNF-α) and IL-6 in the serum of IBS patients were 658.95 pg/μL and 641.25 pg/μL higher than those of healthy individuals, respectively. Yan et al[15] further discovered that intervention with an acidic enema combined with α7 nicotinic acetylcholine receptor-mediated inflammatory pathways could inhibit the release of inflammatory factors such as IL-6, IL-8, TNF-α, and high-mobility group protein B1, thereby alleviating the abnormal intestinal function and depressive-like behaviors in IBS model rats. This provides a new potential target for the clinical treatment of IBS-related depressive symptoms. Additionally, Bai et al[16] pointed out that the low-grade inflammatory state in the intestines of IBS patients can promote the release of pro-inflammatory factors such as IL-6 and TNF-α, thereby triggering neuroinflammation and oxidative stress responses, which affect the plasticity of brain nerves and the functions of brain regions related to emotion regulation, ultimately leading to the depressive state of patients. These studies collectively suggest that serum inflammatory markers such as IL-6, TNF-α, and IL-8 can damage brain nerves through the “gut-brain axis” and play an important role in the pathophysiological process of depression in IBS patients. In addition to IL-6, TNF-α, and IL-8, recent studies have also focused on inflammatory markers such as C-reactive protein, IL-1β, and monocyte chemoattractant protein-1[17]. These markers may have synergistic or complementary effects with traditional indicators in the “gut-brain axis”, but there is currently a lack of systematic comparative studies.
The relationship between IL-6 and depression in IBS patients: IL-6 is a key messenger molecule that connects im
Relationship between TNF-α and depression in IBS patients: TNF-α is a key pro-inflammatory cytokine, which is closely related to intestinal barrier dysfunction, systemic chronic inflammation, neuroinflammation, neurotransmitter disorders, and dysfunction of the HPA axis. These factors are also closely associated with the occurrence and deve
Relationship between IL-8 and depression in IBS patients: IL-8 is an important member of the CXC chemokine family, which can reflect the activation degree of the intestinal mucosal immune system and the systemic inflammatory state of IBS patients. The research by Prospero et al[30] showed that the IL-8 level in IBS patients with emotional disorders such as depression was 1.19 times that of patients without depression; a study involving 47 IBS patients showed[25] that probiotic preparations could reduce the IL-8 content in the patient’s body, thereby reducing the depression score of IBS patients; Mengzhu et al[31] reported that electroacupuncture in IBS mice reduced IL-8 levels to 66.67% of the control group, thereby alleviating the central nervous system inflammation and ultimately regulating the depression mood of the mice; Olano et al[32] showed in their research that there was a significant negative correlation between the psychological state in the quality of life of IBS patients and the IL-8 level; Arzani et al[33] pointed out in their article that by inhibiting the excessive production of inflammatory factors such as IL-8, it could effectively improve the “brain-gut” axis function of IBS patients, thereby having a positive effect on the regulation of emotional disorders in IBS patients.
Exploring the treatment of depression in IBS patients from the perspective of IL-6 indicators: The low-level intestinal inflammation in IBS patients leads to a continuous increase in peripheral IL-6 levels. IL-6 can penetrate the blood-brain barrier or activate brain microglia through neural signals, triggering neuroinflammation. Zeng et al[22] proved through research that Siensan Decoction can reduce the IL-6 level in IBS mice to 38 pg/mL by enhancing intestinal barrier function, thereby regulating the central 5-HT and alleviating the depression-like behavior caused by stress in IBS mice. Previous studies have found[16] that drugs such as stigmasterol, quercetin, naringenin, luteolin, sinapine, neorangipipirin, baicalin, rhodiola glycosides and isoorientin can reduce the IL-6 level in patients with diarrhea-type IBS accompanied by anxiety and depression, thereby maintaining the stability of the patient's neurotransmitters and achieving a better effect in improving the depression symptoms; Shaikh and Kumar[34] research suggested that Bacillus subtilis can reduce the IL-6 level in IBS patients by 0.16 μg/mL and effectively reduce the depression score of IBS patients from 1.62 points to 0.6 points. Therefore, inhibiting the IL-6 level may become an effective treatment method for IBS patients with depression.
