We previously reported greater reductions in depression and anxiety following probiotic supplementation in people with major depressive disorder (MDD) in a randomised double-blind placebo-controlled pilot trial (Nikolova et al., 2023). Here, we investigate the mechanisms underlying these effects.

49 people with MDD received a multi-strain probiotic (n = 24) or placebo (n = 25) for 8 weeks in addition to their antidepressant. Stool and blood samples were collected to analyse gut microbiota composition and inflammatory cytokines. Stool samples from 25 matched healthy volunteers (HVs) were also obtained.

Within the probiotic group, there was a significant increase in richness according to Chao1(bias-corrected) (w4 p = 0.04) and a trend for increased Total count (w4 p = 0.06, w8 p = 0.09) compared to baseline, but not to placebo. When compared to HVs post-treatment, only the placebo group had a significant decrease in Shannon' entropy (p = 0.03) and a trend for decreased Total count (p = 0.08) and Simpson's index (p = 0.09). Between-group differences in beta diversity were observed at week 4 (p = 0.04), but not week 8. Consistent between-group differences were seen in family Bacilleceae post-treatment (FDR p < 0.05), which correlated with decreases in anxiety (FDR p < 0.05). There were no differences in inflammatory markers.

This study was limited by data loss during the COVID-19 Pandemic.

Probiotics may positively impact the microbiota by normalising diversity and increasing levels of health-related taxa, which may partially account for their benefits in MDD. Understanding how these changes relate to symptom improvement can inform their targeted use in clinical practice. Larger trials incorporating functional multi-omics are needed.

NCT03893162.

Depression is a widespread disease affecting over 300 million individuals of various ethnicities and socioeconomic backgrounds globally. It frequently strikes early in life and becomes a chronic or recurring lifelong illness. Out of the various hypotheses for the pathophysiology of depression, the gut-brain axis and stress hypothesis are the ones that need to be researched, as psychological stress impairs one or more pathways of the brain-gut axis and is likely to cause brain-gut axis dysfunction and depression. A dysfunctional reciprocal gut-brain relationship may contribute to many diseases, including inflammatory disorders, abnormal stress responses, impaired behavior, and metabolic changes. The hormone ghrelin is a topic of interest concerning the gut-brain axis as it interacts with the gut-brain axis indirectly via the central nervous system or via crossing the blood-brain barrier. Ghrelin release is also affected by the gut microbes, which has also been discussed in the review. This review elaborates on Ghrelin's role in depression and its effect on various aspects like neurogenesis, HPA axis, and neuroinflammation. Furthermore, this review focuses on ghrelin as a potential target for alleviation of depressive symptoms.

For a long time, traditional medicine has acknowledged the gut's impact on general health. Contemporary science substantiates this association through investigations of the gut microbiota, the extensive community of microorganisms inhabiting our gastrointestinal system. These microscopic residents considerably improve digestive processes, nutritional absorption, immunological function, and pathogen defense. Nevertheless, a variety of gastrointestinal and extra-intestinal disorders can result from dysbiosis, an imbalance of the microbial composition of the gut microbiota. A groundbreaking discovery is the gut-brain axis, a complex communication network that links the enteric and central nervous system (CNS). This bidirectional communication allows the brain to influence gut activities and vice versa, impacting mental health and mood disorders like anxiety and depression. The gut microbiota can influence this communication by creating neurotransmitters and short-chain fatty acids, among other biochemical processes. These factors may affect our mental state, our ability to regulate our emotions, and the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to explore the complex interrelationships between the brain and the gut microbiota. We also conducted a thorough examination of the existing understanding in the area of how microbiota affects social behaviors, including emotions, stress responses, and cognitive functions. We also explored the potential of interventions that focus on the connection between the gut and the brain, such as using probiotics to treat diseases of the CNS. This research opens up new possibilities for addressing mental health and neurological conditions in an innovative manner.

The study aimed to comprehensively analyze and establish a framework for evaluating the efficacy of microbiome-targeted treatment (MTT) for depression.

We searched PubMed, Embase, Cochrane Library, Web of Science, and the Chinese National Knowledge Infrastructure database for randomized controlled trials (RCTs) on MTT in treating depression until October 19, 2023. A meta-analysis was conducted to evaluate the efficacy and safety of MTT. Comprehensive subgroup analyses were undertaken to explore factors influencing MTT's efficacy in treating depression. This study was registered with PROSPERO (CRD42023483649).

The study selection process identified 51,570 studies, of which 34 met the inclusion criteria. The overall pooled estimates showed that MTT significantly improved depression symptoms (SMD -0.26, 95% CI [-0.32, -0.19], I2 = 54%) with acceptable safety. Subgroup analyses by geography showed that effectiveness was demonstrated in Asia (SMD -0.46, 95% CI [-0.56, -0.36], I2 = 36%), while no evidence of effectiveness was found in Europe (SMD -0.07, 95% CI [-0.19, 0.05], I2 = 55%), America (SMD -0.33, 95% CI [-0.67, 0.02], I2 = 60%), and Oceania (SMD 0.00, 95% CI [-0.18, 0.18], I2 = 0%). Besides, the efficacy was shown in depressed patients without comorbidities (SMD -0.31, 95% CI [-0.40, -0.22], I2 = 0%), whereas effectiveness was poor in those with digestive disorders, such as irritable bowel syndrome (SMD -0.37, 95% CI [-0.89, 0.16], I2 = 74%), chronic diarrhea (SMD -0.34, 95% CI [-0.73, 0.05]), and chronic constipation (SMD -0.23, 95% CI [-0.57, 0.11], I2 = 0%). In perinatal depressed patients, MTT was not effective (SMD 0.16, 95% CI [0.01, 0.31], I2 = 0%). It was found that < 8 weeks (SMD -0.33, 95% CI [-0.45, -0.22], I2 = 0%) and 8-12 weeks (SMD -0.34, 95% CI [-0.44, -0.23], I2 = 57%) MTT were effective, while > 12 weeks (SMD 0.02, 95% CI [-0.12, 0.17], I2 = 68%) MTT was ineffective.

