Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota-gut-brain ...crosstalk. However, the pathways through which SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, research directly exploring the role of SCFAs as potential mediators of the effects of microbiota-targeted interventions on affective and cognitive functioning is sparse, especially in humans. This Review summarizes existing knowledge on the potential of SCFAs to directly or indirectly mediate microbiota-gut-brain interactions. The effects of SCFAs on cellular systems and their interaction with gut-brain signalling pathways including immune, endocrine, neural and humoral routes are described. The effects of microbiota-targeted interventions such as prebiotics, probiotics and diet on psychological functioning and the putative mediating role of SCFA signalling will also be discussed, as well as the relationship between SCFAs and psychobiological processes. Finally, future directions to facilitate direct investigation of the effect of SCFAs on psychological functioning are outlined.
We provide a general framework for understanding functional gastrointestinal disorders (FGIDs) from a biopsychosocial perspective. More specifically, we provide an overview of the recent research on ...how the complex interactions of environmental, psychological, and biological factors contribute to the development and maintenance of FGIDs. We emphasize that considering and addressing all these factors is a conditio sine qua non for appropriate treatment of these conditions. First, we provide an overview of what is currently known about how each of these factors—the environment, including the influence of those in an individual’s family, the individual’s own psychological states and traits, and the individual’s (neuro)physiological make-up—interact to ultimately result in the generation of FGID symptoms. Second, we provide an overview of commonly used assessment tools that can assist clinicians in obtaining a more comprehensive assessment of these factors in their patients. Finally, the broader perspective outlined earlier is applied to provide an overview of centrally acting treatment strategies, both psychological and pharmacological, which have been shown to be efficacious to treat FGIDs.
In this Review, after a brief historical introduction, we first provide an overview of epidemiological studies that demonstrate an association between functional dyspepsia and psychological traits, ...states or psychiatric disorders. These studies suggest an important intrinsic role for psychosocial factors and psychiatric disorders, especially anxiety and depression, in the aetiopathogenesis of functional dyspepsia, in addition to their putative influence on health-care-seeking behaviour. Second, we describe pathophysiological evidence on how psychosocial factors and psychiatric disorders might exert their role in functional dyspepsia. Novel insights from functional brain imaging studies regarding the integration of gut-brain signals, processed in homeostatic-interoceptive brain regions, with input from the exteroceptive system, the reward system and affective and cognitive circuits, help to clarify the important role of psychological processes and psychiatric morbidity. We therefore propose an integrated model of functional dyspepsia as a disorder of gut-brain signalling, supporting a biopsychosocial approach to the diagnosis and management of this disorder.
Over the past few years, scientific interest in the gut–brain axis (i.e., the bidirectional communication system between the gastrointestinal tract and the brain) has exploded, mostly due to the ...identification of the gut microbiota as a novel key player in this communication. However, important progress has also been made in other aspects of gut–brain axis research, which has been relatively underemphasized in the review literature. Therefore, in this review, we provide a comprehensive, although not exhaustive, overview of recent research on the functional neuroanatomy of the gut–brain axis and its relevance toward the multidisciplinary field of health neuroscience, excluding studies on the role of the gut microbiota. More specifically, we first focus on irritable bowel syndrome, after which we outline recent findings on the role of the gut–brain axis in appetite and feeding regulation, primarily focusing on the impact of subliminal nutrient‐related gut–brain signals. We conclude by providing future perspectives to facilitate translation of the findings from gut–brain axis neuroscientific research to clinical applications in these domains.
This review provides a comprehensive overview of recent research on the functional neuroanatomy of the gut–brain axis (i.e., the bidirectional communication system between the gastrointestinal tract and the brain) and its relevance toward the multidisciplinary field of health neuroscience, excluding studies on the role of the gut microbiota. It focuses on irritable bowel syndrome and the role of the gut–brain axis in appetite and feeding regulation.
The relationship between gut microbial metabolism and mental health is one of the most intriguing and controversial topics in microbiome research. Bidirectional microbiota-gut-brain communication has ...mostly been explored in animal models, with human research lagging behind. Large-scale metagenomics studies could facilitate the translational process, but their interpretation is hampered by a lack of dedicated reference databases and tools to study the microbial neuroactive potential. Surveying a large microbiome population cohort (Flemish Gut Flora Project, n = 1,054) with validation in independent data sets (n
= 1,070), we studied how microbiome features correlate with host quality of life and depression. Butyrate-producing Faecalibacterium and Coprococcus bacteria were consistently associated with higher quality of life indicators. Together with Dialister, Coprococcus spp. were also depleted in depression, even after correcting for the confounding effects of antidepressants. Using a module-based analytical framework, we assembled a catalogue of neuroactive potential of sequenced gut prokaryotes. Gut-brain module analysis of faecal metagenomes identified the microbial synthesis potential of the dopamine metabolite 3,4-dihydroxyphenylacetic acid as correlating positively with mental quality of life and indicated a potential role of microbial γ-aminobutyric acid production in depression. Our results provide population-scale evidence for microbiome links to mental health, while emphasizing confounder importance.
