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Differential Effects of Two Common Antiparasitics on Microbiota Resilience.
BACKGROUND: Parasitic infections challenge vertebrate health worldwide, and off-target effects of antiparasitic treatments may be an additional obstacle to recovery. However, there have been few investigations of the effects of antiparasitics on the gut microbiome in the absence of parasites. METHODS: We investigated whether two common antiparasitics-albendazole (ALB) and metronidazole (MTZ)-significantly alter the gut microbiome of parasite-free mice. We treated mice with ALB or MTZ daily for 7 days and sampled the fecal microbiota immediately before and after treatment and again after a two-week recovery period. RESULTS: ALB did not immediately change the gut microbiota, while MTZ decreased microbial richness by 8.5% and significantly changed community structure during treatment. The structural changes caused by MTZ included depletion of the beneficial family Lachnospiraceae, and predictive metagenomic analysis revealed that these losses likely depressed microbiome metabolic function. Separately, we compared the fecal microbiotas of treatment groups after recovery, and there were minor differences in community structure between the ALB, MTZ, and sham-treated control groups. CONCLUSIONS: These results suggest that a healthy microbiome is resilient after MTZ-induced depletions of beneficial gut microbes, and ALB may cause slight, latent shifts in the microbiota but does not deplete healthy gut microbiota diversity.
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Do common antibiotic treatments influence emotional processing?
Antibiotics are among the most commonly prescribed medications worldwide, yet research in recent years has revealed the detrimental effect they can have on the human microbiome, with implications for health. The community of microorganisms inhabiting the gut has been shown to regulate physiological and neural processes. Since studies in both humans and animal models have revealed that the gut microbiome can affect the brain, influencing emotion and cognition, here we investigate whether antibiotic treatment is associated with changes in emotional processing and mood with a between-subject design in 105 young healthy adult volunteers, using both psychological tests and questionnaires. As both the immune system and vagal signalling can mediate the microbiome-gut-brain axis, we also assess whether there is any evidence of such changes in participant physiology. We find that individuals who have taken antibiotics in the past three months show a stronger emotional bias towards sadness and at a physiological level they have a higher heart rate (though this does not mediate the relationship with negative bias). While we cannot rule out a possible role of prior infection, our findings are in any case highly relevant in light of research revealing that antibiotics are linked to increased susceptibility to depression and anxiety. Our results also have implications for listing antibiotic use as an exclusion criterion in studies on emotional processing and psychophysiology.
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Gut microbiota remodeling and sensory-emotional functional disruption in adolescents with bipolar depression.
BACKGROUND: Adolescence is the peak period of newly-onset bipolar disorder (BD). Accumulating studies have revealed disturbed gut microbiota can interfere with neurodevelopment in adolescents. In this study, we aimed to characterize the gut microbiota in adolescents with BD and its correlation with brain dysfunction. METHODS: Thirty unmedicated BD adolescents within depressive episode were recruited and underwent four-week quetiapine treatment. Twenty-five age-, gender-, and BMI-matched healthy controls (HCs) were recruited. Fecal samples were collected from HCs and all BD adolescents before and after treatment and analyzed by metagenomic sequencing. Resting-state cranial functional magnetic images were collected from 21 BD adolescents before treatment. Random forest models were used to evaluate the discriminative power of gut microbiota and neuroimaging data for BD and the predictive power of treatment effect. RESULTS: Although no significant difference was found in alpha-diversity, intra- and inter-group differences in beta-diversity were observed among HCs, pre- and post-treatment patients. Compared to HCs, unmedicated BD adolescents presented a differentiated gut microbial communities, which correlated to the short-chain fatty acids, choline, lipids, vitamins, polyamines, aromatic amino acids metabolic pathways. Four-week quetiapine treatment improved the abundance of specific genus, such as Odoribacter splanchnicus, Oribacterium sinus, Hafnia alvei, Fusobacterium periodonticum, Acidaminococcus interstini and Veillonella rogosae. Neuroimaging analysis revealed sensor-emotional brain regions were associated with BD severity. Finally, random forest models based on gut microbial biomarkers can well distinguish unmedicated BD from HCs (AUC = 91.12%) and predict the treatment effect (AUC = 91.84%). The random forest model integrating gut microbiota and neuroimaging data exhibited a better predictive efficacy than using microbiota data alone. CONCLUSION: This study first characterized the gut microbiota architecture in adolescent BD. Combining gut microbiota and brain function biomarkers may benefit disease diagnosis and predict treatment outcome. Nonetheless, these findings should be carefully interpreted considering the limitations of a modest sample size and the absence of detailed mechanistic explorations. Trial registration NCT05480150. Registered 29 July 2022-Retrospectively registered, https://clinicaltrials.gov/study/NCT05480150 .
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Production of Psychoactive Metabolites by Gut Bacteria.