Despite the overall effectiveness of MTT in treating depression and its acceptable safety profile, caution is warranted in drawing this conclusion due to limitations posed by the small sample size of included studies and heterogeneity. The efficacy of MTT for depression exhibits variation influenced by geography, patient comorbidities, and duration of administration.

Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.

There is a growing body of evidence implicating gut-brain axis dysfunction in the pathophysiology of mood disorders. Accordingly, gut microbiota has become a promising target for the development of biomarkers and novel therapeutics for bipolar and depressive disorders.

We describe the observed changes in the gut microbiota of patients with mood disorders and discuss the available studies assessing microbiota-based strategies for their treatment.

Microbiota-targeted interventions, such as symbiotics, prebiotics, paraprobiotics, and fecal microbiota transplants seem to attenuate the severity of depressive symptoms. The available results must be seen as preliminary and need to be replicated and/or confirmed in larger and independent studies, also considering the pathophysiological and clinical heterogeneity of mood disorders.

The use of prebiotics and probiotics as a treatment for psychiatric conditions has gained interest due to their potential to modulate the gut-brain axis. This review aims to assess the effectiveness of these interventions in reducing symptoms of depression and anxiety in psychiatric populations.

The aim was to comprehensively review and appraise the effectiveness of prebiotic, probiotic, and synbiotic interventions in reducing clinical depression and anxiety symptoms.

Systematic searches were conducted across Embase, Medline, PsycINFO, CINAHL, Cochrane Library, and Science Citation Index from database inception to May 22, 2023.

Randomized controlled trials investigating prebiotic, probiotic, or synbiotic interventions for treating clinical depression or anxiety symptoms in clinical samples were included. Data were extracted on study characteristics, intervention details, and outcome measures. The Cochrane Collaboration Tool was used to assess the risk of bias.

The standardized mean difference (SMD) was calculated using Hedge's g as the metric of effect size. A random-effects model was applied to estimate pooled effect sizes with 95% CIs. Subgroup analyses were performed based on study characteristics, methodological factors, and intervention types. Sensitivity analyses excluded studies with a high risk of bias.

Twenty-three RCTs involving 1401 patients met the inclusion criteria, with 20 trials providing sufficient data for meta-analysis. Of these, 18 trials investigated probiotics for depression, 9 trials assessed probiotics for anxiety, and 3 trials examined prebiotics for depression. Probiotics demonstrated a significant reduction in depression symptoms (SMD: -0.96; 95% CI: -1.31, -0.61) and a moderate reduction in anxiety symptoms (SMD: -0.59; 95% CI: -0.98, -0.19). Prebiotics did not show a significant effect on depression (SMD: -0.28; 95% CI: -0.61, 0.04). High heterogeneity was observed across studies, and subgroup analyses indicated that study duration and probiotic formulations contributed to the variation in effect sizes.

Probiotics showed substantial reductions in depression symptoms and moderate reductions in anxiety symptoms. Prebiotics showed a nonsignificant trend toward reducing depression. An adjunctive mental health treatment approach that diagnoses, monitors, and treats the gut microbiome alongside traditional pharmacological treatment holds promise for clinical practice.

PROSPERO registration no. CRD42023424136.

Probiotic augmentation offers a promising treatment for bipolar disorder (BD) and schizophrenia spectrum disorder (SSD). By targeting microbiome deviations, they may improve both gut and brain health.

In this double-blind, randomized, placebo-controlled trial with the multi-strain probiotic formulation Ecologic BARRIER, we aimed to improve psychiatric and cognitive symptoms, intestinal permeability, and gastrointestinal symptoms in patients with BD or SSD. A total of 131 patients were randomized 1:1 to receive either the probiotic supplement (n = 67) or a placebo (n = 64) for 3 months, in addition to treatment-as-usual. The primary outcomes were symptom severity assessed by the Brief Psychiatric Rating Scale and cognitive functioning by the Brief Assessment of Cognition in Schizophrenia.

No significant effect of probiotics was observed on psychiatric symptoms, but borderline significant improvement was observed in the cognition category of verbal memory (Linear Mixed Model (LMM) 0.33; adjusted P = .059). Probiotics beneficially affected markers of intestinal permeability and inflammation, including zonulin (LMMserum = -18.40; adjusted P = .002; LMMfecal = -10.47; adjusted P = .014) and alpha-1 antitrypsin (LMM 9.26; adjusted P = .025). Indigestion complaints significantly decreased in male participants in the probiotics group (LMM = -0.70; adjusted P = .010). Adverse events were similar between groups.

Our study observed significant advantages of probiotics for gut health in BD and SSD, with excellent safety and tolerability. A borderline effect on verbal memory was also indicated. These results underscore the need for further research into microbiome-targeted interventions for patients with complex brain disorders.

Small intestinal bacterial overgrowth (SIBO) is a gastrointestinal condition characterized by abnormal colonization of bacteria in the small intestine, leading to overgrowth and alteration, which is linked to gastrointestinal issues, potentially affecting neurological and mental health. Despite existing research, we still do not understand how SIBO affects tryptophan metabolism and psychiatric diseases. We investigated the literature for connections between SIBO, tryptophan metabolism disruptions, and psychiatric disorders like autism, schizophrenia, Alzheimer's, and Parkinson's diseases. We also explored the interaction between thyroid disorders and their influence on SIBO and psychiatric illnesses. PubMed and Google Scholar databases were searched using keywords and phrases, individual and in combinations, like "SIBO," "gut microbiota," "neurologic disorders," "mental disorders," "tryptophan," "dopamine," and "thyroid disease." We focused on original research and review papers that presented empirical studies conducted on animal models and human subjects published in English between February 1992 to February 2023. The initial 2 634 534 records were preliminary screened based on title and abstract and then subjected to full-text review to exclude publications with insufficient data on SIBO, lack of a psychiatric disorder component, or methodological limitations compromising the integrity of the findings. The analysis highlights the significance of the association between psychiatric disorders and SIBO, emphasizing the role of gut-microbial diversity in mental health. We advocate for more detailed studies, including longitudinal research, to clarify the causal relationships between SIBO, gut dysbiosis, and psychiatric disorders and for an integrated approach while treating complex psychiatric conditions.

