Cancer is a long-term illness that involves an imbalance in cellular and immune functions. It can be caused by a range of factors, including exposure to environmental carcinogens, poor diet, infections, and genetic alterations. Maintaining a healthy gut microbiome is crucial for overall health, and short-chain fatty acids (SCFAs) produced by gut microbiota play a vital role in this process. Recent research has established that alterations in the gut microbiome led to decreased production of SCFA's in lumen of the colon, which associated with changes in the intestinal epithelial barrier function, and immunity, are closely linked to colorectal cancer (CRC) development and its progression. SCFAs influence cancer progression by modifying epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNA functions thereby affecting tumor initiation and metastasis. This suggests that restoring SCFA levels in colon through microbiota modulation could serve as an innovative strategy for CRC prevention and treatment. This review highlights the critical relationship between gut microbiota and CRC, emphasizing the potential of targeting SCFAs to enhance gut health and reduce CRC risk.

The gut-brain axis is regarded as the "second brain" of the host. Gut microbiota and their metabolites affect intestinal homeostasis, function, and phenotype by regulating bidirectional communication between the gut and brain. This serves as a vital strategy for understanding how gut microbiota regulate nutrient metabolism and adaptability in animals. This study explored the metabolic mechanisms through which Tibetan sheep adapt to high-altitude environments via the rumen microbiota-gut-brain axis across different phenological periods (returning-green period, fresh grass period and withered grass period). By analyzing metabolic indicators, neurotransmitters, and gene and protein expression in serum, rumen, adipose, and hypothalamic tissues, we discovered that energy metabolism markers (creatine kinase, lactate dehydrogenase, glucose) and immunoglobulins (IgG, IgM) in the serum were significantly elevated during the fresh grass period (P < 0.05). In contrast, thyroid hormones T3 and T4 were at higher levels during the returning-green period (P < 0.05). The density of rumen fiber-degrading bacteria was higher during the returning-green period (P < 0.05). Meanwhile, the densities of Butyrivibrio fibrisolvens, Selenomonas ruminantium, and Treponema bryantii microbiota significantly during the fresh grass period and were positively correlated with isovaleric acid concentration (P < 0.05). Neurotransmitters (5-HT, DOPAC, 5-HIAA, and NE) were significantly elevated in both the rumen epithelium and hypothalamus during the fresh grass period (P < 0.05). The analysis of the cAMP-PKA-pCREB pathway showed that the genes and proteins of UCP1, PKA, and CREB1 were highly expressed in adipose tissue during the fresh grass and withered grass periods, and there significant negative correlations to specific microbiota (P < 0.05). In summary, Tibetan sheep adapt to high-altitude environments through the rumen microbiota-gut-brain axis, regulating metabolic and neurotransmitter changes to establish a unique metabolic adaptation mechanism.

The influence of the gut microbiome on the human brain, especially its associations with psychiatric disorders, has emerged as a focal area in contemporary neuroscience and psychiatry research. In this study, we employed a mediation Mendelian randomization approach to delve into the potential causal relationships between gut microbiota and psychiatric disorders, with a focus on the mediating role of brain structural changes. We harnessed genetic data from large - scale genome - wide association studies to analyze how 196 gut microbiota taxa affect ten psychiatric disorders via alterations in 3,143 brain structures. Our key findings revealed significant bidirectional causal relationships. In the gut microbiota - brain structure relationship, certain gut microbiota taxa, such as Bacteroides and Marvinbryantia, were associated with changes in brain activity and white matter integrity respectively. Conversely, brain structures like the right hippocampus and left superior cerebellar peduncle influenced gut microbiota composition. Regarding gut microbiota and psychiatric disorders, we identified numerous associations. For example, the genus Prevotellaceae was significantly associated with an increased risk of Autism Spectrum Disorder, while Ruminococcaceae UCG005 showed a protective effect. In Panic Disorder, Alistipes was positively associated, and for Schizophrenia, both protective (Barnesiella) and risk - associated (Phascolarctobacterium) genera were found. Moreover, through mediation analysis, we found that brain structures mediated the effects of gut microbiota on five psychiatric disorders, including bipolar disorder and anorexia nervosa. In these cases, the influence of gut microbiota on the disorders was fully transmitted through changes in brain structure. Overall, our research clarifies the role of the microbiota - gut - brain axis in mental health. It offers a new perspective on how intestinal microbes impact brain physiology and psychiatric pathology. These findings not only deepen our understanding of the biological interactions between the gut and brain but also suggest that targeted gut microbiota modifications could be novel therapeutic strategies for mental health disorders.

The gut microbiota influences systemic immunity and the function of distal tissues, including the brain, liver, skin, lung, and muscle. However, the role of the gut microbiota in the foreign body response and fibrosis is largely unexplored. To investigate this connection, we perturbed the homeostasis of the murine gut microbiota via infection with the pathogenic bacterial species enterotoxigenic Bacteroides fragilis (ETBF) and implanted particulate material (mean particle size <600 μm) of the synthetic polymer polycaprolactone (PCL) into a distal muscle injury. ETBF infection in mice led to increased neutrophil and γδ T cell infiltration into the PCL implant site. ETBF infection alone promoted systemic inflammation, increased levels of neutrophils in lymphoid tissues, and altered skeletal muscle gene expression. At the PCL implant site, we found significant changes in the transcriptome of sorted stromal cells between infected and control mice, including differences related to ECM components such as proteoglycans and glycosaminoglycans. However, we did not observe ETBF-induced differences in fibrosis levels. These results demonstrate the ability of the gut microbiota to mediate long-distance effects such as immune and stromal responses to a distal biomaterial implant.