Exploring the treatment of depression in IBS patients from the perspective of TNF-α indicators: TNF-α can transmit inflammatory signals to the central nervous system through various pathways, leading to activation of microglia cells, changes in neurotransmitter metabolism, and decreased neuroplasticity, thereby causing symptoms such as depression. Zhang et al[35] conducted a study showing that Sancao Liangzong Decoction regulates the TLR4/Myd88/Nf-κb signaling pathway, reducing TNF-α levels, further inhibiting inflammatory responses, and improving the intestinal mucosal barrier function of mice with diarrhea-type IBS, thereby alleviating the depressive state of IBS mice. Zeng et al[22] reported that the TNF-α level of IBS mice decreased by approximately 140 pg/mL after taking Sisheng Decoction, thereby regulating the gut-brain axis and increasing the movement range, duration of movement, and sucrose preference of the mice, indicating that Sisheng Decoction effectively improved the depressive-like behavior of IBS-D mice. Martin et al[36] pointed out in their research that taking probiotics can control the TNF-α level of IBS patients, thereby increasing the levels of butyric acid and tryptophan to 1.59 times and 1.01 times that before treatment, ultimately leading to normalization of the activity of the amygdala and reducing the anxiety and depression scores of IBS patients. Based on the above studies, it can be seen that the immune-inflammatory pathway centered on TNF-α is an important factor for the disorder of the “brain-gut axis” leading to the co-occurrence of IBS and depression, providing theoretical basis and diversified strategies for the treatment of depression in clinical IBS patients.
Exploring the treatment of depression in IBS patients from the perspective of IL-8 indicators: IL-8 can affect the emotional status of IBS patients through various pathways such as influencing the blood-brain barrier and neural pathways. The research results of Zeng et al[22] suggest that Sishen San can reduce the level of IL-8 to 47.06% of the control group by regulating the TLR4/Myd88/NF-κB signaling pathway, thereby alleviating the intestinal inflammation and intestinal barrier in diarrhea-type IBS mice and achieving the effect of alleviating their depressive behavior; Wang et al[37] found that Changan Granules can reduce the level of IL-8 in patients by regulating the immune and inflammatory responses in the intestine, thereby regulating the secretion of 5-HT and better improving the emotional status of patients with diarrhea-type IBS; Wierzbicka et al[25] suggested that the combined treatment of polyphenol extract mixture, probiotics and hydrolyzed fiber for IBS patients can reduce the level of IL-8, thereby lowering the depression-related score of patients to 28 points. In conclusion, by dynamically monitoring the level of IL-8, better treatment options can be provided for IBS patients with depression, thus achieving more effective and personalized treatment for IBS depression.
Serum inflammatory markers are closely related to sleep disorders in IBS patients. Wang et al[38] pointed out in their article that intestinal flora imbalance activates the TLR4/NF-κB inflammatory signaling pathway in germ-free mice, leading to an increase in TNF-α levels in the patients’ bodies, thereby causing sleep deprivation in the mice; Skrobis et al[39] stated in their research that the increase in serum inflammatory markers such as TNF-α and IL-6 in IBS patients caused by excessive inflammation is related to psychological disorders such as sleep difficulties in the patients.