Although diabetic peripheral neuropathic pain (DPNP) and depression have been recognized for many years, their co-morbidity relationship and effective treatment choices remain uncertain.

To evaluate the antidepressant effect of carvedilol on streptozotocin-induced DPNP mice, and the relationship with gut microbiota.

The hyperalgesia and depressive behaviors of mice with comorbidity of DPNP and depression were confirmed by pain threshold of the mechanical sensitivity test (MST), immobility time of the tail suspension test (TST) and the forced swimming test (FST). The anti-depressive effect and fecal gut microbiota composition were studied in DPNP mice treated with carvedilol (10 mg/kg/day), and the relationships between them were analyzed by Spearman's correlation.

Depression was successfully induced in DPNP mice. Carvedilol can reverse the decreased mechanical pain threshold and relieve the depressive behaviors of DPNP mice, while increasing the abundance of Prevotella, Ruminococcus, Helicobacter and Desulfovibrio, and decreasing the abundance of Akkermansia and Allobaculum.

Carvedilol can alleviate the mechanical hyperalgesia and alter gut microbiota to ameliorate the depression-like behaviors which induced by DPNP.

Currently, depression-induced suicide has emerged as the primary contributor to the worldwide burden of disability. However, the prevailing drug treatment not only suffers from delayed effectiveness and limited efficacy, but also there are withdrawal symptoms and rebound phenomenon. Consequently, there is an imperative to investigate safer and more efficient treatments to ameliorate the clinical manifestations of depression. At present, there is increased evidence that probiotics can improve the symptoms of depression, but the existing studies use many and mixed types of probiotics, and it is impossible to determine the specific efficacy of bifidobacteria in the treatment of depression. This review will systematically review the effects of bifidobacteria on the treatment effect of depression, Meta-analysis showed that Bifidobacterium-related preparations effectively improved depressive symptoms in patients with depression. This study represents the initial meta-analysis conducted on the use of bifidobacteria-related agents for treating depression. The objective was to determine the effect of bifidobacteria-related preparations on improving depressive symptoms. We found that Bifidobacterium and its related agents can effectively reduce depression scale scores in patients with depression, suggesting the need for further research into this potential strategy for the prevention and treatment of depression.

The intestinal microbiota is a complex ecosystem that not only affects various physiological functions, such as metabolism, inflammation and the immune response, but also has an important effect on the development of tumors and response to treatment. The detection of intestinal flora enables the timely identification of disease-related flora abnormalities, which has significant implications for both disease prevention and treatment. In the field of basic and clinical research targeting gut microbiome, there is a need to recognize and understand the laboratory assays for gut microbiomics. Currently, there is no unified standard for the experimental procedure, quality management and report interpretation of intestinal microbiome assay technology. In order to clarify the process, the Tumor and Microecology Committee of China Anti-Cancer Association and the Tumor and Microecology Committee of Hubei Provincial Immunology Society organized relevant experts to discuss and put forward the standard technical specifications for gut microecomics laboratories, which provides a basis for further in-depth research in the field of intestinal microecomics.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine (TCM) formula primarily utilized for treating gut disorders. GQD showed therapeutic effects on several diseases in clinical and animal studies by targeting gut microbes. Our recent studies also found that GQD efficiently alleviated anxiety in methamphetamine-withdrawn mice via regulating gut microbiome and metabolism. Given that various studies have indicated the link between the gut microbiome and the development of depression, here we endeavor to explore whether GQD can manage depression disorders by targeting the gut microbiome.

The depression-like model was induced in rats through chronic unpredictable mild stress (CUMS) and the depression levels were determined using the sucrose preference test (SPT). To address the depression-like behavior in rats, oral administration of GQD was employed. The colon microbiome and metabolite patterns were determined by 16s rRNA sequencing and untargeted metabolomics, respectively.

We found 6 weeks of CUMS can induce depression-like behavior in rats and 4 weeks of GQD treatment can significantly alleviate the depression-like behavior. GQD treatment can also ameliorate the histological lesions in the colon of CUMS rats. Then, CUMS increased the abundance of gut microbes, while GQD treatment can restore it to a lower level. We further discovered that the abundances of 19 bacteria at the genus level were changed with CUMS treatment, among which the abundances of Ruminococcus, Lachnoclostridium, Pygmaiobacter, Bacteroides, Pseudomonas, and Pseudomonas Family_XIII_AD3011_group were stored by GQD treatment. Besides, we identified the levels of 36 colon metabolites were changed with CUMS treatment, among which the levels of Fasciculic acid B, Spermine, Fludrocortisone acetate, alpha-Ketoglutaric acid, 2-Oxoglutaric acid, N'-(benzoyloxy)-2-(2,2-dichlorocyclopropyl) ethanimidamide, N6-Succinyl Adenosine Oleanolic acid, KQH, Ergosta-5,7,9(11),22-Tetraen-3-beta-Ol, Gentisic acid, 4-Hydroxyretinoic Acid, FAHFA (3:0/16:0), Leucine-enkephalin and N-lactoyl-phenylalanine can be restored by GQD treatment.

Our findings provide evidence supporting the therapeutic efficacy of GQD in alleviating depression-like behavior in CUMS rats, potentially being targeted on colon bacteria (especially the abundance of Ruminococcus and Bacteroides) and metabolites (especially the level of Oleanolic acid).

Depression and anxiety are pervasive mental health disorders with substantial global burdens. Probiotics, live microorganisms known for their health benefits, have emerged as a potential therapeutic intervention for these conditions. This systematic review and meta-analysis aim to evaluate the strain-specific effects of probiotics on relieving depressive and anxiety symptoms while elucidating underlying mechanisms.

EMBASE, Cochrane CENTRAL and PubMed/Medline were systematically queried to identify studies released until May 15, 2024. Randomized Controlled Trials (RCTs) that employed standardized assessment tools for depression and anxiety namely Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Depression Anxiety Stress Scales (DASS), or Montgomery-Asberg Depression Rating Scale (MADRS) were included.