The pathogenesis of obesity is complex and incompletely understood, with an underlying interplay between our genetic architecture and obesogenic environment. The public understanding of the development of obesity is shrouded in myths with widespread societal misconceptions. Body Mass Index (BMI) is a highly heritable trait. However, despite reports from recent genome-wide association studies, only a small proportion of the overall heritability of BMI is known to be lurking within the human genome. Other non-genetic heritable traits may contribute to BMI. The gut microbiome is an excellent candidate, implicating complex interlinks with hypothalamic control of appetite and metabolism via entero-endocrine, autonomic, and neuro-humeral pathways. The neonatal gut microbiome derived from the mother via transgenerational transmission (vaginal delivery and breastfeeding) tends to have a permanence within the gut. Conversely, non-maternally derived gut microbiota manifest mutability that responds to changes in lifestyle and diet. We should all strive to optimize our lifestyles and ensure a diet that is replete with varied and unprocessed plant-based foods to establish and nurture a healthy gut microbiome. Women of reproductive age should optimize their gut microbiome, particularly pre-conception, ante- and postnatally to enable the establishment of a healthy neonatal gut microbiome in their offspring. Finally, we should redouble our efforts to educate the populace on the pathogenesis of obesity, and the role of heritable (but modifiable) factors such as the gut microbiome. Such renewed understanding and insights would help to promote the widespread adoption of healthy lifestyles and diets, and facilitate a transition from our current dispassionate and stigmatized societal approach towards people living with obesity towards one that is epitomized by understanding, support, and compassion.

Supplementation with probiotics seems to confer protective effects in individuals with schizophrenia (SZ), although available results are inconclusive. The aim of this study was to systematically review existing randomized clinical trials (RCTs) to critically assess the effect of probiotics on psychiatric symptoms, anthropometric indicators, lipid profiles, glycemic indices, inflammation, and oxidative stress in adults with SZ. A systematic search was conducted in four databases from inception until January 2025. Six RCTs were included in the quantitative analysis that demonstrated beneficial effects of probiotics on SZ severity determined via the Positive and Negative Syndrome Scale (PANSS), with significant reductions in PANSS (MD = -0.50, p = 0.001), PANSS Negative (MD = -0.31, p = 0.050), and PANSS General scores (MD = -0.33, p = 0.036), alongside reductions in body weight (MD = -0.92, p = 0.000), body mass index (MD = -0.53, p = 0.016), and total cholesterol (SMD = -0.34, p = 0.005). Furthermore, probiotic interventions reduced baseline glucose (SMD = -0.59, p = 0.000), insulin (MD = -0.68, p = 0.000), and measures of insulin sensitivity/resistance and significantly improved biomarkers of inflammation and oxidative stress. To summarize, this meta-analysis suggests that probiotics may confer beneficial effects in patients with SZ through improving psychiatric symptoms as well as markers of body weight, lipid and glucose metabolism, inflammation, and oxidative stress.

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is marked by cognitive decline, neuroinflammation, and neuronal loss. MicroRNAs (miRNAs) have emerged as critical regulators of gene expression, influencing key pathways involved in neuroinflammation and neurodegeneration in AD. This review delves into the multifaceted role of exercise in modulating miRNA expression and its interplay with the gut microbiome, proposing a comprehensive framework for neuroprotection in AD. By synthesizing current research, we elucidate how exercise-induced changes in miRNA profiles can mitigate inflammatory responses, promote neurogenesis, and reduce amyloid-beta and tau pathologies. Additionally, we explore the gut-brain axis, highlighting how exercise-driven alterations in gut microbiota composition can further influence miRNA expression, thereby enhancing cognitive function and reducing neuroinflammatory markers. This holistic approach underscores the potential of targeting exercise-regulated miRNAs and gut microbiome interactions as a novel, noninvasive therapeutic strategy to decelerate AD progression and improve quality of life for patients. This approach aims to decelerate disease progression and improve patient outcomes, offering a promising avenue for enhancing the effectiveness of AD management.

In both humans and rodents, inappropriate feeding times during pregnancy can cause maternal metabolic abnormalities, increasing the risk of neurodevelopmental disorders in both the mother and offspring. Using a rat model, this study investigates whether feeding only during the inactive phase in rats leads to anxiety-like behaviors and abnormal brain development in fetuses through gut microbiota imbalance.

10-week-old female rats in the inactive-phase feeding group (IF group) were first trained for daytime feeding, ensuring that energy intake was statistically insignificant and different from that of the normal diet feeding group (ND group). They were then paired with male rats, and the previous feeding regimen was continued after pregnancy. Anxiety-like behavior was evaluated using the open-field test. Maternal caecal microbiota was analyzed using 16S rRNA sequencing. Enzyme-linked immunosorbent assay (ELISA) measured serum inflammation factors. RT-PCR was employed to assess mRNA levels of integrity genes and inflammatory cytokines in the maternal hippocampi, intestines, fetal brains, and placentae.