The impact of IL-6 on sleep quality in IBS patients: The research results of Lin et al[40] showed that by inhibiting the ODC1/NF-κB pathway, the level of IL-6 and visceral hypersensitivity could be reduced, thereby alleviating the nocturnal abdominal pain, bloating or discomfort symptoms caused by chronic stress in IBS rats, and effectively improving the long-term sleep quality. Liu et al[41] pointed out in their report that the activation of microglia can cause neuroinflammation in the body, raising the level of IL-6 in IBS patients to 2.93 pg/mL, and reducing the expression of BDNF in the hypothalamus and hippocampus, thereby causing sleep deprivation in mice. Yang and Jun[42] showed that by regulating the TLR4/Myd88/NF-κB pathway, the level of IL-6 in IBS patients could be reduced to 84.69% of the previous level, effectively improving the sleep efficiency of patients and reducing the sleep latency. Yuan et al[43] suggested that due to stress and dysbiosis factors in IBS patients, by activating the intestinal TLR4/Myd88/NF-κB pathways, the level of IL-6 could rise to 1.36 times the previous level, and may reach the brain via the blood-brain barrier or neural pathways, thereby inhibiting melatonin secretion, disrupting the normal sleep-wake rhythm, thereby causing a decline in the sleep quality of patients. Hajiani et al[44] suggested that using probiotic supplements for IBS patients could effectively lower their IL-6 levels, thereby effectively improving their quality of life scores and improving their sleep quality. IL-6 plays an important role in the improvement of sleep quality in IBS patients, and in the future, by controlling the IL-6 level of IBS patients, better sleep improvement effects can be achieved.
The impact of TNF-α on sleep quality in IBS patients: Zeng et al[22] conducted a study showing that by reducing the expression level of TNF-α to 50.00% of the control group, promoting the expression of tight junction proteins, and inhibiting the TLR4/Myd88 signaling pathway, it could alleviate the inflammatory response in mice, protect the intestinal barrier, and alleviate sleep disorders in the diarrhea-type IBS mouse model. Deng et al[45] suggested that by down-regulating the expression level of TNF-α to 700 ng/mL, it could regulate the levels of short-chain fatty acids and 5-HT in IBS mice, thereby inhibiting visceral allergic reactions and ultimately improving the sleep quality of IBS mice. Onisor et al[46] pointed out in their research that after treatment with a TNF-α monoclonal antibody, PHQ-9 scores decreased significantly, indicating improved psychological health, which may contribute to better sleep quality. Choi et al[47] suggested that by improving the inflammation and damage of the IBS mouse tissues, the level of TNF-α could be reduced by 35 pg/mL compared to the blank control group, and effectively relieve their pain, thereby alleviating sleep quality problems caused by pain. Wierzbicka et al[25] stated that the combined intervention of probiotics and hydrolyzed fibers could effectively improve the mood and mental health of IBS patients by controlling the expression level of TNF-α within a lower range of 7-16 pg/mL and increasing the production of beneficial short-chain fatty acids, thereby improving their sleep quality. All these studies indicate that in the future, by regulating the level of TNF-α in the bodies of IBS patients, new treatment directions for improving the sleep quality of IBS patients can be provided.
The impact of IL-8 on sleep quality in IBS patients: IL-8 is a key pro-inflammatory chemokine. The research results of Valibouze et al[48] suggest that chitosan-dextran can reduce the IL-8 gene expression level in IBS mice by 98.00% compared to the control group, exerting better visceral pain relief and anti-inflammatory effects, thereby reducing and improving the decline in sleep quality caused by IBS symptoms such as abdominal pain and bloating. Wierzbicka et al[25] found that specific probiotic strains treatment can effectively reduce the IL-8 level in IBS patients to 40.0 pg/mL, thereby effectively improving the sleep quality of IBS patients. Nilholm et al[49] suggested that reducing the IL-8 level in IBS patients to 90.81% of the control group can effectively improve their gastrointestinal symptoms and alleviate sleep disorders caused by gastrointestinal discomfort. Olano et al[32] pointed out in their research that IL-8 significantly affects the quality of life of IBS patients and subsequently affects their sleep quality. All these studies have demonstrated the impact of IL-8 on the sleep quality of IBS patients. In the future, new treatment plans to improve the sleep quality of IBS patients can be explored from the perspective of IL-8 levels.
Exploring methods to improve the sleep quality of IBS patients from the perspective of IL-6 indicators: The study by Yang and Jun[42] showed that insomnia cognitive behavioral therapy could reduce the IL-6 level of IBS patients by 0.04 pg/mL, thereby effectively improving the sleep efficiency and quality of life of the patients. Weng et al[50] pointed out in their research that the PDIA3-STAT3 protein complex could down-regulate the IL-6 level to 320 pg/mL by mediating the CTSS/MHC-II pathway, which could effectively alleviate the organ hypersensitivity of IBS rats and thereby improve the sleep quality of the rats. Memel et al[51] showed in their research that foods rich in prebiotics and probiotics could effectively regulate the intestinal flora of IBS patients, thereby effectively reducing the secretion of inflammatory factors such as IL-6, and thus better achieving the effect of improving the sleep of patients. In the future, better treatment plans can be provided for IBS patients with sleep disorders by improving the IL-6 level of IBS patients.
