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Gut-brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease.
UNLABELLED: IntroductionInflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder characterised by inflammation of the gastrointestinal tract. There is a growing consensus that IBD is associated with anxiety- and depression-related symptoms. Psychological symptoms appear to be more prevalent during active disease states with no difference in prevalence between Crohn's disease and ulcerative colitis. Behavioural disturbances including anxiety- and depression-like symptoms have also been observed in animal models of IBD. RESULTS: The likely mechanisms underlying the association are discussed with particular reference to communication between the gut and brain. The close bidirectional relationship known as the gut-brain axis includes neural, hormonal and immune communication links. Evidence is provided for a number of interacting factors including activation of the inflammatory response system in the brain, the hypothalamic-pituitary-adrenal axis, and brain areas implicated in altered behaviours, changes in blood brain barrier integrity, and an emerging role for gut microbiota and response to probiotics in IBD.DiscussionThe impact of psychological stress in models of IBD remains somewhat conflicted, however, it is weighted in favour of stress or early stressful life events as risk factors in the development of IBD, stress-induced exacerbation of inflammation and relapse. CONCLUSION: It is recommended that patients with IBD be screened for psychological disturbance and treated accordingly as intervention can improve quality of life and may reduce relapse rates.
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Stress and mental health symptoms in early pregnancy are associated with the oral microbiome.
BACKGROUND: Research has revealed associations between microbes of the gastrointestinal tract and stress, anxiety and depression in pregnant or postpartum women. While these studies suggest a gut-brain-behaviour axis, no studies have examined microbes of the oral cavity in relation to maternal mental health. OBJECTIVE: To explore a potential oral-brain-behaviour axis related to maternal mental health. METHODS: Microbes were measured in saliva obtained from 224 second-trimester (mean±SD = 17±2 weeks) women oversampled for stress. Oralome data were associated with women's recent or cumulative pregnancy stress, trait and state anxiety, depression symptoms and post-traumatic stress disorder (PTSD) symptoms. Covariates explored included age, income, alcohol and tobacco use, dental issues and physical health problems. RESULTS: Pregnant women in the high trait anxiety or depression symptom groups had higher oral alpha diversity, indicating higher richness of species within samples. Groups with high and low PTSD symptoms differed in beta diversity, reflecting differences in community composition. Linear discriminant analysis showed differently abundant microbes in women with high stress versus low life stress, anxiety, depression, and PTSD, with the affected microbes mostly differing by symptom. Notably, members of phylum Proteobacteria were more abundant in women with high recent life stress and Spirochaetes was more abundant in women with high depression symptoms. Members of phylum Firmicutes were more abundant in the high trait anxiety and high depression groups. Genus Dialister (previously found to be lower in the gut of depressed non-pregnant people) was higher in women experiencing either high trait or state anxiety, or experiencing high depression symptoms, while genus Eikenella was elevated with high trait anxiety, depression or PTSD. CONCLUSIONS: The oral microbiome is associated with stress and mental health in pregnant women, in ways different from the gut microbiome or what has been found in non-pregnant people. CLINICAL IMPLICATIONS: Understanding oral microbiome-mental health relations may reveal future microbial targets to improve maternal psychological well-being.
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A biotin-free diet attenuates the incidence of collagen-induced arthritis and alleviates microbial dysbiosis.
Emerging evidence has shown that the gut microbiota and its products are important triggers in the pathogenesis of rheumatoid arthritis (RA). Biotin is a diet- and microbiome-dependent metabolite and an immune regulator; however, the role of biotin in RA remains unknown. In this study, we observed abnormal fecal biotin excretion in RA patients, which correlated with microbial alterations. Specifically, biotin content was inversely associated with gut microbial genera enriched in healthy controls, including Roseburia and Dorea. Meanwhile, it positively correlated with Oscillospira, which was highly enriched in RA individuals. Moreover, collagen-induced arthritis (CIA) mice fed a biotin-free diet had attenuated arthritis incidence with depressed differentiation of splenic CD3+ T cells and restored microbial diversities. The biotin-free diet also increased bone mass and protected against inflammation-induced bone loss in CIA mice. Additionally, the biotin-free diet reshaped the host metabolic phenotype of amino acids and microbial composition. Notably, biotin deficiency ameliorated the augmentation of Oscillospira in CIA mice. Collectively, our results suggested a potential link between biotin deficiency, gut microbiota dysbiosis and CIA progression.