There were no statistically significant differences in energy intake or body weight gain between the IF and ND groups. In the open field test, dams in the IF group exhibited anxiety-like behavior, as indicated by fewer entries into and shorter duration in the central zone. Active-phase fasting elevated maternal serum inflammatory cytokine levels and impaired antioxidant capacity. It also increased intestinal permeability and induced gut microbiota dysbiosis, characterized by a decrease in Akkermansia and an increase in Dubosiella. Changes in the expression of intestinal circadian genes and elevated intestinal inflammatory cytokines were observed. Lipopolysaccharide (LPS) translocated into the maternal circulation, activated Toll-like receptor 4 (TLR 4), and passed through the compromised placental barrier into the fetal brain, leading to increased expression of inflammatory cytokines in the fetal brain.

The misalignment between maternal feeding time and the biological clock during pregnancy disrupts the balance of the gut microbiota and peripheral rhythms. The impaired intestinal and placental barriers allow LPS from the gut to infiltrate the maternal hippocampus and fetal brain, increasing inflammation and impacting both maternal and fetal brain health.

Appetite regulation is a lifestyle intervention strategy to maintain health. The regulatory effects of dietary fiber (especially insoluble dietary fiber), as a crucial element of the nutritional composition, on appetite remain poorly understood. This study investigated modulatory effects of konjac fiber (KF, with high and low expansion) and konjac powder (KP) on chyme digestion, gastrointestinal hormones, intestinal microbiota, appetite genes in hypothalamus, GLP-1 receptor (GLP-1R) protein in various tissues of rats by dietary intervention. The results showed that highly-expanded konjac fiber (HKF) significantly delayed gastric emptying and inhibited hydrolysis of chyme. Konjac fiber (KF), especially HKF, and KP increased short-chain fatty acid (SCFA) content and plasma glucagon-like peptide-1 (GLP-1) levels. HKF upregulated the expression of GLP-1R protein in rat stomachs, nucleus tractus solitaries (NTS), and area postrema (AP) of rat brain, but down-regulated the expression of appetite gene AgRP/NPY in hypothalamus, thus, inhibiting appetite, reducing daily food intake and weight gain. Overall, this study reveals the mechanism through which expandable konjac fiber modulates appetite and chyme digestion in vivo by stomach-intestine-brain axis. Our findings provide an insight into the regulatory effects of insoluble dietary fiber on appetite and offered a valuable reference for the development of satiety-enhancing functional foods.

Study DesignProspective cohort study.ObjectiveUnderstanding the complex nature of low back pain (LBP) is crucial for effective management. The PainDETECT questionnaire is a tool that distinguishes between neuropathic (NeP) and nociceptive (NoP) low back pain. Traditionally NeP and NoP have been primarily attributed to patho-anatomical abnormalities within the lumbar spine. However, increasing evidence points to multifaceted involvement, encompassing a range of physical, biomechanical, chemical, and psychosocial factors. The study aimed to determine the independent relationship between NeP as assessed by the PainDETECT questionnaire and non-spinal comorbid medical conditions.MethodsA prospective cohort study was conducted involving 400 patients suffering from chronic LBP (>6months), aged >18 years, who complete the PainDETECT questionnaire and provided responses regarding the presence of any comorbid conditions. A binary logistic regression model was used to analyse the confounding status of comorbid medical conditions and pain severity measured by NRS to determine independent relationships between specific conditions and neuropathic pain.ResultsThe study included 143 and 257 patients suffering from NeP and NoP, respectively. The NeP group had a 38% higher mean numerical rating scale score compared to the NoP group (8.10 ± 1.55 vs 5.86± 2.26, P < 0.001). The odds of developing NeP were 2.9 Exp(B) = 2.844, 95%C.I. [1.426-5.670], P < 0.01), 2.7 (Exp(B) = 2.726, 95%C.I. [1.183-6.283], P < 0.05) and 2.8 (Exp(B) = 2.847, 95%C.I. [1.473-5.503], P < 0.05) times higher in patients suffering from gastrointestinal conditions, rheumatoid arthritis, and depression, respectively.ConclusionNeP as determined by the PainDETECT questionnaire, is associated with gastrointestinal conditions, rheumatoid arthritis, and depression. This pioneering study has shed light on the potential involvement of the gut microbiome as a common factor connecting non-spinal comorbidities and NeP. These findings underscore the importance of formulating personalized management plans tailored to individual pain and medical profiles, rather than relying on a blanket approach to pain management.

Evidence of changes in the composition and function of the gut microbiota (GM) in post-stroke depression (PSD) patients is gradually accumulating. This study aimed to systematically evaluate the relationship between PSD and GM.

We searched in PubMed, Web of Science, Embase, Cochrane databases, Wangfang, VIP, CBM, and CNKI from the establishment of the database to April 17, 2024, and systematic review and meta-analysis were performed to investigate the differences of GM between patients with PSD spectrum and healthy controls (HC) or stroke spectrum.

There were 14 studies consisting a total of 1,556 individuals included in the meta-analysis. The pooled results showed that PSD spectrum demonstrated significantly increased α diversity as indexed by Chao1 index, ACE indexes, Shannon index, and Simpson index as compared to HC. Additionally, stroke spectrum significantly increased α diversity as indexed by Simpson index compared to PSD. Furthermore, the pooled estimation of relative abundance showed that Bacteroidota, Fusobacteriota, and Pseudomonadota in PSD patients were significantly higher than those in the HC group, while the abundance of Bacillota was higher in the HC group. Moreover, significant differences in GM were observed between PSD patients and HC at the family and genus levels.

This study found that the α diversity of PSD patients was higher than that of HC. Moreover, there were also differences in the distribution of GM at the phylum, family, and genus levels, respectively. At the same time, the level of Lachnospira in PSD patients was lower than that in the stroke group.