The gut microbiome plays a vital role in numerous aspects of physiology, including functions related to metabolism, the immune system, behaviour, brain structure and function. Furthermore, it is now becoming increasingly clear that alterations in microbial composition or diversity are implicated in several disease states, including anxiety, depression, autism spectrum disorder (ASD), Alzheimer's disease (AD), Parkinson's disease (PD), obesity, and diabetes. Therefore, therapeutic targeting of the gut microbiota has the potential to be useful in the treatment of both stress-related disorders and metabolic diseases. An important method by which the gut microbiome can influence the gut-brain axis is through microbial production of psychoactive metabolites. Several bacteria have been shown to produce metabolites which can impact host health, such as short-chain fatty acids, conjugated linoleic acid, antimicrobials, exopolysaccharides, and vitamins. Furthermore, several molecules with neuroactive functions, including serotonin, gamma-aminobutyric acid, catecholamines, and acetylcholine, have been isolated from bacteria within the human gut. This review aims to explore the psychoactive metabolites reported to be produced by gut bacteria, particularly those of relevance to stress-related disorders. Screening methods for psychoactive metabolite production, as well as the challenges and limitations of this research, will also be addressed. Finally, the implications of metabolite production for neuropsychiatric disorders such as depression, anxiety, and stress, behavioural disorders such as ASD, and neurodegenerative disorders such as AD and PD will be discussed.
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Food matters: how the microbiome and gut-brain interaction might impact the development and course of anorexia nervosa.
Anorexia nervosa (AN) is one of the most common chronic illnesses in female adolescents and exhibits the highest mortality risk of all psychiatric disorders. Evidence for the effectiveness of psychotherapeutic or psychopharmacological interventions is weak. Mounting data indicate that the gut microbiome interacts with the central nervous system and the immune system by neuroendocrine, neurotransmitter, neurotrophic and neuroinflammatory afferent and efferent pathways. There is growing evidence that the gut microbiota influences weight regulation and psychopathology, such as anxiety and depression. This article reviews how the gut-brain interaction may impact the development and course of AN. A "leaky gut", characterized by antigens traversing the intestinal wall, was demonstrated in an animal model of AN, and could underlie the low-grade inflammation and increased risk of autoimmune diseases found in AN. Moreover, starvation has a substantial impact on the gut microbiome, and diets used for re-nutrition based on animal products may support the growth of bacteria capable of triggering inflammation. As there is currently no empirically derived agreement on therapeutic re-nourishment in AN, this review discusses how consideration of gut-brain interactions may be important for treatment regarding the determination of target weight, rapidity of weight gain, refeeding methods and composition of the diet which might all be of importance to improve long-term outcome of one of the most chronic psychiatric disorders of adolescence.
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Probiotic Supplementation Improves Cognitive Function and Mood with Changes in Gut Microbiota in Community-Dwelling Older Adults: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.
Probiotics have been proposed to ameliorate cognitive impairment and depressive disorder via the gut-brain axis in patients and experimental animal models. However, the beneficial role of probiotics in brain functions of healthy older adults remains unclear. Therefore, a randomized, double-blind, and placebo-controlled multicenter trial was conducted to determine the effects of probiotics on cognition and mood in community-dwelling older adults. Sixty-three healthy elders (≥65 years) consumed either placebo or probiotics containing Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI for 12 weeks. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Brain functions were measured using the Consortium to Establish a Registry for Alzheimer's disease, Satisfaction with life scale, stress questionnaire, Geriatric depression scale, and Positive affect and negative affect schedule. Blood brain-derived neurotrophic factor (BDNF) was determined using enzyme-linked immunosorbent assay. Relative abundance of inflammation-causing gut bacteria was significantly reduced at Week 12 in the probiotics group (p < .05). The probiotics group showed greater improvement in mental flexibility test and stress score than the placebo group (p < .05). Contrary to placebo, probiotics significantly increased serum BDNF level (p < .05). Notably, the gut microbes significantly shifted by probiotics (Eubacterium and Clostridiales) showed significant negative correlation with serum BDNF level only in the probiotics group (RS = -0.37, RS = -0.39, p < .05). In conclusion, probiotics promote mental flexibility and alleviate stress in healthy older adults, along with causing changes in gut microbiota. These results provide evidence supporting health-promoting properties of probiotics as a part of healthy diet in the older adults.
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Gut microbiome-brain-cirrhosis axis.
Cirrhosis is characterized by inflammation, degeneration, and fibrosis of liver tissue. Along with being the most common cause of liver failure and liver transplant, cirrhosis is a significant risk factor for several neuropsychiatric conditions. The most common of these is HE, which is characterized by cognitive and ataxic symptoms, resulting from the buildup of metabolic toxins with liver failure. However, cirrhosis patients also show a significantly increased risk for neurodegenerative diseases such as Alzheimer and Parkinson diseases, and for mood disorders such as anxiety and depression. In recent years, more attention has been played to communication between the ways the gut and liver communicate with each other and with the central nervous system, and the way these organs influence each other's function. This bidirectional communication has come to be known as the gut-liver-brain axis. The gut microbiome has emerged as a key mechanism affecting gut-liver, gut-brain, and brain-liver communication. Clinical studies and animal models have demonstrated the significant patterns of gut dysbiosis when cirrhosis is present, both with or without concomitant alcohol use disorder, and have provided compelling evidence that this dysbiosis also influences the cognitive and mood-related behaviors. In this review, we have summarized the pathophysiological and cognitive effects associated with cirrhosis, links to cirrhosis-associated disruption of the gut microbiome, and the current evidence from clinical and preclinical studies for the modulation of the gut microbiome as a treatment for cirrhosis and associated neuropsychiatric conditions.
