Functional gastrointestinal disorders (FGIDs) refer to a group of disorders with chronic symptoms, such as abdominal pain, dysphagia, dyspepsia, diarrhea, constipation, and bloating. Among these, functional constipation significantly impacts the quality of life and is linked with comorbidities, such as anxiety and depression. The exact pathophysiology remains unclear despite the widespread occurrence. Research suggests that the gut-brain axis plays a role in FGIDs. Disruptions in the bidirectional communication between the brain and gastrointestinal (GI) tract contribute to GI symptoms and mood disturbances. The incomplete understanding of FGID pathophysiology has led to limited treatment options. Traditional treatments often focus on single symptoms and come with side effects, prompting the need for alternative approaches that address both GI and psychological components. Alternative approaches including herbal supplements offer a natural alternative to conventional medicine by promoting regularity and gut health. Abelmoschus esculentus L. or okra has a history of use in traditional medicine. Bioactive compounds such as polysaccharides and fibers found in okra offer gastroprotective benefits. Withania somnifera is a plant commonly referred to as ashwagandha. The plant root has been used for its health-promoting effects. Research supports the use of W. somnifera to help with stress and sleep. Digexin is a herbal supplement combining W. somnifera (ashwagandha) and A. esculentus (okra). It has shown promise in improving both GI regularity and mood by modulating the gut-brain axis. Clinical studies support the potential of a novel herbal supplement that aids in the management of FGIDs. This narrative review looks at FGIDs, etiologies, current treatment, and possible therapeutic supplements to aid in symptom management.

Recent insights into Parkinson\'s disease (PD), a progressive neurodegenerative disorder, suggest a significant influence of the gut microbiome on its pathogenesis and progression through the gut-brain axis. This study integrates 16S rRNA sequencing, high-throughput transcriptomic sequencing, and animal model experiments to explore the molecular mechanisms underpinning the role of gut-brain axis in PD, with a focus on short-chain fatty acids (SCFAs) mediated by the SCFA receptors FFAR2 and FFAR3. Our findings highlighted prominent differences in the gut microbiota composition between PD patients and healthy individuals, particularly in taxa such as Escherichia_Shigella and Bacteroidetes, which potentially impact SCFA levels through secondary metabolite biosynthesis. Notably, fecal microbiota transplantation (FMT) from healthy to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models significantly improved motor function, enhanced dopamine and serotonin levels in the striatum, and increased the number of dopaminergic neurons in the substantia nigra while reducing glial cell activation. This therapeutic effect was associated with increased levels of SCFAs such as acetate, propionate, and butyrate in the gut of MPTP-lesioned mice. Moreover, transcriptomic analyses revealed upregulated expression of FFAR2 and FFAR3 in MPTP-lesioned mice, indicating their crucial role in mediating the benefits of FMT on the central nervous system. These results provide compelling evidence that gut microbiota and SCFAs play a critical role in modulating the gut-brain axis, offering new insights into PD\'s etiology and potential targets for therapeutic intervention.

Depression, is a global health concern affecting nearly 280 million individuals. It not only imposes a significant burden on economies and healthcare systems but also manifests complex physiological connections and consequences. Agmatine, a putative neuromodulator derived primarily from beneficial gut microbes specially Lactobacillus, has emerged as a potential therapeutic agent for mental health. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of agmatine. Therefore, this study aimed to investigate the potential mechanism of agmatine in antibiotic-induced dysbiosis and depression-like behaviour in rats, focusing on its modulation of the gut-brain axis. Depression-like behavior associated with dysbiosis was induced through a seven-day regimen of the oral broad-spectrum antibiotic combination, comprising ampicillin and metronidazole and validated through microbial, biochemical, and behavioral alterations. On day 8, antibiotic-treated rats exhibited loose fecal consistency, altered fecal microbiota, and depression-like behavior in forced swim test. Pro-inflammatory cytokines were enhanced, while agmatine and monoamine levels decreased in the hippocampus and prefrontal cortex. Antibiotic administration disrupted tight junction proteins in the ileum, affecting gut architecture. Oral agmatine alone or combined with probiotics significantly reversed antibiotic-induced dysbiosis, restoring gut microbiota and mitigating depression-like behaviors. This intervention also restored neuro-inflammatory markers, increased agmatine and monoamine levels, and preserved gut integrity. The study highlights the regulatory role of endogenous agmatine in the gut-brain axis in broad-spectrum antibiotic induced dysbiosis and associated depression-like behaviour.