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024582708.

Chronic constipation is a prevalent, burdensome gastrointestinal disorder whose etiology and pathophysiology remain poorly understood. Differences in the composition of the intestinal microbiota have been shown between constipated patients and healthy people. Data indicate that these microbial differences contribute to the disorder.

Preclinical studies in mice examined the effects of Lactobacillus gasseri on intestinal motility ex vivo, the reversal of motility inhibition by μ-opioid receptor agonists ex vivo and in vivo in mice, and the effects on capsaicin-stimulated transient receptor potential vanilloid 1 (TRPV1) in Jurkat cells. Thereafter, a clinical study of 40 women with functional constipation was conducted to investigate the effects of Lactobacillus gasseri with a randomized parallel design. After 14 days of baseline recording, treatment with Lactobacillus gasseri or placebo was given over 28 days, with 14 days of follow-up. Outcomes with complete spontaneous bowel movements (CSBM), spontaneous bowel movements, emptying frequency, abdominal pain, time spent for defecation, Bristol stool form scale, use of rescue laxatives, and impact on sex life were investigated.

In preclinical studies, Lactobacillus gasseri increased intestinal motility in an ex vivo model, reversed the motility inhibition caused by μ-opioid receptor agonist ex vivo and in vivo in mice, and counteracted capsaicin-stimulated activity of TRPV1 in Jurkat cells. In the clinical trial, Lactobacillus gasseri showed a significant reduction in abdominal pain, along with a correlation and tendency for an increased number of CSBM. Few adverse events were encountered.

Treatment with Lactobacillus gasseri can alleviate pain sensations in functional constipation, possibly with an improved bowel-emptying function.

BackgroundProbiotics, as common regulators of the gut microbiota, have been used in research to alleviate clinical symptoms of atopic dermatitis (AD).ObjectiveOur research team has previously identified a potential relieving effect of Clostridium butyricum on the treatment of AD, but the specific mechanism of how Clostridium butyricum alleviates AD has not yet been confirmed.MethodsIn this study, we explored the relieving effect of Clostridium butyricum on AD through in vivo and in vitro experiments. AD mice induced by 2,4-dinitrofluorobenzene (DNFB) were orally administered with 1 × 108 CFU of Clostridium butyricum for three consecutive weeks.ResultsOral administration of Clostridium butyricum reduced ear swelling, alleviated back skin lesions, decreased mast cell and inflammatory cell infiltration, and regulated the levels of inflammation-related cytokines. Clostridium butyricum activated the intestinal immune system through the TLR4/MyD88/NF-κB signaling pathway, suppressed the expression of inflammatory factors IL-10 and IL-13, and protected the damaged intestinal mucosa.ConclusionClostridium butyricum administration improved the diversity and abundance of the gut microbiota, enhanced the functionality of the immune system, and protected the epidermal barrier.

The study aimed to investigate the association of sleep bruxism (SB) and awake bruxism (AB) with health-related factors.

Data on bruxism and diagnosed diseases, use of psychoactive substances and regular identified psychoactive drugs were collected from 1,962 subjects in the Northern Finland Birth Cohort 1966 through a questionnaire. The associations were analyzed using chi-square tests and binary regression models, adjusting for gender and education, and for anxiety/depression symptoms.

Migraine and gastric/duodenal disorders, use of serotonergic antidepressants and a high number of psychoactive drugs associated significantly with AB and SB. Gastrointestinal diseases associated with SB. Poor general health and hand eczema associated with AB. Based on the multivariate model, depression/anxiety symptoms seemed to mediate the associations of bruxism with depression, hand eczema, self-reported gastric/duodenal disorders and the number of identified drugs.

Several diseases, depression/anxiety symptoms and psychoactive medications were associated with SB and AB, the associations being stronger with AB than SB.

There is an escalating need to comprehend the long-term impacts of nuclear radiation exposure since the permeation of ionizing radiation has been frequent in our current societal framework. A system evaluation of the microbes that reside inside a host's colon could meet this knowledge gap since the microbes play major roles in a host's response to stress. Indeed, our past study suggested that these microbes might break their symbiotic association with moribund hosts to form a pro-survival condition exclusive to themselves. In this study, we undertook metagenomics and metabolomics assays regarding the descending colon content (DCC) of adult mice. DCCs were collected 1 month and 6 months after 7 Gy or 7.5 Gy total body irradiation (TBI). The assessment of the metagenomic diversity profile in DCC found a significant sex bias caused by TBI. Six months after 7.5 Gy TBI, decreased Bacteroidetes were replaced by increased Firmicutes in males, and these alterations were reflected in the functional analysis. For instance, a larger number of networks linked to small chain fatty acid (SCFA) synthesis and metabolism were inhibited in males than in females. Additionally, bioenergy networks showed regression dynamics in females at 6 months post-TBI. Increased accumulation of glucose and pyruvate, which are typical precursors of beneficial SCFAs coupled with the activated networks linked to the production of reactive oxygen species, suggest a cross-sex energy-deprived state. Overall, there was a major chronic adverse implication in male mice that supported the previous literature in suggesting females are more radioresistant than males. The sex-biased chronic effects of TBI should be taken into consideration in designing the pertinent therapeutics.

Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca2+ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.