12 RCTs involving 707 participants were included. Seven RCTs utilizing the BDI questionnaire demonstrated a significant decrease in depressive symptoms favoring probiotics containing strains such as Lactobacillus acidophilus, Lactobacillus paracasei, Lactobacillus casei, Lactobacillus plantarum, Lactobacillus salivarius, Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium breve, and Bifidobacterium longum (MD: -2.69, CI95%: -4.22/-1.16, p value: 0.00). Conversely, RCTs using HAMD showed a non-significant reduction in depressive symptoms (MD: -1.40, CI95%: -3.29/0.48, p value: 0.14). RCTs employing DASS and MADRS scales also showed no significant differences.

This meta-analysis offers valuable insights into the strain-specific effects of probiotics containing Lactobacillus and Bifidobacterium species on depressive and anxiety symptoms. While our findings suggest a significant reduction in depressive symptoms based on the BDI scale favoring probiotics, the lack of significant effects observed on the HAMD, DASS, and MADRS scales underscores the complexity inherent in these conditions. It is imperative to acknowledge the mixed results across different measurement scales, indicating the need for cautious interpretation. Therefore, we advocate for a nuanced understanding of probiotics' impacts on various dimensions of mood, emphasizing the necessity for further research.

Gut microbiota is involved in intricate and active metabolic processes the host's brain function, especially its role in immune responses, secondary metabolism, and symbiotic connections with the host. Gut microbiota can promote the production of essential metabolites, neurotransmitters, and other neuroactive chemicals that affect the development and treatment of central nervous system diseases. This article introduces the relevant pathways and manners of the communication between the brain and gut, summarizes a comprehensive overview of the current research status of key gut microbiota metabolites that affect the functions of the nervous system, revealing those adverse factors that affect typical communication between the brain-gut axis, and outlining the efforts made by researchers to alleviate these neurological diseases through targeted microbial interventions. The relevant pathways and manners of communication between the brain and gut contribute to the experimental design of new treatment plans and drug development. The factors that may cause changes in gut microbiota and affect metabolites, as well as current intervention methods are summarized, which helps improve gut microbiota brain dialogue, prevent adverse triggering factors from interfering with the gut microbiota system, and minimize neuropathological changes.

The influence of gut microbiome, metabolites, omics, hormones, and stress on general and mental health is increasingly being recognized. Ancient cultures recognized the importance of diet and gut health on the overall health of an individual. Western science and modern scientific methods are beginning to unravel the foundations and mechanisms behind some of the ancient beliefs and customs. The gut microbiome, an organ itself, is now thought to influence almost all other organs, ranging from the brain to the reproductive systems. Gut microbiome, metabolites, hormones, and biological sex also influence a myriad of health conditions that range from mental health disorders, obesity, gastrointestinal disorders, and cardiovascular diseases to reproductive health. Here, we review the history and current understanding of the gut-brain axis bidirectional talk in various mental health disorders with special emphasis on anxiety and depressive disorders, whose prevalence has increased by over 50% in the past three decades with COVID-19 pandemic being the biggest risk factor in the last few years. The vagal nerve is an important contributor to this bidirectional talk, but other pathways also contribute, and most remain understudied. Probiotics containing Lactobacillus and Bifidobacterium species seem to have the most impact on improvement in mental health symptoms, but the challenge appears to be maintaining sustained levels, especially since neither Lactobacillus nor Bifidobacterium can permanently colonize the gut. Ancient endogenous retroviral DNA in the human genome is also linked to several psychiatric disorders, including depression. These discoveries reveal the complex and intricately intertwined nature of gut health with mental health disorders.

Intestinal microecology (IM) is the largest and most important microecological system of the human body. Furthermore, it is the key factor for activating and maintaining the physiological functions of the intestine. Numerous studies have investigated the effects of the gut microbiota on the different tissues and organs of the human body as well as their association with various diseases, and the findings are gradually being translated into clinical practice. The gut microbiota affects the occurrence, progression, treatment response, and toxic side effects of tumors. The deepening of research related to IM and tumors has opened a new chapter in IM research driven by methods and technologies such as second-generation sequencing and bioinformatics. The IM maintains the function of the host immune system and plays a pivotal role in tumor-control drug therapy. Increasing evidence has proven that the efficacy of tumor-control drugs largely depends on the IM balance, and strategies based on the IM technology show promising application prospects in the diagnosis and treatment of tumor. The Tumor and Microecology Professional Committee of the Chinese Anti-cancer Association gathered relevant experts to discuss and propose the "Chinese guidelines for integrated diagnosis and treatment of IM technologies in tumor application (2024 Edition)," which was established based on the research progress of the application of the IM technology in tumor to provide a basis for the standardization of the diagnosis and treatment of the IM technology in the tumor.

We recently indicated that four-week probiotic supplementation significantly reduced depression along with microbial and neural changes in people with depression. Here we further elucidated the biological modes of action underlying the beneficial clinical effects of probiotics by focusing on immune-inflammatory processes. The analysis included a total of N = 43 participants with depression, from which N = 19 received the probiotic supplement and N = 24 received a placebo over four weeks, in addition to treatment as usual. Blood and saliva were collected at baseline, at post-intervention (week 4) and follow-up (week 8) to assess immune-inflammatory markers (IL-1β, IL-6, CRP, MIF), gut-related hormones (ghrelin, leptin), and a stress marker (cortisol). Furthermore, transcriptomic analyses were conducted to identify differentially expressed genes. Finally, we analyzed the associations between probiotic-induced clinical and immune-inflammatory changes. We observed a significant group x time interaction for the gut hormone ghrelin, indicative of an increase in the probiotics group. Additionally, the increase in ghrelin was correlated with the decrease in depressive symptoms in the probiotics group. Transcriptomic analyses identified 51 up- and 57 down-regulated genes, which were involved in functional pathways related to enhanced immune activity. We identified a probiotic-dependent upregulation of the genes ELANE, DEFA4 and OLFM4 associated to immune activation and ghrelin concentration. These results underscore the potential of probiotic supplementation to produce biological meaningful changes in immune activation in patients with depression. Further large-scale mechanistic trials are warranted to validate and extend our understanding of immune-inflammatory measures as potential biomarkers for stratification and treatment response in depression. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.

