Gut Bacteria, Anxiety, and Depression in Inflammatory Bowel Disease: What a Major Research Review Found

Table of Contents

• Key Points
• Background: Why This Research Matters
• How the Researchers Conducted the Review
• Overview of the Included Studies
• Gut Microbial Diversity and Psychological Symptoms
• Specific Bacteria Linked to Anxiety and Depression
• How Gut Bacteria Function Differently
• What the Randomized Trials Showed
• What This Means for Patients
• Limitations: What the Review Could Not Prove
• Recommendations and Future Research
• Frequently Asked Questions
• Source Information

Key Points

• A review of ten studies involving 1,040 IBD patients found anxiety and depressive symptoms consistently linked to lower gut microbial diversity.
• Links to more pro-inflammatory bacteria and fewer short-chain fatty acid-producing bacteria held after accounting for inflammation and in patients in remission.
• Trials of probiotics and fecal microbiota transplantation changed gut microbial composition and reduced anxiety and depression scores, but results were not uniform.
• The review could not establish causality; cohort studies showed associations, and only large randomized trials can test causal hypotheses.
• Talk to your gastroenterologist or mental health provider about psychological symptoms; they are a recognized part of IBD care.

Background: Why This Research Matters

Inflammatory bowel disease (IBD) is a group of conditions marked by repeated episodes of chronic intestinal inflammation. The two main forms are ulcerative colitis (UC), which affects the inner lining of the large intestine, and Crohn's disease (CD), which can affect any part of the digestive tract.

IBD is becoming more common worldwide. The rise is especially notable in industrialized countries and in newly industrializing regions. The disease is also appearing at younger ages.

Modern drug therapy, including biologic medications, has greatly improved IBD outcomes. Even so, many patients still experience anxiety and depression. These psychological symptoms occur far more often in people with IBD than in the general population.

These symptoms matter for more than emotional well-being. They reduce quality of life and make patients less likely to follow their treatment plans. They may also worsen intestinal inflammation through the neuro-microbe axis, a communication network linking the nervous system and gut bacteria. This can create a vicious cycle.

Research on the gut–brain axis has revealed that gut bacteria play an important role in regulating mood and brain function. Many laboratory and clinical studies suggest that an imbalance in gut bacteria, called dysbiosis, may contribute to anxiety and depression-like behaviors. Dysbiosis may do this by affecting neurotransmitter metabolism (the processing of brain signaling chemicals), inflammatory responses, and the activity of the hypothalamic-pituitary-adrenal axis, the body's central stress response system.

Altered gut bacterial composition has also been widely reported in IBD patients. These changes include reduced microbial diversity and an increase in specific bacterial groups. They are closely tied to disease activity and to the severity of psychological symptoms.

Clinical studies on gut bacteria and IBD-related anxiety and depression are increasing. These studies include randomized controlled trials (RCTs, trials in which participants are assigned by chance to different treatments). These studies also include prospective cohort studies (studies that follow a group of people forward in time). Interventions studied include probiotics, prebiotics, fecal microbiota transplantation (FMT, transferring stool from a healthy donor into a patient's gut), and dietary changes.

However, study designs, bacterial detection methods, psychological assessment tools, and patient groups have varied widely. As a result, different studies have reached conflicting conclusions, and a systematic quantitative analysis has been lacking.

This systematic review aimed to bring together evidence from RCTs and prospective cohort studies. The authors assessed the links between microbiota-targeted interventions, gut bacterial characteristics, and symptoms of anxiety and depression in IBD patients. According to the authors, this is the first systematic review to combine evidence from both RCTs and prospective cohort studies on this topic. By joining clinical and microbiological data, the review may help clarify the role of the gut–brain axis in the psychological symptoms that accompany IBD. It may also support individualized treatment strategies, psychological management, and future research.

How the Researchers Conducted the Review

The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study was registered on the PROSPERO International Systematic Reviews Registry under the identifier CRD420251166542.