Depression, a major global health issue, is closely associated with imbalances in gut microbiota and altered intestinal functions. This study investigates the antidepressant potential of a composite of Geniposide (GP) and Nanocrystalline Cellulose (NCC), focusing on its effects on the gut-brain axis. Utilizing network pharmacology, GP was identified as a key compound targeting the BCL2 gene in depression management. Experimental approaches, including a chronic unpredictable mild stress (CUMS) model in mice, cellular assays, and fecal microbiota transplantation (FMT), were used to evaluate the composite's effectiveness. Results indicate that GP activates the adenosine monophosphate-activated protein kinase (AMPK) pathway by upregulating BCL2, enhancing intestinal barrier integrity, and balancing gut flora. These mechanisms contribute to its positive effects on hippocampal function and depressive-like behaviors in mice, suggesting that the GP-NCC composite could be a promising avenue for developing depression therapies that target gut health.

Antibacterials are among the most frequently prescribed medications. Antibacterial drugs have the unintended consequence of destroying healthy gut flora, which can lead to known adverse events such as Clostridium difficile infection. Given emerging research concerning the role of these microorganisms in the gut-brain axis and some limited epidemiological studies, the objective of this study was to determine if antimicrobial exposure is associated with increased risk for depression.

National Veterans Health Administration administrative data were used to identify 878,405 veteran patients prescribed an incident antimicrobial during calendar year 2018. Sequence symmetry analysis was used to compare the incidence of a depressive disorder in the 6 months before and after antibacterial exposure, with additional analyses conducted with other antimicrobial classes as negative controls including antifungals, antivirals, and nonsystemic antibacterials.

Antibacterial initiation was associated with a small but significant increase in the risk of incident depression (symmetry ratio [SR] = 1.04, 95% confidence interval [CI]: 1.03, 1.05), which was limited to the first 8 weeks following exposure. The strength of association varied with categories of antibacterial spectrum, from SR = 0.98 (95% CI: 0.95, 1.01) with the narrowest spectrum regimens, to SR = 1.12 (95% CI: 1.09, 1.15) with the broadest regimens. No significant association with incident depression was observed for antifungals, antivirals, and nonsystemic antibacterials.

Antibacterial exposure was associated with increased risk for a depressive disorder. These findings are consistent with emerging literature and support the need for further research investigating a causal relationship between antibacterial exposure and risk for adverse mental health outcomes.

The microbiota-gut-brain axis has been implicated in the pathology of substance use disorders (SUDs). In light of the brain's capability to reorganize itself in response to intrinsic and extrinsic stimuli, opioid-induced dysbiosis is likely to contribute to addictive behaviour through modulating neuroplasticity. In this study, a faecal microbiota transplantation (FMT) from a saline-donor was performed on morphine-treated rats to evaluate the effects of gut microbiota on morphine-induced metaplasticity and addictive behaviours. Male Wistar rats were treated with subcutaneous injections of 10 mg/kg morphine sulphate every 12 h for 9 days in an effort to induce dependence. The withdrawal syndrome was precipitated by injecting naloxone (1.5 mg/kg, ip) after the final dose of morphine. The tolerance was induced by repeated morphine injections over a period of 7 days (10 mg/kg, once a day, ip). FMT was applied daily through gavage of processed faeces 1 week before and during the morphine treatment. Field potential recordings (i.e., fEPSP) were carried out to assess short-term and long-term synaptic plasticity in the CA1 area of the hippocampus following Schaffer-collateral stimulation. Animals subjected to FMT exhibited significant reductions in naloxone-precipitated withdrawal syndrome (one-way ANOVA, p < 0.05). Tolerance to the analgesic effects of morphine was not affected by FMT (two-way ANOVA, p > 0.05). Following high-frequency stimulation (HFS) to induce long-term potentiation (LTP), a greater fEPSP slope was observed in morphine-treated animals (unpaired t test, p < 0.05). FMT from saline-donor rats diminished morphine-induced augmented LTP (unpaired t test, p < 0.05). These results highlighted the alleviating effects of FMT from saline-donors on morphine-induced metaplasticity and dependence potentially by modulating the dysbiosis of gut microbiota.

Postpartum depressive symptoms (PDS) are a common mental health condition among women after delivery. Although various causative factors have been reported, PDS remains a challenging condition to predict and prevent. The disruption of the gut microbiota due to antibiotic exposure has been reported to affect psychiatric conditions. Similarly, previous research suggests that antibiotic exposure during pregnancy could be related to PDS. Therefore, this prospective study examines the association between antibiotic exposure during pregnancy and PDS for 6 months after delivery. Data were obtained from 65,272 mothers from the Japan environment and children's study, a prospective birth cohort study. The ratios of maternal PDS at 1 and 6 months after delivery were 12.3% and 10.1%, respectively. During pregnancy, 10.7% of women took antibiotics orally. Antibiotic exposure during pregnancy was associated with an increased risk of PDS only at 6 months after delivery (OR = 1.13, 95% CI [1.00, 1.26]), adjusted for potential confounding factors. An increase in Edinburgh Postnatal Depression Scale scores in relation to antibiotic exposure during pregnancy was primarily observed via psychological distress during pregnancy. Although a causal link was not established, antibiotic exposure during pregnancy may be a contributing risk factor for PDS. Therefore, when antibiotic administration is required, clinical practitioners and perinatal care providers should consider the potential risk for PDS.