Immune inflammation is one of the main factors in the pathogenesis of depression. It is an effective and active way to find more safe and effective anti-inflammatory depressant drugs from plant drugs. The purpose of this study is to explore the potential of marine plant Sargassum pallidum (Turn).C.Ag. (Haihaozi, HHZ) in the prevention and treatment of depression and to explain the related mechanism. Phytochemical analysis showed that alkaloids, terpenes, and organic acids are the main constituents. In vitro and in vivo activity studies showed the anti-neuroinflammatory and antidepressant effect of Sargassum pallidum, furthermore, confirmed that 7-Hydroxycoumarin, Scoparone, and Kaurenoic Acid are important plant metabolites in Sargasum pallidum for anti-neuroinflammation. Mechanism exploration showed that inhibition of ERK1/2/p38 inflammatory signaling pathway contributing to the antidepressant effect of Sargassum pallidum in reducing intestinal inflammatory levels. This study confirmed the value of Sargassum pallidum and its rich plant metabolites in anti-inflammatory depression, providing a new choice for the follow-up research and development of antidepressant drugs.

Heat stress (HS) commonly occurs as a severe pathological response when the body's sensible temperature exceeds its thermoregulatory capacity, leading to the development of chronic brain inflammation, known as neuroinflammation. Emerging evidence suggests that HS leads to the disruption of the gut microbiota, whereas abnormalities in the gut microbiota have been demonstrated to affect neuroinflammation. However, the mechanisms underlying the effects of HS on neuroinflammation are poorly studied. Meanwhile, effective interventions have been unclear. β-Hydroxybutyric acid (BHBA) has been found to have neuroprotective and anti-inflammatory properties in previous studies. This study aims to explore the modulatory effects of BHBA on neuroinflammation induced by HS and elucidate the underlying molecular mechanisms.

An in vivo and in vitro model of HS was constructed under the precondition of BHBA pretreatment. The modulatory effects of BHBA on HS-induced neuroinflammation were explored and the underlying molecular mechanisms were elucidated by flow cytometry, WB, qPCR, immunofluorescence staining, DCFH-DA fluorescent probe assay, and 16S rRNA gene sequencing of colonic contents.

Heat stress was found to cause gut microbiota disruption in HS mouse models, and TM7 and [Previotella] spp. may be the best potential biomarkers for assessing the occurrence of HS. Fecal microbiota transplantation associated with BHBA effectively reversed the disruption of gut microbiota in HS mice. Moreover, BHBA may inhibit microglia hyperactivation, suppress neuroinflammation (TNF-α, IL-1β, and IL-6), and reduce the expression of cortical endoplasmic reticulum stress (ERS) markers (GRP78 and CHOP) mainly through its modulatory effects on the gut microbiota (TM7, Lactobacillus spp., Ruminalococcus spp., and Prevotella spp.). In vitro experiments revealed that BHBA (1 mM) raised the expression of the ERS marker GRP78, enhanced cellular activity, and increased the generation of reactive oxygen species (ROS) and anti-inflammatory cytokines (IL-10), while also inhibiting HS-induced apoptosis, ROS production, and excessive release of inflammatory cytokines (TNF-α and IL-1β) in mouse BV2 cells.

β-Hydroxybutyric acid may be an effective agent for preventing neuroinflammation in HS mice, possibly due to its ability to inhibit ERS and subsequent microglia neuroinflammation via the gut-brain axis. These findings lay the groundwork for future research and development of BHBA as a preventive drug for HS and provide fresh insights into techniques for treating neurological illnesses by modifying the gut microbiota.

The prevalence of mental health issues among UK undergraduate students is growing, and poor diet quality appears to be a risk factor for poor mental health although with limited research in this area. Therefore, the objective of this study was to examine the cross-sectional associations between diet quality and common mental disorders (CMD) such as depression and anxiety in UK undergraduate students. A cross-sectional survey consisting of demographic information and validated questionnaires (the Short-Form Food Frequency Questionnaire [SFFFQ] and the Hospital Anxiety and Depression Scale [HADS]) was conducted to measure diet quality and anxiety and depression in young adults in 44 UK-based universities. Multiple regression analysis adjusting for confounding factors was used to assess the associations between them. Undergraduate university students (n = 202, 67% female) with a mean age of 20.9 ± 3.6 years and a mean body mass index (n = 170) of 22.6 ± 3.2 kg/m2 took part in the study. Prevalence of anxiety was high, with 40% of the sample having an anxiety score in the severe range (≥12 points) while the prevalence of depression was lower, with 6% of the population having a depression score in the severe range (≥12 points). Diet quality was significantly higher for females than males (p = 0.034) and was poor for 38% of the sample, being more common in males compared to females, although not significantly so (43% and 36%, respectively). Diet quality was inversely associated with anxiety (β = -0.427; p = 0.029) and was more likely to be associated with anxiety in females than males (β = 0.743; p = 0.043). No significant relationship between diet quality and depression was found. Better self-reported health, father's qualification and smoking status were also associated with less anxiety and depression. This research supports other research suggesting that UK universities should explore whether the implementation of dietary interventions and improving the food environment would be a cost-effective option to reduce the high prevalence of anxiety among students.

Migraine is a common and debilitating neurological disorder characterized by the recurrent attack of pulsating headaches typically localized on one side of the head associated with other disabling symptoms, such as nausea, increased sensitivity to light, sound and smell and mood changes. Various clinical factors, including the excessive use of migraine medication, inadequate acute treatment and stressful events, can contribute to the worsening of the condition, which may evolve to chronic migraine, that is, a headache present on >15 days/month for at least 3 months. Chronic migraine is frequently associated with various comorbidities, including anxiety and mood disorders, particularly depression, which complicate the prognosis, response to treatment and overall clinical outcomes. Emerging research indicates a connection between alterations in the composition of the gut microbiota and mental health conditions, particularly anxiety and depression, which are considered disorders of the gut-brain axis. This underscores the potential of modulating the gut microbiota as a new avenue for managing these conditions. In this context, it is interesting to investigate whether migraine, particularly in its chronic form, exhibits a dysbiosis profile similar to that observed in individuals with anxiety and depression. This could pave the way for interventions aimed at modulating the gut microbiota for treating difficult-to-manage migraines.