The researchers searched six electronic databases: PubMed, Embase, the Cochrane Library, Web of Science, EBSCOhost, and Scopus. The search covered records from each database's start date through October 17, 2025. Only studies published in English were considered.

The main search terms included "Inflammatory Bowel Diseases," "Crohn Disease," "Ulcerative Colitis," "Gastrointestinal Microbiome," "Microbiota," "Depression," "Anxiety," "Mood Disorders," and "Stress, Psychological." The researchers combined these terms using the Boolean operator "AND." They combined related terms within each concept (IBD, gut microbiota, and anxiety/depression) using "OR."

Studies were eligible if they met five criteria:

1. The study was a human study, a cohort study, or a randomized controlled trial.
2. The population was adults diagnosed with IBD.
3. The study examined how anxiety or depression affects the gut microbiota in IBD, or how the gut microbiota affects anxiety or depressive symptoms.
4. The outcomes included at least one of the following: the occurrence of anxiety and depression, their progression, or gut-related biomarkers of that progression.
5. The publication was a peer-reviewed full-text article.

The researchers excluded duplicate publications, studies with unavailable full texts or high risk of bias, and reviews, observational studies, case reports, letters to editors, and conference abstracts.

Two reviewers screened titles and abstracts, then screened full texts against the inclusion and exclusion criteria. The two reviewers worked independently. They resolved disagreements by discussion. In total, 10 studies were included in the full-text review.

Two other reviewers independently extracted data from the 10 studies using Excel. The extracted data covered study information (first author, publication year, country, study design, and sample size). The extracted data covered participant characteristics (including age and IBD type). The extracted data covered gut microbiota assessment methods and biomarkers. The extracted data covered outcomes (baseline occurrence and progression of anxiety and depression).

Two additional reviewers independently assessed risk of bias using the Critical Appraisal Skills Programme (CASP) checklist. For cohort studies, the assessment focused on the validity of the results, the nature of the results, and the local applicability of the findings. Local applicability means whether the results could be applied to the relevant clinical setting or population. For randomized controlled trials, the assessment focused on study design, methodological quality, results, and local applicability. Each checklist item was answered as "yes," "no," or "not sure." A high number of "not sure" responses meant the reliability of the study findings should be interpreted with caution. The applicability score was the number of "yes" responses divided by the total number of checklist questions for each study. A higher score indicated better study quality. Disagreements between reviewers were resolved through discussion.

The researchers initially planned a quantitative meta-analysis, a statistical method that pools results from multiple studies into a single estimate. They would have performed this analysis if at least two studies reported comparable exposures or interventions, microbiota-related outcomes, psychological outcomes, and extractable effect estimates. After full-text assessment and data extraction, the researchers judged quantitative synthesis infeasible. The reason was substantial clinical, methodological, and statistical heterogeneity (variation) across the included studies.

The included studies differed markedly in several ways:

• Study design, IBD subtype, disease activity status, exposure or intervention type, comparator definition, and follow-up duration
• Intervention strategies, which included probiotics, fecal microbiota transplantation, cognitive behavioral interventions, mindfulness-based interventions, and usual care comparisons
• Microbiota-related outcomes, which were assessed using alpha diversity, beta diversity, specific bacterial taxa, microbiome health indices, microbial dysbiosis indices, predicted or measured functional pathways, bile acid profiles, metabolomic signatures, and proteomic features
• Psychological outcome measures, which included the Hospital Anxiety and Depression Scale (HADS), the Self-Rated Anxiety Scale (SAS), the Self-Rated Depression Scale (SDS), the Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder Scale-7 (GAD-7), the Depression Anxiety Stress Scales (DASS), the Perceived Stress Scale (PSS), and quality-of-life-related scales

These differences prevented direct harmonization of outcome measures. Statistical reporting also varied substantially. Many studies reported the direction of association, taxon-specific differences, correlations, or multi-omics signatures. However, the studies did not consistently report standardized effect sizes, standard errors, confidence intervals, or enough raw data for recalculation. As a result, no single exposure–outcome or intervention–outcome comparison included enough statistically comparable studies to generate a reliable pooled estimate.

