The host–intestinal microbiome interaction has gained much scientific attention in the past two decades, boosted by advances in DNA sequencing and cultivation techniques. An accumulating amount of evidence shows that gut microbes play crucial roles in gut homeostasis, immune system education, and are associated with quality-of-life indicators. Beneficial health factors are associated with the digestion of dietary fibres in the colon and the subsequent production of short-chain fatty acids, including acetate, propionate, and butyrate. Coprococcus is a butyrate-producing genus in the phylum Firmicutes, and its abundance is inversely correlated with several neuropsychological and neurodegenerative disorders. Case–control studies provide strong evidence of decreased abundance of Coprococcus spp. in depressed individuals. The species Coprococcus eutactus has the unique capacity to use two separate pathways for butyrate synthesis and has been found to be depleted in children with delayed language development and adults with Parkinson’s disease. The combined literature on Coprococcus and the gut microbiota–brain axis points towards enhanced butyrate production and reduced colonisation of pathogenic clades as factors explaining its association with health effects. The genus Coprococcus is a promising candidate for a mental health biomarker and an interesting lead for novel dietary-based preventive therapies for specific neurological disorders.

The evolution of the understanding of the intestinal microbiota and its influence on our organism leverages it as a potential protagonist in therapies aimed at diseases that affect not only the intestine but also neural pathways and the central nervous system itself. This study, developed from a thorough systematic review, sought to demonstrate the influence of the intervention on the intestinal microbiota in subjects with Alzheimer’s disease. Clinical trials using different classes of probiotics have depicted noteworthy remission of symptoms, whose measurement was performed based on screenings and scores applied before, during, and after the period of probiotics use, allowing the observation of changes in functionality and symptomatology of patients. On the other hand, faecal microbiota transplantation requires further validation through clinical trials, even though it has already been reported in case studies as promising from the symptomatology point of view. The current compilation of studies made it possible to demonstrate the potential influence of the intestinal microbiota on Alzheimer’s pathology. However, new clinical studies with a larger number of participants are needed to obtain further clarification on pathophysiological correlations.

Environmental stressors can disrupt the gut–brain relationship and alter the gut microbial composition, potentially leading to chronic pain, including neuropathic pain (NP). To understand this complex relationship, we conducted a systematic scoping review to examine the gut microbial-neuroimmune connection to NP and the potential therapeutic targets. The review includes English-language manuscripts in databases such as MEDLINE, Cochrane, and DOAJ between January 2000 and April 2022. Out of the 48 full texts examined, only 15 articles met the inclusion criteria. These included a randomised controlled trial involving 327 individuals, an in vitro, and 13 animal model studies. The findings suggest that the gut flora plays a role in the immunological, neurological, and metabolic signalling pathways associated with NP. Animal studies have been the primary focus in this area, indicating that an imbalanced-gut microbiome and subsequent activation of biochemical and neuro-immunologic pathways may influence the development of NP. This review provides a comprehensive summary of the gut microbiome-immune-NP axis and identifies potential therapeutic targets. However, since most of the evidence comes from animal studies, future research should include clinical trials to gain a better understanding of the role of gut microbiota in NP and discover new therapeutic strategies.

The first publication demonstrating that major depressive disorder (MDD) is associated with alterations in the gut microbiota appeared in 2008 (Maes et al., 2008). The purpose of the present study is to delineate a) the microbiome signature of the phenome of depression, including suicidal behaviours (SB) and cognitive deficits; the effects of adverse childhood experiences (ACEs) and recurrence of illness index (ROI) on the microbiome; and the microbiome signature of lowered high-density lipoprotein cholesterol (HDLc). We determined isometric log-ratio abundances or prevalences of gut microbiome phyla, genera, and species by analysing stool samples from 37 healthy Thai controls and 32 MDD patients using 16S rDNA sequencing. Six microbiome taxa accounted for 36% of the variance in the depression phenome, namely Hungatella and Fusicatenibacter (positive associations) and Butyricicoccus, Clostridium, Parabacteroides merdae, and Desulfovibrio piger (inverse association). This profile (labelled enterotype 1) indicates compositional dysbiosis, is strongly predicted by ACE and ROI, and is linked to SB. A second enterotype was developed that predicted a decrease in HDLc and an increase in the atherogenic index of plasma (Bifidobacterium, P. merdae, and Romboutsia were positively associated, while Proteobacteria and Clostridium sensu stricto were negatively associated). Together, enterotypes 1 and 2 explained 40.4% of the variance in the depression phenome, and enterotype 1 in conjunction with HDLc explained 39.9% of the variance in current SB. In conclusion, the microimmuneoxysome is a potential new drug target for the treatment of severe depression and SB and possibly for the prevention of future episodes.