The effect of low-FODMAPs diet on irritable bowel syndrome (IBS) in Western China has not been reported. We aimed to investigate the effect of low-FODMAPs diet on IBS patients in the area and whether low-FODMAPs diet-induced alterations of microbiota could be improved through probiotics. IBS patients were randomized to the control group, low-FODMAPs diet group, probiotics group, or combined group. IBS Symptom Severity Score questionnaire (IBS-SSS) and IBS Quality of Life Score questionnaire (IBS-QOL) were completed at baseline, 2 and 4 weeks to evaluate the severity of symptoms. Fresh feces were collected for analyses of gut microbiota and short-chain fatty acids at baseline and 4 weeks after intervention. Seventy-three patients were included in the per protocol analysis. After intervention, there was significant improvement in IBS-SSS in the low-FODMAPs group (37.5%, 44.2%), probiotics group (51.4%, 62.0%), and combined group (34.1%, 40.4%) at both 2 weeks and 4 weeks, compared with the baseline (p < .05). In the low-FODMAPs group, the abundance of several microbiota (Lachnoclostridium, Enterococcus, etc.) was significantly decreased. Furthermore, after the supplementation of probiotics in the combined group, the abundance of Genus_Ruminococcus, Coprococcus, Acidaminococcus, Ruminiclostridium, Akkermansia, Eggerthella, and Oxalobacter was significantly increased, which was associated with the improvements of symptoms score in the Pearson correlation analysis. Our study confirmed the effectiveness and safety of short-term low-FODMAPs diet in IBS symptoms based on the Chinese diet in Western China. The combination of low-FODMAPs and probiotics plays a beneficial role in gut microbiota in IBS.

Depressive disorders are heterogeneous in nature, and their global reach makes them the cause of suffering for a million individuals worldwide. Standard treatment does not work for one in three people, and side effects can significantly reduce the quality of life. A multidisciplinary approach allows for a broader insight into the nature of the disease, given its complex etiology. One of its elements is the hypothesis of inflammation, which also accompanies obesity-related disease. Obesity and depression interact, causing many researchers to develop new non-pharmacological treatment methods for both diseases. One suggestion is physical exercises that have great potential to be used in clinical practice. They can exert changes on the central nervous system and thus modulate mood. Another is diet, which concentrates on active molecules that also affect the central nervous system (CNS). There is an urgent need to create appropriate criteria and recommendations that systematize existing knowledge and allow it to be used in practice. There is an urgent need to create appropriate criteria and recommendations that systematize existing knowledge and allow it to be used in practice.

With the increasing prevalence of age-related chronic diseases burdening healthcare systems, there is a pressing need for innovative management strategies. Our study focuses on the gut microbiota, essential for metabolic, nutritional, and immune functions, which undergoes significant changes with aging. These changes can impair intestinal function, leading to altered microbial diversity and composition that potentially influence health outcomes and disease progression. Using advanced metagenomic sequencing, we explore the potential of personalized probiotic supplements in 297 older adults by analyzing their gut microbiota. We identified distinctive Lactobacillus and Bifidobacterium signatures in the gut microbiota of older adults, revealing probiotic patterns associated with various population characteristics, microbial compositions, cognitive functions, and neuroimaging results. These insights suggest that tailored probiotic supplements, designed to match individual probiotic profile, could offer an innovative method for addressing age-related diseases and functional declines. Our findings enhance the existing evidence base for probiotic use among older adults, highlighting the opportunity to create more targeted and effective probiotic strategies. However, additional research is required to validate our results and further assess the impact of precision probiotics on aging populations. Future studies should employ longitudinal designs and larger cohorts to conclusively demonstrate the benefits of tailored probiotic treatments.

This review aims to argue how using probiotics can improve anxiety and depressive behaviour without adverse effects, also exploring the impact of postbiotics on it. Specifically, probiotics have drawn more attention as effective alternative treatments, considering the rising cost of antidepressant and anti-anxiety drugs and the high risk of side effects. Depression and anxiety disorders are among the most common mental illnesses in the world's population, characterised by low mood, poor general interest, and cognitive or motor dysfunction. Thus, this study analysed published literature on anxiety, depression, and probiotic supplementation from PubMed and Scopus, focusing on the last twenty years. This study focused on the effect of probiotics on mental health as they have drawn more attention because of their extensive clinical applications and positive impact on various diseases. Numerous studies have demonstrated how the gut microbiota might be critical for mood regulation and how probiotics can affect host health by regulating the gut-brain axis. By comparing the different works analysed, it was possible to identify a strategy by which they are selected and employed and, at the same time, to assess how the effect of probiotics can be optimised using postbiotics, an innovation to improve mental well-being in humans.

In this study, a systematic review of randomized clinical trials conducted from January 2000 to December 2023 was performed to examine the efficacy of psychobiotics-probiotics beneficial to mental health via the gut-brain axis-in adults with psychiatric and cognitive disorders. Out of the 51 studies involving 3353 patients where half received psychobiotics, there was a notably high measurement of effectiveness specifically in the treatment of depression symptoms. Most participants were older and female, with treatments commonly utilizing strains of Lactobacillus and Bifidobacteria over periods ranging from 4 to 24 weeks. Although there was a general agreement on the effectiveness of psychobiotics, the variability in treatment approaches and clinical presentations limits the comparability and generalization of the findings. This underscores the need for more personalized treatment optimization and a deeper investigation into the mechanisms through which psychobiotics act. The research corroborates the therapeutic potential of psychobiotics and represents progress in the management of psychiatric and cognitive disorders.

Correct nutrition and diet are directly correlated with mental health, functions of the immune system, and gut microbiota composition. Diets with a high content of some nutrients, such as fibers, phytochemicals, and short-chain fatty acids (omega-3 fatty acids), seem to have an anti-inflammatory and protective action on the nervous system. Among nutraceuticals, supplementation of probiotics and omega-3 fatty acids plays a role in improving symptoms of several mental disorders. In this review, we collect data on the efficacy of nutraceuticals in patients with schizophrenia, autism spectrum disorders, major depression, bipolar disorder, and personality disorders. This narrative review aims to provide an overview of recent evidence obtained on this topic, pointing out the direction for future research.