Therefore, the researchers did not calculate pooled effect sizes. They also did not perform I² statistics (a measure of inconsistency between studies), subgroup analyses, sensitivity analyses, or publication bias assessment. These analyses were not appropriate for the available evidence. Instead, the study used a structured descriptive synthesis approach. The researchers summarized findings by study design, microbiota domain, psychological outcome, intervention type, statistical reporting, and evidence direction. They presented the consistency and limitations of the available evidence in both tables and text.

Overview of the Included Studies

The review included 10 studies in total. Six were prospective cohort studies, and four were randomized controlled trials. Together, these studies involved 1,040 patients with IBD, including both ulcerative colitis and Crohn's disease.

The cohort studies mainly examined associations between gut microbiota characteristics and symptoms of anxiety and/or depression. The RCTs evaluated the effects of microbiota-related interventions on microbial composition and psychological outcomes.

The six prospective cohort studies were:

• Chen et al. (2021), China
• Feng et al. (2022), China
• Humbel et al. (2020), Switzerland
• Scaldaferri et al. (2023), Italy
• Thomann et al. (2022), Germany
• Yuan et al. (2021), China

The four randomized controlled trials were:

• Ewais et al. (2021)
• K et al. (2024)
• Liu et al. (2025)
• Shang et al. (2023)

The researchers also created a standardized evidence summary table. This table allowed comparison of the main microbiota-related findings, psychological outcomes, statistical reporting, and evidence direction across studies.

Gut Microbial Diversity and Psychological Symptoms

Across multiple cohort studies, reduced gut microbial alpha diversity was associated with anxiety and depressive symptoms in IBD patients. Alpha diversity is a measure of how many different types of bacteria live in the gut and how evenly they are distributed.

Scaldaferri et al. (2023) reported lower Shannon and Chao indices in ulcerative colitis patients with elevated anxiety or depression scores. These indices are mathematical measures of microbial diversity. Lower values indicated reduced microbial richness and evenness.

Similarly, Chen et al. (2021) observed significantly lower microbial diversity in ulcerative colitis patients with depression than in those without depression. Feng et al. (2022) reported comparable findings in Crohn's disease patients with psychological symptoms.

However, not all studies showed consistent results. Thomann et al. (2022) found no significant association between alpha diversity and depression or fatigue. That study also found no significant association with inflammatory markers, although microbial functional profiles were clearly altered.

Specific Bacteria Linked to Anxiety and Depression

Distinct microbial signatures appeared in IBD patients with anxiety or depression. In ulcerative colitis, Scaldaferri et al. (2023) reported increased abundance of pro-inflammatory and opportunistic taxa (bacterial groups). These included Enterobacteriaceae, Streptococcus, Veillonella, Klebsiella, and Clostridiaceae. In contrast, butyrate-producing bacteria, such as Ruminococcaceae and Roseburia, were reduced. Butyrate is a short-chain fatty acid that helps maintain gut health.

Similarly, Chen et al. (2021) found increased Proteobacteria, Enterobacteriaceae, and Escherichia–Shigella in depressed ulcerative colitis patients. These changes were accompanied by decreased Firmicutes, Clostridia, and Roseburia.

In Crohn's disease, Feng et al. (2022) reported a positive correlation between Ruminococcus gnavus abundance and anxiety/depression scores. In other words, higher levels of this bacterium went together with more severe psychological symptoms. That study also observed depletion of beneficial taxa, including Faecalibacterium prausnitzii.

Yuan et al. (2021) further identified disease-specific associations. Depression in Crohn's disease was linked to increased Bifidobacterium, whereas anxiety in ulcerative colitis was associated with elevated Desulfovibrio.