Perturbations to the gut microbiome are implicated in altered neurodevelopmental trajectories that may shape life span risk for emotion dysregulation and affective disorders. However, the sensitive periods during which the microbiome may influence neurodevelopment remain understudied. We investigated relationships between gut microbiome composition across infancy and temperament at 12 months of age. In 67 infants, we examined if gut microbiome composition assessed at 1–3 weeks, 2, 6, and 12 months of age was associated with temperament at age 12 months. Stool samples were sequenced using the 16S Illumina MiSeq platform. Temperament was assessed using the Infant Behavior Questionnaire-Revised (IBQ-R). Beta diversity at age 1–3 weeks was associated with surgency/extraversion at age 12 months. Bifidobacterium and Lachnospiraceae abundance at 1–3 weeks of age was positively associated with surgency/extraversion at age 12 months. Klebsiella abundance at 1–3 weeks was negatively associated with surgency/extraversion at 12 months. Concurrent composition was associated with negative affectivity at 12 months, including a positive association with Ruminococcus-1 and a negative association with Lactobacillus. Our findings support a relationship between gut microbiome composition and infant temperament. While exploratory due to the small sample size, these results point to early and late infancy as sensitive periods during which the gut microbiome may exert effects on neurodevelopment.

High-protein meals and foods are promoted for their beneficial effects on satiety, weight loss and glucose homeostasis. However, the mechanisms involved and the long-term benefits of such diets are still debated. We here review how the characterisation of intestinal gluconeogenesis (IGN) sheds new light on the mechanisms by which protein diets exert their beneficial effects on health. The small intestine is the third organ (in addition to the liver and kidney) contributing to endogenous glucose production via gluconeogenesis. The particularity of glucose produced by the intestine is that it is detected in the portal vein and initiates a nervous signal to the hypothalamic nuclei regulating energy homeostasis. In this context, we demonstrated that protein diets initiate their satiety effects indirectly via IGN and portal glucose sensing. This induction results in the activation of brain areas involved in the regulation of food intake. The μ-opioid-antagonistic properties of protein digests, exerted in the portal vein, are a key link between IGN induction and protein-enriched diet in the control of satiety. From our results, IGN can be proposed as a mandatory link between nutrient sensing and the regulation of whole-body homeostasis. The use of specific mouse models targeting IGN should allow us to identify several metabolic functions that could be controlled by protein diets. This will lead to the characterisation of the mechanisms by which protein diets improve whole-body homeostasis. These data could be the basis of novel nutritional strategies targeting the serious metabolic consequences of both obesity and diabetes.

Infant colic is a condition of unknown cause which can result in carer distress and attachment difficulties. Recent studies have implicated the gut microbiota in infant colic, and certain probiotics have demonstrated possible efficacy. We aim to investigate whether the intestinal microbiota composition in infants with colic is associated with cry/fuss time at baseline, persistence of cry/fuss at 4-week follow-up, or child behavior at 2 years of age. Fecal samples from infants with colic (n = 118, 53% male) were analyzed using 16S rRNA sequencing. After examining the alpha and beta diversity of the clinical samples, we performed a differential abundance analysis of the 16S data to look for taxa that associate with baseline and future behavior, while adjusting for potential confounding variables. In addition, we used random forest classifiers to evaluate how well baseline gut microbiota can predict future crying time. Alpha diversity of the fecal microbiota was strongly influenced by birth mode, feed type, and child gender, but did not significantly associate with crying or behavioral outcomes. Several taxa within the microbiota (including Bifidobacterium, Clostridium, Lactobacillus, and Klebsiella) associate with colic severity, and the baseline microbiota composition can predict further crying at 4 weeks with up to 65% accuracy. The combination of machine learning findings with associative relationships demonstrates the potential prognostic utility of the infant fecal microbiota in predicting subsequent infant crying problems.

Background. Previous studies have shown a potential for cannabis in disorders of the digestive organs. We aimed to investigate whether cannabis use disorders (CUD) would decrease the risk of incident disorders of the digestive organs, in people with schizophrenia and population controls.

Methods. We combined nationwide Danish registers to identify 21 066 cases with schizophrenia and 176 935 sex-and-age-matched controls. Two models were analyzed for the associations between CUD and digestive disorders in time-varying Cox regressions: one adjusted for sex, year of birth, and calendar year; and one further adjusted for alcohol and other substance use disorders and parental education.