The comorbidity between diabetes mellitus and depression was revealed, and diabetes mellitus increased the prevalence of depressive disorder, which ranked 13th in the leading causes of disability-adjusted life-years. Insulin resistance, which is common in diabetes mellitus, has increased the risk of depressive symptoms in both humans and animals. However, the mechanisms behind the comorbidity are multi-factorial and complicated. There is still no causal chain to explain the comorbidity exactly. Moreover, Selective serotonin reuptake inhibitors, insulin and metformin, which are recommended for treating diabetes mellitus-induced depression, were found to be a risk factor in some complications of diabetes.

Given these problems, many researchers made remarkable efforts to analyze diabetes complicating depression from different aspects, including insulin resistance, stress and Hypothalamic-Pituitary-Adrenal axis, neurological system, oxidative stress, and inflammation. Drug therapy, such as Hydrogen Sulfide, Cannabidiol, Ascorbic Acid and Hesperidin, are conducive to alleviating diabetes mellitus and depression. Here, we reviewed the exact pathophysiology underlying the comorbidity between depressive disorder and diabetes mellitus and drug therapy.

The review refers to the available literature in PubMed and Web of Science, searching critical terms related to diabetes mellitus, depression and drug therapy.

In this review, we found that brain structure and function, neurogenesis, brain-derived neurotrophic factor and glucose and lipid metabolism were involved in the pathophysiology of the comorbidity. Obesity might lead to diabetes mellitus and depression through reduced adiponectin and increased leptin and resistin. In addition, drug therapy displayed in this review could expand the region of potential therapy.

The review summarizes the mechanisms underlying the comorbidity. It also overviews drug therapy with anti-diabetic and anti-depressant effects.

Diets rich in live microbes can bring various health benefits. However, the association between dietary live microbe intake and frailty has not been studied.

The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. A total of 11,529 participants were included. Sanders et al. classified the level of live microbes in foods into low (<104 CFU/g), medium (104-107 CFU/g), or high (>107 CFU/g). With the methodology of Sanders et al. and dietary questionnaire data, participants were divided into three groups: (1) low dietary live microbe intake group (only low-level foods), (2) medium dietary live microbe intake group (medium but not high-level foods), and (3) high dietary live microbe intake group (any high-level foods). Additionally, foods with medium and high live microbe content were aggravated as MedHi. Frailty index ≥0.25 is defined as frailty. The weighted logistic regression analysis was conducted to examine the relationship between the intake of dietary live microbe and frailty. The restricted cubic splines (RCS) were employed to detect the nonlinear relationships.

In the fully adjusted model, participants with high dietary intake of live microbe had a significantly lower risk of frailty than those with low dietary intake of live microbe (OR = 0.67, 95% CI: 0.56, 0.79). For every 100 grams of MedHi food consumed, the risk of frailty decreased by 11% (OR = 0.89, 95% CI: 0.85, 0.92) after adjusting all covariates. The RCS indicated the existence of non-linear relationships. For those who consumed less than 100 grams of MedHi, increasing MedHi intake may significantly reduce the risk of frailty, but after exceeding 100 grams, the curve gradually levels off.

Our results suggested that increasing dietary live microbe intake was associated with a lower risk of frailty. However, more research is needed to verify this.

Menopause is a natural physiological phase during which women experience dramatic hormonal fluctuations. These lead to many symptoms, such as depression and anxiety, which, in turn, can negatively affect quality of life. Proper nutrition has an influential role in alleviating depression as well as anxiety. It is well known that gut microbiota dysbiosis contributes to the development of mood disorder. There is mounting evidence that modulating the gut-brain axis may aid in improving mood swings. In this context, this narrative review summarizes recent findings on how aging changes the composition of the gut microbiota and on the association between gut microbiota and mood disorders. In addition, it evaluates the effectiveness of psychobiotics and fermented foods in treating mood swings in middle-aged and older women. A search was done using PubMed, Scopus, and Google Scholar, and thirteen recent articles are included in this review. It is evident that psychobiotic supplementation and fermented foods can improve mood swings via several routes. However, these conclusions are based on only a few studies in middle-aged and older women. Therefore, long-term, well-designed randomized controlled trials are required to fully evaluate whether psychobiotics and fermented foods can be used to treat mood swings in this population.

The effects of the gut microbiota on mental and intestinal health are an area of great interest. This study aimed to reveal the relationship between the intake of probiotic and prebiotic foods and mental and gut health. Data were obtained using an online survey from young adults (n = 538) enrolled at Afyonkarahisar Health Sciences University who agreed to participate in this study in the 2022-2023 academic year. This study included 538 participants, mostly (85.5%) females. Participants who never consumed yogurt had 7.614 times higher Gastrointestinal Symptom Rating Scale scores than those who consumed yogurt daily (p < 0.01). Similarly, the frequency of ayran consumption had a statistically significant effect on Bristol Stool Scale scores (p < 0.05). The ratio of normal defecation to constipation was 68.7% lower in participants who consumed ayran daily, whereas the ratio of diarrhea to constipation was 76.4% lower in participants who never consumed ayran. However, the frequency of prebiotic consumption did not have a significant effect on Bristol Stool Scale scores (p > 0.05). The consumption of probiotic and prebiotic foods exerted a significant effect on GSRS total scores and subfactors of the Depression Anxiety Stress Scale-42, namely depression, anxiety, and stress.

Changes in the gut microbiome can affect cognitive and psychological functions via the microbiota-gut-brain (MGB) axis. Probiotic supplements are thought to have largely positive effects on mental health when taken in sufficient amounts; however, despite extensive research having been conducted, there is a lack of consistent findings on the effects of probiotics on anxiety and depression and the associated microbiome alterations. The aim of our study is to systematically review the most recent literature of the last 10 years in order to clarify whether probiotics could actually improve depression and anxiety symptoms. Our results indicate that the majority of the most recent literature suggests a beneficial role of probiotics in the treatment of depression and anxiety, despite the existence of a substantial number of less positive findings. Given probiotics' potential to offer novel, personalized treatment options for mood disorders, further, better targeted research in psychiatric populations is needed to address concerns about the exact mechanisms of probiotics, dosing, timing of treatment, and possible differences in outcomes depending on the severity of anxiety and depression.