Humbel et al. (2020) studied 171 IBD patients in remission in Switzerland. That study reported several findings:

• A higher level of perceived stress was associated with lower alpha diversity.
• Anxiety and depression were significantly associated with beta diversity (differences in the overall composition of bacterial communities between people).
• A decrease in Clostridia, Bacilli, Bacteroidia, and Beta/Gamma-proteobacteria was associated with psychological distress.
• A decrease in Lachnospiraceae, Ruminococcaceae, and Veillonellaceae was correlated with anxiety and depression.
• An increase in Bifidobacterium (in Crohn's disease) and Desulfovibrio (in ulcerative colitis) was correlated with depression.
• An increase in Sutterella, RF32, and Lactococcus was correlated with quality of life in Crohn's disease.

Yuan et al. (2021) also studied 240 ulcerative colitis patients with active disease in China. That study found that patients with depression or anxiety showed lower microbial richness and diversity. These patients also had increased Lactobacillales, Sellimonas, Streptococcus, and Enterococcus, and decreased Prevotella_9 and Lachnospira. In addition, they had elevated glycochenodeoxycholate (a bile acid) and decreased 2'-deoxy-D-ribose and L-pipecolic acid (metabolites, or small molecules produced during metabolism). They also had reduced immunoglobulin proteins (immune proteins). In a laboratory experiment, giving 2'-deoxy-D-ribose and L-pipecolic acid preventively reduced depressive-like behaviors in mice with colitis.

Thomann et al. (2022) studied 62 patients with Crohn's disease and ulcerative colitis in Germany. That study found that depression was associated with lower abundance of Odoribacter, Alistipes, and Anaerotruncus, and with reduced pectin and glycosaminoglycan metabolism. Fatigue was associated with lower Intestinimonas, Eubacterium, Anaerotruncus, and Clostridiales genus incertae sedis, and with altered amino acid and carbohydrate metabolism.

How Gut Bacteria Function Differently

Functional analyses suggested that psychological symptoms were associated with changes in the metabolic potential of gut bacteria. In other words, the bacteria present were not just different in type, but also different in what chemical tasks they could perform.

Thomann et al. (2022) reported that depression was linked to reduced abundance of Odoribacter species involved in pectin degradation. Fatigue was associated with changes in amino acid metabolism and the pentose phosphate pathway, a series of chemical reactions in cells.

Feng et al. (2022) identified associations between anxiety/depression and disrupted bile acid metabolism. These changes included reduced secondary bile acids and elevated serum 7-dehydrocholic acid in Crohn's disease patients. The study also reported that fecal HDCA and 12-DHCA were inversely correlated with depression scores, while serum 7-DHCA was positively correlated with depression scores. Fecal TDCA, TLCA, and TβMCA were positively correlated with anxiety scores.

Using a multi-omics approach (combining data from genes, proteins, and metabolites), Yuan et al. (2021) reported associations involving gut microbiota, metabolites, and immunoglobulin profiles in active ulcerative colitis patients with anxiety and depression. These findings suggest that metabolic and immune-related pathways may contribute to psychological symptoms. These pathways may go beyond a simple reflection of disease activity.

However, the researchers cautioned that this evidence should be interpreted carefully. The included studies differed in how they defined disease activity, which inflammatory markers they measured, and how they adjusted their analyses.

What the Randomized Trials Showed

Evidence from randomized controlled trials showed that microbiota-targeted interventions modulated microbial composition and reduced anxiety and depression scores. These interventions included probiotics and fecal microbiota transplantation.

Studies that combined psychological interventions with microbiota profiling also suggested potential effects on gut microbial composition. However, the findings across trials remained heterogeneous, meaning they did not all point in the same direction or show the same size of effect.

The review did not report pooled effect sizes for these trials. The reason is that the trials used different interventions, different comparison groups, and different psychological measurement scales. This variation prevented the researchers from combining the results into a single statistical estimate.