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Therapeutic potential of faecal microbiota transplantation for alcohol use disorder, a narrative synthesis.
BACKGROUND: Faecal microbiota transplantation is proposed as an alternative therapy to treat alcohol use disorder and has completed a Phase 1 clinical trial, with a Phase 2 clinical trial underway. Alcohol, a modifiable risk factor for noncommunicable diseases, resulted in approximately 3 million global deaths (5 %) in 2016 according to the World Health Organization. AIMS: A narrative synthesis examines the effects of alcohol and faecal microbiota transplantation on gut microbiota and how gut microbiota impacts the gut-brain axis, leading to certain behavioural symptoms of alcohol use disorder. These behavioural symptoms are alcohol craving and relapse in humans; and preference for alcohol, anxiety and depression in rodents. SEARCH METHODS AND RESULTS: Electronic databases PubMed, Embase, and Scopus were searched in January 2024 using the terms: faecal microbiota trans* AND alcohol AND microbio*. Ten studies out of 964 met the inclusion criteria of published primary studies with faecal microbiota transplantation as an intervention to study the gut-brain axis in alcohol use disorder. RESULTS: The gut microbiota is altered in alcohol use disorder, which can be modified with faecal microbiota transplantation. Behavioural symptoms such as alcohol craving and relapse are associated with inflammation due to a loss of intestinal barrier function. Beneficial microbiota produce short-chain fatty acids that maintain intestinal barrier function and reduce inflammation. Studies also reported anxiety and depression-like behaviours, in addition to a preference for alcohol in alcohol-naïve rodents after faecal microbiota transplantation from patients with alcohol use disorder. CONCLUSIONS: Faecal microbiota transplantation may moderate the behavioural symptoms of alcohol use disorder by altering gut microbiota, affecting intestinal permeability and inflammation, however, specific gut microbiota composition and long-term treatment outcomes require further clinical studies.
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Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior.
Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of vehicle (dH2O) in nonobese diabetic (NOD) mice induced a social avoidance behavior that was not observed in C57BL/6 mice. This was not observed in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic analysis identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior.
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Feasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial.
OBJECTIVES: Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD. METHODS: The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial (n = 15) of enema-delivered FMT (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. RESULTS: Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD. CONCLUSIONS: All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.
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Longitudinal Influence of Prescribed Antidepressants on Fecal and Oral Microbiomes Among Veterans With Major Depressive Disorder.
OBJECTIVE: The purpose of this study was to evaluate the influence of a new course of antidepressant monotherapy on gut and oral microbiomes and the relationship to depressive symptoms. METHODS: Longitudinal microbiome samples obtained from 10 U.S. veterans were analyzed. Baseline samples were taken before a new course of antidepressant monotherapy (either switching from a previous treatment or starting a new treatment). Targeted genomic sequencing of the microbiome samples was used to analyze changes in taxonomy and diversity across participants, medications, and medication class. Associations between these changes and Patient Health Questionnaire-9 (PHQ-9) scores were analyzed. RESULTS: Taxonomic variability was observed across participants, with the individual being the main microbial community driver. In terms of the fecal microbiome, antidepressants were associated with shifts toward Bacteroides being less abundant and Blautia, Pseudomonas, or Faecalibacterium being more abundant. Likewise, the composition of the oral microbiome was variable, with individual participants being the primary drivers of community composition. In the oral samples, the relative abundance of Haemophilus decreased after antidepressants were started. Increases in Blautia and decreases in Bacteroides were associated with lower PHQ-9 scores. CONCLUSIONS: Antidepressants were found to influence fecal and oral microbiomes such that a new course of antidepressant monotherapy was associated with taxonomic alterations toward healthier states in both fecal and oral microbiomes, which were associated with decreases in depressive symptoms. Additional longitudinal research is required to increase understanding of microbiomes and symptom-based changes, with a particular focus on potential differences between medication classes and underlying mechanisms.