Increasing attention is being afforded to understanding the bidirectional relationship that exists between oral drugs and the gut microbiota. Often overlooked, however, is the impact that pharmaceutical excipients exert on the gut microbiota. Subsequently, in this study, we contrasted the pharmacokinetic performance and gut microbiota interactions between two commonly employed formulations for poorly soluble compounds, namely 1) an amorphous solid dispersion (ASD) stabilised by poly(vinyl pyrrolidone) K-30, and 2) a lipid nanoemulsion (LNE) comprised of medium chain glycerides and lecithin. The poorly soluble antipsychotic, lurasidone, was formulated with ASD and LNE due to its rate-limiting dissolution, poor oral bioavailability, and significant food effect. Both the ASD and LNE were shown to facilitate lurasidone supersaturation within in vitro dissolution studies simulating the gastrointestinal environment. This translated into profound improvements in oral pharmacokinetics in rats, with the ASD and LNE exerting comparable ∼ 2.5-fold improvements in lurasidone bioavailability, compared to the pure drug. The oral formulations imparted contrasting effects on the gut microbiota, with the LNE depleting the richness and abundance of the microbial ecosystem, as evidenced through reductions in alpha diversity (Chao1 index) and operational taxonomical units (OTUs). In contrast, the ASD exerted a \'gut neutral\' effect, whereby a mild enrichment of alpha diversity and OTUs was observed. Importantly, this suggests that ASDs are effective solubility-enhancing formulations that can be used without comprising the integrity of the gut microbiota - an integral consideration in the treatment of mental health disorders, such as schizophrenia, due to the role of the gut microbiota in regulating mood and cognition.

Schizophrenia is a severe, chronic psychiatric disorder characterized by delusions, hallucinations, cognitive impairments, and emotional dysregulation. This psychiatric illness is often resistant to treatment. This literature review aims to analyze the relationship between this complex psychological disorder and the gut microbiota found within the human body. The brain and gut are interconnected, and emerging research suggests a link between gut dysbiosis and schizophrenia. Gut dysbiosis refers to an imbalance or disruption in the composition and function of the gut microbiome. The studies comparing the gut microbiota of patients with schizophrenia to those without highlight significant differences at the phylum and genus levels, providing evidence of gut microbiome alteration. The lack of diversity of microbiota in schizophrenia patients can be altered and improved to a healthier microbiome by way of dietary intervention. Interventions that target the gut-brain axis, such as dietary probiotics or prebiotics, may help alleviate certain symptoms of schizophrenia and help improve patients\' well-being. Understanding the complex interplay between gut microbiome health and schizophrenia may allow for the development of targeted interventions that alter the gut microbiome of patients with schizophrenia and, in turn, mitigate their symptoms and improve their quality of life.

BACKGROUND: The gut-brain axis is a bidirectional communication network linking the gastrointestinal tract and the central nervous system via neuronal, hormonal, and antibody signaling pathways. Central to this connection is gut health, encompassing the balance and functionality of gut microbiota, which significantly impacts on mental and cognitive health. This study investigates the association between gut health and cognitive functioning in adults, highlighting the mechanisms by which gut microbiota influence brain health.
OBJECTIVE: To examine the effects of gut health on adult cognitive performance, with a focus on the processes by which gut microbiota impacts brain health.
METHODS: A quantitative cross-sectional study was conducted in Islamabad from January 2024 to April 2024, involving 140 adult participants. Data were collected using a comprehensive 16-item gut health questionnaire and the cognition self-assessment rating scale (C-SARS). The psychometric properties of these scales were assessed, and the data were analyzed using Statistical Product and Service Solutions (SPSS, v26; IBM SPSS Statistics for Windows, Armonk, NY). Analytical and descriptive statistics, including regression, chi-square, independent sample t-tests, and mean and standard deviation, were applied.
RESULTS: The study found moderate associations between gut health and cognitive performance, particularly in memory and processing speed (R² = 0.17, β = -1.9, p = 0.12 for general cognition; R² = 0.01, β = -0.98, p = 0.02 for memory; R² = 0.03, β = -0.18, p = 0.03 for processing speed). Gender and marital status differences were significant, with males exhibiting better gut health scores than females (M = 34.1, SD = 3.2 vs. M = 31.2, SD = 3.2, p = 0.00), and singles showing better cognitive performance compared to married individuals (M = 9.4, SD = 5.4 vs. M = 6.5, SD = 3.7, p = 0.03).
CONCLUSIONS: The study highlights significant associations between gut health and cognitive functions, suggesting that gut microbiota composition can influence cognitive performance. Gender and marital status differences underscore the need to consider individual differences in gut-brain axis research. Future studies should replicate these findings in larger samples and explore gut microbiota-targeted interventions for cognitive health enhancement.

Alzheimer\'s disease (AD) is a progressive degenerative neurological condition characterized by cognitive decline, primarily affecting memory and logical thinking, attributed to amyloid-β plaques and tau protein tangles in the brain, leading to neuronal loss and brain atrophy. Neuroinflammation, a hallmark of AD, involves the activation of microglia and astrocytes in response to pathological changes, potentially exacerbating neuronal damage. The gut-brain axis is a bidirectional communication pathway between the gastrointestinal and central nervous systems, crucial for maintaining brain health. Phytochemicals, natural compounds found in plants with antioxidant and anti-inflammatory properties, such as flavonoids, curcumin, resveratrol, and quercetin, have emerged as potential modulators of this axis, suggesting implications for AD prevention. Intake of phytochemicals influences the gut microbial composition and its metabolites, thereby impacting neuroinflammation and oxidative stress in the brain. Consumption of phytochemical-rich foods may promote a healthy gut microbiota, fostering the production of anti-inflammatory and neuroprotective substances. Early dietary incorporation of phytochemicals offers a non-invasive strategy for modulating the gut-brain axis and potentially reducing AD risk or delaying its onset. The exploration of interventions targeting the gut-brain axis through phytochemical intake represents a promising avenue for the development of preventive or therapeutic strategies against AD initiation and progression.