What This Means for Patients

The current evidence supports a close and potentially bidirectional association between gut microbiota dysbiosis and anxiety and depression in IBD patients. "Bidirectional" means the relationship may work in both directions: psychological symptoms may affect the gut bacteria, and gut bacteria may affect psychological symptoms.

This finding matters for patients because it suggests that anxiety and depression in IBD are not simply a reaction to living with a chronic illness. Biological pathways involving gut bacteria may also play a role.

One of the most important findings is that the associations persisted after researchers adjusted for inflammatory markers. The associations were also observed when analyses were restricted to patients in remission. This suggests that the links between gut bacteria and psychological symptoms may not be fully explained by disease activity alone.

Both microbiota-targeted interventions and psychological therapies may represent promising strategies for managing psychological comorbidities in IBD. A comorbidity is a condition that occurs alongside another condition.

However, the researchers emphasized that the findings remain heterogeneous. Not every study found the same bacterial changes or the same psychological benefits. This means patients should not expect a single probiotic or supplement to reliably treat anxiety or depression.

Limitations: What the Review Could Not Prove

The review had several important limitations. First, the researchers could not perform a quantitative meta-analysis. The included studies differed too much in design, patient populations, interventions, and outcome measures.

Second, the studies used many different tools to measure anxiety and depression. These included HADS, SAS, SDS, PHQ-9, GAD-7, DASS, PSS, and quality-of-life scales. These differences prevented direct comparison of results across studies.

Third, statistical reporting varied substantially. Many studies reported only the direction of association, taxon-specific differences, correlations, or multi-omics signatures. They did not consistently report standardized effect sizes, standard errors, confidence intervals, or enough raw data for recalculation. As a result, no single comparison included enough statistically comparable studies to generate a reliable pooled estimate.

Fourth, the researchers did not perform I² statistics, subgroup analyses, sensitivity analyses, or publication bias assessment. These analyses were not appropriate for the available evidence.

Fifth, the total number of patients was relatively small. The 10 studies together included 1,040 patients with IBD. Individual cohort studies ranged from 39 patients (Feng et al., 2022, and Scaldaferri et al., 2023) to 240 patients (Yuan et al., 2021).

Sixth, the studies differed in disease activity definitions and inflammatory markers. Some studies included patients with active disease, some included patients in remission, and some included both. This variation makes it harder to draw firm conclusions.

Finally, the review could not establish causality. The cohort studies showed associations, but associations do not prove that gut bacteria cause anxiety or depression. Only large, well-designed randomized trials can test causal hypotheses.

Recommendations and Future Research

The researchers concluded that future large-scale, standardized longitudinal studies and randomized controlled trials are warranted. Longitudinal studies follow patients over time. These studies are needed to clarify directionality, meaning whether gut changes come before or after psychological symptoms.

Future research should also test causal hypotheses and develop personalized intervention approaches. Personalized approaches would tailor treatment to each patient's specific gut bacterial profile and psychological symptoms.

For patients, the practical takeaways are:

1. Anxiety and depression are common in IBD and are linked to measurable changes in gut bacteria.
2. These links appear even when IBD is in remission, so psychological symptoms deserve attention regardless of disease activity.
3. Probiotics and fecal microbiota transplantation showed promise in trials, but results were not consistent enough to recommend them as standard treatment for anxiety or depression in IBD.
4. Psychological therapies may also affect gut microbial composition, suggesting a two-way relationship worth discussing with your care team.
5. Talk to your gastroenterologist or mental health provider about psychological symptoms. They are a recognized part of IBD care, not a separate issue.

The review was registered on PROSPERO (identifier CRD420251166542), which means its methods were documented in advance. This registration helps ensure transparency and reduces the risk of bias in how studies were selected and analyzed.

Frequently Asked Questions

What did this review find about gut bacteria and anxiety or depression in IBD?