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Circadian rhythms, gut microbiota, and diet: Possible implications for health.
AIMS: Over the past years, interest in chrono-nutrition has grown enormously as the fundamental role of circadian rhythms in regulating most physiological and metabolic processes has become clearer. Recently, the influence of circadian rhythms on the gut microbiota (GM) composition has also emerged, as more than half of the total microbial composition fluctuates rhythmically throughout the day. At the same time, other studies have observed that the GM itself synchronises the host's circadian biological clock through signals of a different nature. Therefore, it has been hypothesised that there is a two-way communication between the circadian rhythms of the host and the GM, but researchers have only just begun to identify some of its action mechanisms. The manuscript aim is, therefore, to gather and combine the latest evidence in the field of chrono-nutrition with the more recent research on the GM, in order to investigate their relationship and their potential impact on human health. DATA SYNTHESIS: Considering current evidence, a desynchronization of circadian rhythms is closely associated with an alteration in the abundance and functionality of the gut microbiota with consequent deleterious effects on health, such as increased risk of numerous pathologies, including cardiovascular disease, cancer, irritable bowel disease, and depression. A key role in maintaining the balance between circadian rhythms and GM seems to be attributed to meal-timing and diet quality, as well as to certain microbial metabolites, in particular short-chain fatty acids. CONCLUSIONS: Future studies are needed to decipher the link between the circadian rhythms and specific microbial patterns in relation to different disease frameworks.
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Extracellular Vesicles from Gram-positive and Gram-negative Probiotics Remediate Stress-Induced Depressive Behavior in Mice.
Chronic stress causes maladaptive changes in the brain that lead to depressive behavior. In the present study, we investigate whether chronic stress alters gut microbiota compositions that are related to stress-induced maladaptive changes in the brain. Mice treated with daily 2-h restraint for 14 days (CRST) exhibit depressive-like behavior. Sequence readings of 16S rRNA genes prepared from fecal samples taken from CRST-treated mice suggest that chronic stress induces gut microbiota changes that are pronounced in the post-stress period, relative to those that occur in the 14-day stress phase. The genus Lactobacillus is one such microbiota substantially changed following chronic stress. In contrast, intraperitoneal injection of extracellular vesicles (EVs) isolated from culture media of the Gram-positive probiotic Lactobacillus plantarum is sufficient to ameliorate stress-induced depressive-like behavior. Interestingly, EVs from the Gram-positive probiotic Bacillus subtilis and EVs from the Gram-negative probiotic Akkermansia muciniphila also produce anti-depressive-like effects. While chronic stress decreases the expression of MeCP2, Sirt1, and/or neurotrophic factors in the hippocampus, EVs from the three selected probiotics differentially restore stress-induced changes of these factors. These results suggest that chronic stress produces persistent changes in gut microbiota composition, whereas purified EVs of certain probiotics can be used for treatment of stress-induced depressive-like behavior.
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Design of functional glucomannan via acetylation for targeting regulation of gut microbiota.
In this study, konjac glucomannan (KGM) was acetylated, followed by the investigation of its corresponding structural and physicochemical properties. Spectroscopic analyses, including FTIR and NMR, confirmed the introduction of acetyl groups. Rheological measurements found a decrease in both viscosity and gel strength of the acetylated KGM (AKGM), attributing to weaker intermolecular interactions. The current study also revealed that the acetylation of KGM led to reduced gut microbiota fermentation kinetics, followed by a lower short-chain fatty acids (SCFAs) generation, which may be due to the stearic hindrance raised from the introduction of acetyl groups onto its macromolecules. Interesting, although both two types of polysaccharides (before and after acetylation) improved gut microbiota profile in term of enriched probiotics profile, AKGM even generated a lower ratio of Firmicutes/Bacteroidota compared to that of KGM, which was negatively correlated with the degree of acetylation of KGM. Importantly, this was the first time to reveal that Prevotella_9 was selectively promoted in AKGM, followed by a greatly depressed growth of pathogens, such as Escherichia-Shigella compared to KGM. Nevertheless, this study demonstrated that the change in the molecular structure of the polysaccharides targets the promotion of specific bacteria, which may highlight their potent application for individual healthy intervention.