Exploring methods to improve the sleep quality of IBS patients from the perspective of TNF-α indicators: Groeger et al[28] pointed out in their study that providing probiotic treatment to IBS patients can effectively reduce the TNF-α level of the patients, exerting a good anti-inflammatory effect, and ultimately effectively improving the psychological stress of IBS patients and enhancing their sleep quality. Yuan et al[43] showed in their research that melatonin, by regulating the TLR4/Myd88/NF-κB pathway, could lower the TNF-α level in diarrhea-type IBS rats to 140 pg/mg while also alleviating their visceral hypersensitivity, thereby regulating their sleep quality. Weng et al[50] suggested that punic acid could reduce the TNF-α level in IBS rats to 67.86% of the control group, thereby better improving the neuroinflammation and sleep quality of IBS rats. In conclusion, through the TNF-α pathway, new directions can be provided for improving the sleep quality of IBS patients.
Exploring methods to improve sleep quality in IBS patients from the perspective of IL-8: Previous studies have shown[49] that IBS patients can effectively control the production of inflammatory substances such as IL-8 through a low-starch and low-sugar diet, restore the intestinal homeostasis of IBS patients, and thereby better regulate the sleep quality of patients. Wierzbicka et al[25] conducted a study suggesting that the combined application of a polyphenol-rich extract mixture, probiotics, and hydrolyzed fibers reduced the IL-8 level in IBS patients by 16 pg/mL, thereby improving the intestinal-brain axis of patients and achieving the goal of improving their quality of life and sleep quality. Valibouze et al[48] also pointed out in their article that chitosan-glucan can effectively reduce the levels of inflammatory mediators such as IL-8 by 50%, thereby reducing visceral pain perception by 14%, and thereby improving sleep disorders caused by pain and other discomforts in IBS patients. By regulating the levels of inflammatory mediators such as IL-8 in IBS patients, it is expected to provide an effective way to alleviate the sleep problems of IBS patients.
Based on the aforementioned literature, this paper proposes an “inflammation-depression-sleep” triad model: In patients with IBS, the low-level inflammation in the gut activates peripheral and central inflammatory responses through the “gut-brain axis” (increased levels of IL-6, TNF-α, and IL-8)[16]. On the one hand, it induces depressive-related neuroinflammation and imbalance of neurotransmitters, and on the other hand, it interferes with sleep structure and melatonin secretion[50]. There is a bidirectional interaction between depression and sleep disorders, which further aggravates the inflammatory response and forms a vicious cycle. This model provides an integrated theoretical framework for future intervention strategies.
This article focuses on the serum inflammatory markers - IL-6, TNF-α, and IL-8, and explores the relationships between systemic chronic inflammation, neuroinflammation, the blood-brain barrier, and the “brain-gut axis” and the depression and sleep quality of IBS patients. It also elaborates on the roles of these three serum inflammatory markers in the occurrence and development of depression and sleep disorders in IBS patients, providing new directions for the treat
This minireview only elaborates the relationship between serum inflammatory indicators and depression and sleep quality in IBS patients from the three indicators of IL-6, TNF-α and IL-8, without involving potential related inflammatory markers such as IL-1β and C-reactive protein. Most of the literature consists of cross-sectional studies or animal ex
In the future, multicenter, prospective cohort studies will be carried out to verify the causal relationship between inflammatory markers and depression/sleep disorders. To explore the combination of multiple inflammatory indicators to construct a prediction model. Intervention trials targeting inflammatory pathways and combining neuroimaging to reveal the neural circuit mechanism of “inflammation-brain-behavior” should be carried out.
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