The review combined ten studies of 1,040 IBD patients. It found anxiety and depressive symptoms were consistently linked to lower gut microbial diversity, more pro-inflammatory bacteria, and fewer short-chain fatty acid-producing bacteria. These links held even after researchers accounted for inflammation and even in patients whose IBD was in remission.

Does this mean my gut bacteria cause my anxiety or depression?

No. The review could not establish causality. The cohort studies showed associations, but associations do not prove that gut bacteria cause anxiety or depression. The evidence supports a close and potentially bidirectional association, meaning the relationship may work in both directions, but only large, well-designed randomized trials can test causal hypotheses.

I have IBD and feel anxious. Is that common, and is it taken seriously?

Yes. Anxiety and depression occur far more often in people with IBD than in the general population. They reduce quality of life and make patients less likely to follow treatment plans. They are a recognized part of IBD care, not a separate issue, so talk to your gastroenterologist or mental health provider about psychological symptoms.

Did probiotics or fecal microbiota transplantation help anxiety and depression in these studies?

Trials of probiotics and fecal microbiota transplantation changed gut microbial composition and reduced anxiety and depression scores, but results across studies were not uniform. The review did not report pooled effect sizes because trials used different interventions, comparison groups, and psychological scales. Patients should not expect a single probiotic or supplement to reliably treat anxiety or depression.

My IBD is in remission but I still feel depressed. Does that fit these findings?

Yes. The associations between gut bacteria and psychological symptoms were observed when analyses were restricted to patients in remission. This suggests the links may not be fully explained by disease activity alone. Psychological symptoms deserve attention regardless of disease activity, so discuss them with your care team even when your IBD is quiet.

What bacteria were linked to anxiety and depression in these studies?

Specific signatures appeared. In ulcerative colitis, studies reported increased Enterobacteriaceae, Streptococcus, Veillonella, Klebsiella, and Clostridiaceae, with reduced butyrate-producing Ruminococcaceae and Roseburia. In Crohn's disease, one study found higher Ruminococcus gnavus correlated with worse anxiety and depression scores, and depletion of Faecalibacterium prausnitzii. Not every study found the same changes.

What are the limitations of this review?

The review could not perform a quantitative meta-analysis because studies differed too much in design, populations, interventions, and outcome measures. Statistical reporting varied, and the total number of patients was relatively small at 1,040 across ten studies. The review could not establish causality, and findings remain heterogeneous, so firm conclusions are limited.

When should a patient with IBD and anxiety or depression seek a second opinion?

A second opinion can help when anxiety or depression accompanies IBD, especially if symptoms persist while the disease is in remission. Gut microbial diversity is consistently lower in IBD patients with anxiety and depressive symptoms, and these links remain after adjusting for inflammation. Probiotics and fecal microbiota transplantation changed microbial composition and reduced symptom scores in trials, but results were not uniform, so they are not standard treatment for anxiety or depression in IBD. A second opinion can clarify whether psychological symptoms are being addressed as part of IBD care. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: Gut microbiota alterations associated with anxiety and depression in inflammatory bowel disease: a systematic review of prospective cohorts and randomized trials.

Authors: Zhang T, Wang L, Ren Z, Man R, Cheng X, Wang L, Wang J, Bu X, Yu Y.

Author affiliations: Liaoning University of Traditional Chinese Medicine, Shenyang, China; Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China; Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China; Second Affiliated Hospital, Liaoning University of Traditional Chinese Medicine, Shenyang, China.

Journal: Frontiers in Microbiology, volume 17, article 1853009.

Publication details: Received 11 April 2026; revised 05 May 2026; accepted 14 May 2026; published 02 June 2026. DOI: 10.3389/fmicb.2026.1853009.

Systematic review registration: PROSPERO, identifier CRD420251166542.

Note: This patient-friendly article is based on peer-reviewed research. It restructures one published systematic review for a general audience. It is not medical advice. Patients with inflammatory bowel disease who experience anxiety or depression should discuss their symptoms with a qualified healthcare provider.