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Sex-specific modulation of the gut microbiome and behavior in Siberian hamsters.
The gut microbiome is a diverse, host-specific, and symbiotic bacterial environment that is critical for mammalian survival and exerts a surprising yet powerful influence on brain and behavior. Gut dysbiosis has been linked to a wide range of physical and psychological disorders, including autism spectrum disorders and anxiety, as well as autoimmune and inflammatory disorders. A wealth of information on the effects of dysbiosis on anxiety and depression has been reported in laboratory model systems (e.g., germ-free mice); however, the effects of microbiome disruption on social behaviors (e.g., aggression) of non-model species that may be particularly important in understanding many aspects of physiology and behavior have yet to be fully explored. Here we assessed the sex-specific effects of a broad-spectrum antibiotic on the gut microbiome and its effects on social behaviors in male and female Siberian hamsters (Phodopus sungorus). In Experiment 1, we administered a broad-spectrum antibiotic on a short-term basis and found that antibiotic treatment altered the microbial communities in the gut in male and female hamsters. In Experiment 2, we tested the effects of single versus repeated antibiotic treatment (including a recovery phase) on behavior, and found that two, but not one, treatments caused marked decreases in aggressive behavior, but not other social behaviors, in males; aggression returned to normal levels following recovery. Antibiotic-treated females, in contrast, showed decreased aggression after a single treatment, with all other social behaviors unaffected. Unlike males, female aggression did not return to normal during either recovery period. The present findings demonstrate that modest antibiotic treatment results in marked disruption of the gut microbiome in hamsters, akin to research done in other rodent species and humans. Further, we show that treatment with a broad-spectrum antibiotic, which has dysbiotic effects, also has robust, sex-specific effects on aggression, a critical behavior in the survival and reproductive success of many rodent species.
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Gut microbes in neurocognitive and mental health disorders.
INTRODUCTION: As individuals age, the prevalence of neurocognitive and mental health disorders increases. Current biomedical treatments do not completely address the management of these conditions. Despite new pharmacological therapy the challenges of managing these diseases remain.There is increasing evidence that the Gut Microbiome (GM) and microbial dysbiosis contribute to some of the more prevalent mental health and neurocognitive disorders, such as depression, anxiety, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), schizophrenia, bipolar disorder (BP), and dementia as well as the behavioural and psychological symptoms of dementia (BPSD) through the microbiota-gut-brain axis. Methodology: Scoping review about the effect of gut microbiota on neurocognitive and mental health disorders. RESULTS: This scoping review found there is an evolving evidence of the involvement of the gut microbiota in the pathophysiology of neurocognitive and mental health disorders. This manuscript also discusses how the psychotropics used to treat these conditions may have an antimicrobial effect on GM, and the potential for new strategies of management with probiotics and faecal transplantation. CONCLUSIONS: This understanding can open up the need for a gut related approach in these disorders as well as unlock the door for the role of gut related microbiota management. KEY MESSAGES Challenges of managing mental health conditions remain in spite of new pharmacological therapy. Gut dysbiosis is seen in various mental health conditions. Various psychotropic medications can have an influence on the gut microbiota by their antimicrobial effect.
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The many faces of microbiota-gut-brain axis in autism spectrum disorder.
The gut-brain axis is gaining more attention in neurodevelopmental disorders, especially autism spectrum disorder (ASD). Many factors can influence microbiota in early life, including host genetics and perinatal events (infections, mode of birth/delivery, medications, nutritional supply, and environmental stressors). The gut microbiome can influence blood-brain barrier (BBB) permeability, drug bioavailability, and social behaviors. Developing microbiota-based interventions such as probiotics, gastrointestinal (GI) microbiota transplantation, or metabolite supplementation may offer an exciting approach to treating ASD. This review highlights that RNA sequencing, metabolomics, and transcriptomics data are needed to understand how microbial modulators can influence ASD pathophysiology. Due to the substantial clinical heterogeneity of ASD, medical caretakers may be unlikely to develop a broad and effective general gut microbiota modulator. However, dietary modulation followed by administration of microbiota modulators is a promising option for treating ASD-related behavioral and gastrointestinal symptoms. Future work should focus on the accuracy of biomarker tests and developing specific psychobiotic agents tailored towards the gut microbiota seen in ASD patients, which may include developing individualized treatment options.