Results. CUD was associated with a decreased risk of developing disorders of gut–brain interaction (e.g. irritable bowel syndrome, dyspepsia, etc.) among cases with schizophrenia (HR = 0.84, 95% CI 0.74–0.94, p = 0.003). CUD was associated with decreased risk of inflammatory bowel disease (HR = 0.70, 95% CI 0.49–0.99, p = 0.045) in the basically adjusted model, dropping just below statistical significance in the fully adjusted model (HR = 0.71, 95% CI 0.48–1.03, p = 0.07). CUD displayed a tendency toward a decreased risk of serious disorders of the digestive organs among cases with schizophrenia (HR = 0.89, 95% CI 0.77–1.02, p = 0.09) in the fully adjusted model. No associations were observed among controls.

Conclusions. In people with schizophrenia, but not in controls, CUD is associated with decreased risk of disorders of gut–brain interaction and inflammatory bowel disease, and possibly other serious disorders of the digestive organs. Our findings could lead to new targets for treatment and prevention of disorders of the digestive organs.

A healthy gut microbiota plays many crucial functions in the host, being involved in the correct development and functioning of the immune system, assisting in the digestion of certain foods and in the production of health-beneficial bioactive metabolites or ‘pharmabiotics’. These include bioactive lipids (including SCFA and conjugated linoleic acid) antimicrobials and exopolysaccharides in addition to nutrients, including vitamins B and K. Alterations in the composition of the gut microbiota and reductions in microbial diversity are highlighted in many disease states, possibly rendering the host susceptible to infection and consequently negatively affecting innate immune function. Evidence is also emerging of microbially produced molecules with neuroactive functions that can have influences across the brain–gut axis. For example, γ-aminobutyric acid, serotonin, catecholamines and acetylcholine may modulate neural signalling within the enteric nervous system, when released in the intestinal lumen and consequently signal brain function and behaviour. Dietary supplementation with probiotics and prebiotics are the most widely used dietary adjuncts to modulate the gut microbiota. Furthermore, evidence is emerging of the interactions between administered microbes and dietary substrates, leading to the production of pharmabiotics, which may directly or indirectly positively influence human health.

Autism spectrum disorder (ASD) is characterised by deficits in the ability to socialise, communicate and use imagination, and displays of stereotypical behaviour. It is widely accepted that ASD involves a disorder in brain development. However, the real causes of the neurodevelopmental disorders associated with ASD are not clear. In this respect, it has been found that a majority of children with ASD display gastrointestinal symptoms, and an increased intestinal permeability. Moreover, large differences in microbiotic composition between ASD patients and controls have been reported. Therefore, nutrition-related factors have been hypothesised to play a causal role in the aetiology of ASD and its symptoms. Through a review of the literature, it was found that abnormalities in carbohydrate digestion and absorption could explain some of the gastrointestinal problems observed in a subset of ASD patients, although their role in the neurological and behavioural problems remains uncertain. In addition, the relationship between an improved gut health and a reduction of symptoms in some patients was evaluated. Recent trials involving gluten-free diets, casein-free diets, and pre- and probiotic, and multivitamin supplementation show contradictive but promising results. It can be concluded that nutrition and other environmental influences might trigger an unstable base of genetic predisposition, which may lead to the development of autism, at least in a subset of ASD patients. Clear directions for further research to improve diagnosis and treatment for the different subsets of the disorder are provided.

The present review summarises current knowledge and recent findings on the modulation of appetite by dietary protein, via both peripheral and central mechanisms. Of the three macronutrients, proteins are recognised as the strongest inhibitor of food intake. The well-recognised poor palatability of proteins is not the principal mechanism explaining the decrease in high-protein (HP) diet intake. Consumption of a HP diet does not induce conditioned food aversion, but rather experience-enhanced satiety. Amino acid consumption is detected by multiple and redundant mechanisms originating from visceral (during digestion) and metabolic (inter-prandial period) sources, recorded both directly and indirectly (mainly vagus-mediated) by the central nervous system (CNS). Peripherally, the satiating effect of dietary proteins appears to be mediated by anorexigenic gut peptides, principally cholecystokinin, glucagon-like peptide-1 and peptide YY. In the CNS, HP diets trigger the activation of noradrenergic and adrenergic neurons in the nucleus of the solitary tract and melanocortin neurons in the arcuate nucleus. Additionally, there is evidence that circulating leucine levels may modulate food intake. Leucine is associated with neural mechanisms involving mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK), energy sensors active in the control of energy intake, at least in the arcuate nucleus of the hypothalamus. In addition, HP diets inhibit the activation of opioid and GABAergic neurons in the nucleus accumbens, and thus inhibit food intake by reducing the hedonic response to food, presumably because of their low palatability. Future studies should concentrate on studying the adaptation of different neural circuits following the ingestion of protein diets.