Gut microbiome is implicated in the onset and progression of major depressive disorder (MDD), but the dynamic alterations of depressive symptoms, gut microbiome, and fecal metabolome across different stages of stress exposure remain unclear. Here, we modified the chronic social defeat stress (CSDS) model to evaluate mice subjected to social defeat stress for 1, 4, 7, and 10 days. Behavioral tests, 16S rRNA, metagenomics, and fecal metabolomics were conducted to investigate the impact of stress exposure on behaviors, gut microbiota and fecal metabolites. We observed that depressive-like behaviors, such as anhedonia and social avoidance, worsened significantly as stress exposure increased. The microbial composition, function, and fecal metabolites exhibited distinct separations across the different social defeat stress groups. Mediation analysis identified key bacteria, such as Lachnospiraceae_UCG-001 and Bacteroidetes, and fecal metabolites like valeric acid and N-acetylaspartate. In our clinical depression cohort, we confirmed that fecal valeric acid levels, were significantly lower in depressive-like mice and MDD patients, correlating closely with stress exposure and anhedonia in mice. Further analysis of serum and brain metabolites in mice revealed sustained changes of N-acetylaspartate abundance in fecal, serum, and cortical samples following increasing stress exposure. Together, this study elucidated the characteristics of depressive-like behaviors, gut microbiome, and fecal metabolome across various social defeat stress exposure, and identified key bacteria and fecal metabolites potentially involved in modulating social defeat stress response and depressive-like behaviors, providing new insights into the pathogenesis and intervention of depression.

The human gut microbiota is diverse and abundant and plays important roles in regulating health by participating in metabolism and controlling physiological activities. The gut microbiota and its metabolites have been shown to affect the functioning of the gut and central nervous system through the microbiota-gut-brain axis. It is well established that microbiota play significant roles in the pathogenesis and progression of Parkinson's disease (PD). Disorders of the intestinal microbiota and altered metabolite levels are closely associated with PD. Here, the changes in intestinal microbiota and effects of metabolites in patients with PD are reviewed. Potential mechanisms underlying intestinal microbiota disorders in the pathogenesis of PD are briefly discussed. Additionally, we outline the current strategies for the treatment of PD that target the gut microbiota, emphasizing the development of promising novel strategies.

Ischemic stroke (IS) is a cerebrovascular disease that predominantly affects middle-aged and elderly populations, exhibiting high mortality and disability rates. At present, the incidence of IS is increasing annually, with a notable trend towards younger affected individuals. Recent discoveries concerning the "gut-brain axis" have established a connection between the gut and the brain. Numerous studies have revealed that intestinal microbes play a crucial role in the onset, progression, and outcomes of IS. They are involved in the entire pathophysiological process of IS through mechanisms such as chronic inflammation, neural regulation, and metabolic processes. Although numerous studies have explored the relationship between IS and intestinal microbiota, comprehensive analyses of specific microbiota is relatively scarce. Therefore, this paper provides an overview of the typical changes in gut microbiota following IS and investigates the role of specific microorganisms in this context. Additionally, it presents a comprehensive analysis of post-stroke microbiological therapy and the relationship between IS and diet. The aim is to identify potential microbial targets for therapeutic intervention, as well as to highlight the benefits of microbiological therapies and the significance of dietary management. Overall, this paper seeks to provide key strategies for the treatment and management of IS, advocating for healthy diets and health programs for individuals. Meanwhile, it may offer a new perspective on the future interdisciplinary development of neurology, microbiology and nutrition.

Inflammatory bowel disease (IBD) is associated with neuroinflammation, which may contribute to an increased risk of neurodegenerative disorders. This research investigated the potential of transcranial low-intensity pulsed ultrasound (LIPUS) to mitigate colonic inflammation induced by dextran sulphate sodium (DSS), focusing on its effects via the brain-gut axis. Colitis and neuroinflammation were induced in mice by administering 3% (wt/vol) DSS for 7 days. Subsequently, the brain was subjected to LIPUS stimulation at intensities of 0.5 or 1.0 W/cm² for 3 days. Biological samples were analyzed using real-time polymerase chain reaction, western blot, enzyme-linked immunosorbent assay, and histological observation. Behavioural dysfunctions were assessed using the open field test, novel object recognition task, and Y-maze test. The alteration in gut microbiota composition was assessed through 16S rRNA sequencing. LIPUS therapy notably alleviated colitis symptoms and suppressed inflammation in both the colon and hippocampus of DSS-exposed mice. Compared with the group treated only with DSS, the LIPUS treatment showed decreased crypt destruction and partial epithelial barrier preservation. Moreover, LIPUS preserved intestinal barrier function by upregulating the levels of occludin and zonula occludens, decreasing the levels of lipopolysaccharide (LPS) and LPS-binding protein in serum, and ameliorating behavioural disorders. Further analysis indicated that LIPUS did not significantly transform the composition of the intestinal microbiota, but the microbial community showed some differences from the community in the DSS-only treatment group. This study demonstrates that transcranial LIPUS stimulation could be a novel therapeutic strategy for IBD and neuroinflammation via regulation of inflammatory interactions across brain-gut axis.