Functional dyspepsia is a common functional disorder of the gastrointestinal tract that is responsible for many primary care visits. No organic changes have been found to explain its symptoms. We hypothesize that modern lifestyles and environmental factors, especially psychological stress, play a crucial role in the high prevalence of functional dyspepsia and metabolic syndrome. While gastrointestinal tract diseases are rarely linked to metabolic disorders, chronic stress, obesity-related metabolic syndrome, chronic inflammation, intestinal dysbiosis, and functional dyspepsia have significant pathophysiological associations. Functional dyspepsia, often associated with anxiety and chronic psychological stress, can activate the neuroendocrine stress axis and immune system, leading to unhealthy habits that contribute to obesity. Additionally, intestinal dysbiosis, which is commonly present in functional dyspepsia, can exacerbate systemic inflammation and obesity, further promoting metabolic syndrome-related disorders. It is worth noting that the reverse is also true: obesity-related metabolic syndrome can worsen functional dyspepsia and its associated symptoms by triggering systemic inflammation and intestinal dysbiosis, as well as negative emotions (depression) through the brain-gut axis. To understand the pathophysiology and deliver an effective treatment strategy for these two difficult-to-cure disorders, which are challenging for both caregivers and patients, a psychosocial paradigm is essential.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease characterized by hyperandrogenism, ovulatory dysfunction, and ovarian polycystic changes, which combines with reproductive problems, metabolic disorders, and psychological disorders to exhibit a far-reaching impact on the physical and mental health of women. We reviewed previous research and discovered that psychiatric disorders are more common in PCOS patients and their children, potentially exacerbating the condition and creating a vicious loop. To understand the reasons, relevant articles were collected following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines from PubMed, Web of Science, and Cochrane Library, through December 2022. Evidence suggested that PCOS-related clinical manifestations, hyperandrogenism, insulin resistance, obesity, gut dysbiosis, and other variables may increase the risk of psychiatric disorders in patients. In turn, psychiatric disorders may aggravate the pathologic process of PCOS and increase the difficulty of the treatment. We systematically reported the mechanisms underlying the psychiatric disorders-PCOS interactions, intending to provide potential ways to break the vicious cycle and lay the groundwork for future research. However, research on PCOS and psychiatric disorders were still in initial stages, which limited the scope of this review. More studies are needed to further verify our findings.

The microbiome is a critical factor in health throughout human development. The aims of this scoping review are to (i) elucidate the differences between the youth (post-natal day 21-65 for rodents, 2-7 years for non-human primates, and 10-25 years for humans) microbiome with other life stages and (ii) identify youth-specific microbial changes associated with substance use.

Peer-reviewed studies published up to May 2023 were identified in PubMed and SCOPUS and included gut and oral microbiome studies from rodents, non-human primates, and humans (N = 1733). Twenty-six articles were determined eligible based on inclusion criteria (aim 1: n = 19, aim 2: n = 7).

The adolescent and young adult oral and gut microbiomes are distinct compared to other life stages, within both non-human and human models. While there is limited research in this area, the microbiome appears to be vulnerable to substance use exposure earlier in life, including substances commonly initiated and escalated during adolescence and young adulthood (i.e. alcohol, cannabis, and tobacco).

Studies across the lifespan indicate that adolescence and young adulthood are distinct periods of development, where the microbiome is sensitive to exposures, including substance use. There is a need for more studies focused on the adolescent and young adult microbiome and substance use, as well as focused on the oral microbiome during this developmental period. Understanding the gut and oral microbiome during adolescence and young adulthood may provide insight into the pathophysiology of substance use disorders.

Gut microbiota have crucial effects on brain function via the gut-brain axis. Growing evidence suggests that this interaction is mediated by signaling molecules derived from dietary components metabolized by the intestinal microbiota. Although recent studies have provided a substantial understanding of the cell-specific effects of gut microbial molecules in gut microbiome-brain research, further validation is needed. This review presents recent findings on gut microbiota-derived dietary metabolites that enter the systemic circulation and influence the cell-to-cell interactions between gut microbes and cells in the central nervous system (CNS), particularly microglia, astrocytes, and neuronal cells, ultimately affecting cognitive function, mood, and behavior. Specifically, this review highlights the roles of metabolites produced by the gut microbiota via dietary component transformation, including short-chain fatty acids, tryptophan metabolites, and bile acid metabolites, in promoting the function and maturation of brain cells and suppressing inflammatory signals in the CNS. We also discuss future directions for gut microbiome-brain research, focusing on diet-induced microbial metabolite-based therapies as possible novel approaches to mental health treatment.

To determine if cellulose nanofibrils (CNF) have potential applications as food additives.

Male C57BL/6 mice on a Western diet were exposed to CNF for one month at a dose of 30 mg/kg by gavage. Male NOD mice, a model for type 1 diabetes (T1D), were used in a six-month study.

Sequencing analysis of 16S rRNA genes suggested significant changes in gut microbiome of male C57BL/6 mice exposed to CNF. Analysis of functional metagenomics indicated that many of the functional contents that might be altered following CNF ingestion were associated with lipid and carbohydrate processing. Further studies in NOD mice suggested that there were some decreases in the blood glucose levels during the insulin tolerance test and glucose tolerance test following CNF treatment. However, these small decreases were not considered biologically meaningful as there were no significant changes in either the area under the curve or the first-order rate constant for glucose disappearance. Moreover, serum concentrations of cytokines/chemokines including IL-3, IL-12(p70) and the keratinocyte chemoattractant were increased following chronic exposure to CNF. In addition, behavioral studies suggested that the percentage of immobility time during the tail-suspension test was significantly increased following six months of exposure to CNF in NOD mice, signifying an increase in depression-related behavior.

Collectively, long-term CNF consumption was associated with changes in the ecology of the gut microbiome, immune homeostasis, and possibly energy metabolism and mental health in male NOD mice on a Western diet.