The gastrointestinal (GI) tract, home to the largest microbial population in the human body, plays a crucial role in overall health through various mechanisms. Recent advancements in research have revealed the potential implications of gut-brain and vice-versa communication mediated by gut-microbiota and their microbial products in various diseases including type-2 diabetes and Alzheimer\'s disease (AD). AD is the most common type of dementia where most of cases are sporadic with no clearly identified cause. However, multiple factors are implicated in the progression of sporadic AD which can be classified as non-modifiable (e.g., genetic) and modifiable (e.g. Type-2 diabetes, diet etc.). Present review focusses on key players particularly the modifiable factors such as Type-2 diabetes (T2D) and diet and their implications in microbiota-gut-brain (MGB) and brain-gut (BG) communication and cognitive functions of healthy brain and their dysfunction in Alzheimer\'s Disease. Special emphasis has been given on elucidation of the mechanistic aspects of the impact of diet on gut-microbiota and the implications of some of the gut-microbial products in T2D and AD pathology. For example, mechanistically, HFD induces gut dysbiosis with driven metabolites that in turn cause loss of integrity of intestinal barrier with concomitant colonic and systemic chronic low-grade inflammation, associated with obesity and T2D. HFD-induced obesity and T2D parallel neuroinflammation, deposition of Amyloid β (Aβ), and ultimately cognitive impairment. The review also provides a new perspective of the impact of diet on brain-gut and microbiota-gut-brain communication in terms of transcription factors as a commonly spoken language that may facilitates the interaction between gut and brain of obese diabetic patients who are at a higher risk of developing cognitive impairment and AD. Other commonality such as tyrosine kinase expression and functions maintaining intestinal integrity on one hand and the phagocytic clarence by migratory microglial functions in brain are also discussed. Lastly, the characterization of the key players future research that might shed lights on novel potential pharmacological target to impede AD progression are also discussed.

Psychedelics have emerged as promising therapeutics for several psychiatric disorders. Hypotheses around their mechanisms have revolved around their partial agonism at the serotonin 2 A receptor, leading to enhanced neuroplasticity and brain connectivity changes that underlie positive mindset shifts. However, these accounts fail to recognise that the gut microbiota, acting via the gut-brain axis, may also have a role in mediating the positive effects of psychedelics on behaviour. In this review, we present existing evidence that the composition of the gut microbiota may be responsive to psychedelic drugs, and in turn, that the effect of psychedelics could be modulated by microbial metabolism. We discuss various alternative mechanistic models and emphasize the importance of incorporating hypotheses that address the contributions of the microbiome in future research. Awareness of the microbial contribution to psychedelic action has the potential to significantly shape clinical practice, for example, by allowing personalised psychedelic therapies based on the heterogeneity of the gut microbiota.

BACKGROUND: Metabolic syndrome (MetS) is highly prevalent in individuals with schizophrenia (SZ), leading to negative consequences like premature mortality. Gut dysbiosis, which refers to an imbalance of the microbiota, and chronic inflammation are associated with both SZ and MetS. However, the relationship between gut dysbiosis, host immunological dysfunction, and SZ comorbid with MetS (SZ-MetS) remains unclear. This study aims to explore alterations in gut microbiota and their correlation with immune dysfunction in SZ-MetS, offering new insights into its pathogenesis.
RESULTS: We enrolled 114 Chinese patients with SZ-MetS and 111 age-matched healthy controls from Zhejiang, China, to investigate fecal microbiota using Illumina MiSeq sequencing targeting 16 S rRNA gene V3-V4 hypervariable regions. Host immune responses were assessed using the Bio-Plex Pro Human Cytokine 27-Plex Assay to examine cytokine profiles. In SZ-MetS, we observed decreased bacterial α-diversity and significant differences in β-diversity. LEfSe analysis identified enriched acetate-producing genera (Megamonas and Lactobacillus), and decreased butyrate-producing bacteria (Subdoligranulum, and Faecalibacterium) in SZ-MetS. These altered genera correlated with body mass index, the severity of symptoms (as measured by the Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms), and triglyceride levels. Altered bacterial metabolic pathways related to lipopolysaccharide biosynthesis, lipid metabolism, and various amino acid metabolism were also found. Additionally, SZ-MetS exhibited immunological dysfunction with increased pro-inflammatory cytokines, which correlated with the differential genera.
CONCLUSIONS: These findings suggested that gut microbiota dysbiosis and immune dysfunction play a vital role in SZ-MetS development, highlighting potential therapeutic approaches targeting the gut microbiota. While these therapies show promise, further mechanistic studies are needed to fully understand their efficacy and safety before clinical implementation.