Background: The gut microbiome (GM) has been reported to play a role in traumatic brain injury (TBI). To investigate the causal relationship between GMs, inflammatory mediators, and TBI, a comprehensive Mendelian randomization (MR) analysis was conducted. Methods: We utilized Genome-Wide Association Study (GWAS) summary statistics to examine the causal relationships between GM and TBI. To assess the potential causal associations between GM and TBI, we employed the inverse-variance-weighted, MR-Egger, and weighted median methods. Mediation analysis was used to assess the possible mediating factors. Several sensitivity analyses methods were implemented to verify the stability of the results. Additionally, we utilized FUMA GWAS to map single-nucleotide polymorphisms to genes and conduct transcriptomic MR analysis. Results: We identified potential causal relationships between nine bacterial taxa and TBI. Notably, class Methanobacteria, family Methanobacteriaceae, and order Methanobacteriales (p = 0.0003) maintained a robust positive correlation with TBI. This causal association passed false discovery rate (FDR) correction (FDR < 0.05). Genetically determined 1 inflammatory protein, 30 immune cells and 3 inflammatory factors were significantly causally related to TBI. None of them mediated the relationship between GMs and TBI. The outcome of the sensitivity analysis corroborated the findings. Regarding the mapped genes of significant GMs, genes such as CLK4, MTRF1, NAA16, SH3BP5, and ZNF354A in class Methanobacteria showed a significant causal correlation with TBI. Conclusions: Our study reveals the potential causal effects of nine GMs, especially Methanogens on TBI, and there was no link between TBI and GM through inflammatory protein, immune cells, and inflammatory factors, which may offer fresh insights into TBI biomarkers and therapeutic targets through specific GMs.

The microbiota-gut-brain axis is a complex communication system that plays a crucial role in influencing various aspects of our physical and mental health. The goal of this study was to determine the extent to which individual differences in resting measures of vagally-mediated heart rate variability (HRV) and cortisol levels were associated with psychometric and specific gut microbiota characteristics in seventy-five (38 females) healthy individuals. Participants were assessed for vagally-mediated HRV, daily salivary cortisol levels, psychometric characteristics, and gut microbiota composition. Using a categorical approach based on the median split of HRV and cortisol values, we identified an association between low vagally-mediated HRV, greater depressive symptomatology, and altered gut microbiota (e.g., a higher abundance of Prevotella and a smaller abundance of Faecalibacterium, Alistipes, and Gemmiger). This suggests that vagally-mediated HRV may be a useful biomarker of microbiota-gut brain axis function, and that low vagally-mediated HRV may play an important role in the bidirectional link between gut dysbiosis and depression. On the other hand, daily cortisol parameters (e.g., cortisol awakening response, diurnal cortisol slope) were associated either with higher anxiety and perceived stress, or with a specific gut microbiota profile. Therefore, their utility as biomarkers of microbiota-gut-brain axis function needs further scrutiny.

The crisis of metabolic and mental disorders continues to escalate worldwide. A growing body of research highlights the influence of tryptophan and its metabolites, such as serotonin, beyond their traditional roles in neural signaling. Serotonin acts as a key neurotransmitter within the brain-gut-microbiome axis, a critical bidirectional communication network affecting both metabolism and behavior. Emerging evidence suggests that the gut microbiome regulates brain function and behavior, particularly through microbial influences on tryptophan metabolism and the serotonergic system, both of which are essential for normal functioning. Additionally, sex differences exist in multiple aspects of serotonin-mediated modulation within the brain-gut-microbiome axis, affecting feeding and affective behaviors. This review summarizes the current knowledge from human and animal studies on the influence of tryptophan and its metabolite serotonin on metabolic and behavioral regulation involving the brain and gut microbiome, with a focus on sex differences and the role of sex hormones. We speculate that gut-derived tryptophan and serotonin play essential roles in the pathophysiology that modifies neural circuits, potentially contributing to eating and affective disorders. We propose the gut microbiome as an appealing therapeutic target for metabolic and affective disorders, emphasizing the importance of understanding sex differences in metabolic and behavioral regulation influenced by the brain-gut-microbiome axis. The therapeutic targeting of the gut microbiota and its metabolites may offer a viable strategy for treating serotonin-related disorders, such as eating and affective disorders, with potential differences in treatment efficacy between men and women. This review would promote research on sex differences in metabolic and behavioral regulation impacted by the brain-gut-microbiome axis.

Natural Products (NPs) are increasingly utilized worldwide for their potential therapeutic benefits, including central nervous system (CNS) disorders. Studies have shown açai berries mitigating Parkinson's disease progression through dopaminergic neuroprotection via Nrf-2 HO-1 pathways. Ashwagandha, an evergreen shrub, has shown potential as a therapeutic for neurodegenerative disorders via axonal regeneration in Aβ25-35-treated cortical neurons in vitro. In most cases, promising NPs are tested using in vitro assays or simpler systems during the early stages of drug discovery. However, a critical challenge lies in the lack of data on blood-brain barrier (BBB) penetration, which is a significant determinant for the successful development of CNS drugs. Our first goal was to test our in-house NP constituent library via the Parallel Artificial Membrane Permeability Assay (PAMPA-BBB), with the aim of understanding their BBB-penetration potential. Of the constituents tested, 255 were found to have moderate to high BBB permeability. Our next goal was to understand if these compounds could exhibit CNS toxicity. Neuronal viability and neurite outgrowth assays were performed with this subset to identify compounds with neurotoxicity potential. Around 35% of compounds tested showed neurite outgrowth inhibition. The habitual and widespread consumption of NPs underscores the importance of subjecting this subset of compounds to additional testing and validation in vivo to ascertain their potential detrimental effects. Understanding BBB permeability and assessing neurotoxicity mechanisms of NPs will significantly benefit the CNS drug discovery community.