Short-chain fatty acids (SCFAs) are products of microbial fermentation of dietary fiber in the colon and may mediate microbiota-gut-brain communication. However, their role in modulating ...psychobiological processes that underlie the development of stress- and anxiety-related disorders is not mechanistically studied in humans. In this triple-blind, randomized, placebo-controlled intervention trial, we examine in a parallel group design the effects of 1-week colonic SCFA-mixture delivery in doses equivalent to fermentation of 10 g or 20 g of arabinoxylan oligosaccharides on responses to psychosocial stress and fear tasks in 66 healthy men. We demonstrate that low and high doses of SCFAs significantly attenuate the cortisol response to psychosocial stress compared to placebo. Both doses of SCFAs increase serum SCFA levels and this increase in circulating SCFAs co-varies significantly with the attenuation of the cortisol response to psychosocial stress. Colonic SCFA delivery does not modulate fecal SCFA concentrations, serum brain-derived neurotrophic factor, cortisol awakening response, fear learning and extinction, or subjective mood ratings. These results demonstrate that colon-delivered SCFAs modulate hypothalamic-pituitary-adrenal axis reactivity to psychosocial stress, thereby supporting their hypothesized role in microbiota-gut-brain communication.
Experimental research evaluating differences between the visceral and somatic stimulation is limited to pain and typically uses different induction methods for visceral and somatic stimulation (e.g., ...rectal balloon distention vs. tactile hand stimulation). Our study aimed to compare differences in response time, intensity, unpleasantness, and threat between identical electrical visceral and somatic stimulations at both painful and non-painful perceptual thresholds.
Electrical stimulation was applied to the wrist and distal esophagus in 20 healthy participants. A double pseudorandom staircase determined perceptual thresholds of Sensation, Discomfort, and Pain for the somatic and visceral stimulations, separately. Stimulus reaction time (ms, via button press), and intensity, unpleasantness, and threat ratings were recorded after each stimulus. General linear mixed models compared differences in the four outcomes by stimulation type, threshold, and the stimulation type-by-threshold interaction. Sigmoidal maximum effect models evaluated differences in outcomes across all delivered stimulation intensities.
Overall, visceral stimulations were perceived as more intense, threatening, and unpleasant compared to somatic stimulations, but participants responded faster to somatic stimulations. There was no significant interaction effect, but planned contrasts demonstrated differences at individual thresholds. Across all delivered intensities, higher intensity stimulations were needed to reach the half-maximum effect of self-reported intensity, unpleasantness, and threat ratings in the visceral domain.
Differences exist between modalities for both non-painful and painful sensations. These findings may have implications for translating paradigms and behavioral treatments from the somatic domain to the visceral domain, though future research in larger clinical samples is needed.
Summary
Background
Functional dyspepsia, consisting of epigastric pain syndrome and postprandial distress syndrome, is a prevalent functional gastrointestinal disorder. To date, only limited ...treatment options are available and conflicting results in terms of efficacy have been reported. Consequently, nonpharmacological treatment options are increasingly being explored for functional dyspepsia.
Aim
To provide an overview of current pharmacological and nonpharmacological treatment options for functional dyspepsia.
Methods
A literature search was conducted on Pubmed and other sources to identify relevant studies.
Results
Acid suppressive therapy reduced symptoms in 30%‐70% of the patients, with higher benefit in epigastric pain syndrome and superior effectiveness for proton pump inhibitors compared to H2‐antagonists. Prokinetic agents, primarily used to treat postprandial distress syndrome, showed variable efficiency: 59%‐81% responder rate for dopamine receptor antagonists, 32%‐91% for serotonin‐4‐receptor agonists and 31%‐80% for muscarinic receptor antagonists. H Pylori eradication, recommended in infected patients, was effective in 24%‐82%. Refractory symptoms are addressed with neuromodulators. However, their efficacy in functional dyspepsia remains incompletely elucidated, available data showing symptom reduction in 27%‐71% of the patients. Regarding herbal agents, peppermint oil reduced symptoms in 66%‐91%, rikkunshito in 29%‐34% and iberogast in 20%‐95%. Lastly, acupuncture, cognitive behavioural therapy and hypnotherapy may help to provide symptom control, but research on their efficacy remains sparse.
Conclusions
None of the available therapies is effective in the majority of patients without being associated with major side effects. Developing new treatment options is challenging due to the heterogeneity of functional dyspepsia, the lack of readily identified target mechanisms and the poor association between pathophysiological disturbances and symptoms.
LINKED CONTENTThis article is linked to Targher and Lippi and Mullish et al papers. To view these articles visit https://doi.org/10.1111/apt.15208 and https://doi.org/10.1111/apt.15215.
Sleep quality may affect symptom experience in irritable bowel syndrome (IBS). Our aim was to investigate the relationship between sleep quality and gastrointestinal (GI) symptoms using actigraphy ...and the experience sampling method.
Patients with IBS were recruited from a tertiary Neurogastroenterology clinic and the community. GI symptoms and mood were recorded on a smartphone application, 10 times per day, over 7 consecutive days. Subjective sleep quality was recorded every morning to reflect the night before. Objective measures of sleep quality were estimated from wrist-worn actigraphy. Cross-lagged structural equation models were built to assess the directionality of sleep-symptom relationships over time.
Eighty patients with IBS completed the study (mean age: 37 years range 20-68, 89% female, 78% community). Approximately 66% had a Pittsburgh Sleep Quality Index score ≥ 8, indicating a clinically significant sleep disturbance. Approximately 82% (95% CI: 72-90) screened positive for a sleep disorder, most commonly insomnia. In cross-lagged analysis, poor subjective sleep quality predicted next-day abdominal pain (0.036 < P < 0.040) and lower GI symptoms (0.030 < P < 0.032), but not vice versa. No significant relationship with GI symptoms was found for any objective sleep measure using actigraphy.
Poor subjective sleep quality was associated with higher next-day lower GI symptom levels, but not vice versa. Objective sleep measures did not predict next-day abdominal symptoms, potentially supporting the conclusion that it is the perception of sleep quality that is most influential. This study may be used to guide future research into the effect of sleep interventions on GI symptoms.
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