Post-stroke depression (PSD) is one of the most common and devastating neuropsychiatric complications in stroke patients, affecting more than one-third of survivors of ischemic stroke (IS). Despite its high incidence, PSD is often overlooked or undertreated in clinical practice, and effective preventive measures and therapeutic interventions remain limited. Although the exact mechanisms of PSD are not fully understood, emerging evidence suggests that the gut microbiota plays a key role in regulating gut-brain communication. This has sparked great interest in the relationship between the microbiota-gut-brain axis (MGBA) and PSD, especially in the context of cerebral ischemia. In addition to the gut microbiota, another important factor is the gut barrier, which acts as a frontline sensor distinguishing between beneficial and harmful microbes, regulating inflammatory responses and immunomodulation. Based on this, this paper proposes a new approach, the microbiota-immune-barrier axis, which is not only closely related to the pathophysiology of IS but may also play a critical role in the occurrence and progression of PSD. This review aims to systematically analyze how the gut microbiota affects the integrity and function of the barrier after IS through inflammatory responses and immunomodulation, leading to the production or exacerbation of depressive symptoms in the context of cerebral ischemia. In addition, we will explore existing technologies that can assess the MGBA and potential therapeutic strategies for PSD, with the hope of providing new insights for future research and clinical interventions.

Disorders of Gut-Brain Interaction (DGBI) are widely prevalent and commonly encountered in gastroenterology practice. While several peripheral and central mechanisms have been implicated in the pathogenesis of DGBI, a recent body of work suggests an important role for the gut microbiome. In this review, we highlight how gut microbiota and their metabolites affect physiologic changes underlying symptoms in DGBI, with a particular focus on their mechanistic influence on GI transit, visceral sensitivity, intestinal barrier function and secretion, and CNS processing. This review emphasizes the complexity of local and distant effects of microbial metabolites on physiological function, influenced by factors such as metabolite concentration, duration of metabolite exposure, receptor location, host genetics, and underlying disease state. Large-scale in vitro work has elucidated interactions between host receptors and the microbial metabolome but there is a need for future research to integrate such preclinical findings with clinical studies. The development of novel, targeted therapeutic strategies for DGBI hinges on a deeper understanding of these metabolite-host interactions, offering exciting possibilities for the future of treatment of DGBI.

Tumors of the central nervous system (CNS), especially gliomas, pose a significant clinical challenge due to their aggressive nature and limited therapeutic options. Emerging research highlights the critical role of the gut microbiota in regulating CNS health and disease. The composition of the gut microbiota is essential for maintaining CNS homeostasis, as it modulates immune responses, oxidative status, and neuroinflammation. The microbiota-gut-brain axis, a bidirectional communication network, plays a pivotal role in cancer and CNS disease treatment, exerting its influence through neural, endocrine, immunological, and metabolic pathways. Recent studies suggest that the gut microbiota influences the solidification of the tumor microenvironment and that dysbiosis may promote glioma development by modulating systemic inflammation and oxidative stress, which contributes to tumorigenesis and CNS tumor progression. This review interrogates the impact of the gut microbiota on glioma, focusing on critical pathways such as NF-κB, MAPK, PI3K/Akt/mTOR, and Kynurenine/AhR that drive tumor proliferation, immune evasion, and therapy resistance. Furthermore, we explore emerging therapeutic strategies, including probiotics and microbiota-based interventions, which show potential in modulating these pathways and enhancing immunotherapies such as checkpoint inhibitors. By focusing on the multifaceted interactions between the gut microbiota, oxidative stress, and CNS tumors, this review highlights the potential of microbiota-targeted therapies and their manipulation to complement and enhance current treatments.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain, bloating, and altered bowel habits. Women are disproportionately affected by IBS due to a complex interplay between genetic, environmental, and psychosocial factors, along with a crucial role of the gut-brain axis in modulating both bowel function and pain perception. Evidence suggests a strong association between psychological distress and IBS symptoms. Women with IBS report higher levels of psychological distress compared to men, and sex is a biological variable that shapes several aspects of the mechanisms, epidemiology, and clinical manifestations of IBS. This paper explores the bidirectional relationship between psychological factors and IBS with a focus on women. Stress, anxiety, depression, and childhood trauma contribute to IBS symptomatology, and societal and biological factors unique to women may exacerbate this condition. Strategies for integrated care approaches and gender-specific treatment strategies to improve patient outcomes and quality of life are needed.

The hypothalamus-pituitary-adrenal (HPA) and gut-brain axes are vital biological pathways in depression. The HPA axis regulates the body's stress response, and chronic stress can lead to overactivation of the HPA axis, resulting in elevated cortisol levels that contribute to neuronal damage, particularly in regions such as the hippocampus and prefrontal cortex, both of which are involved in mood regulation and mental disorders. In parallel, the gut-brain axis, a bidirectional communication network between the gut microbiota and the central nervous system, influences emotional and cognitive functions. Imbalances in gut microbiota can affect the HPA axis, promoting inflammation and increasing gut permeability. This allows endotoxins to enter the bloodstream, contributing to neuroinflammation and altering neurotransmitter production, including serotonin. Since the majority of serotonin is produced in the gut, disruptions in this pathway may be linked to depressive symptoms. This review explores the interplay between the HPA axis and the gut-brain axis in the context of depression.

The rising prevalence of treatment-resistant neuropsychiatric disorders underscores the need for innovative and effective treatment strategies. The gut microbiota (GM) plays a pivotal role in the progression of these diseases, influencing the brain and mental health through the gut-brain axis (GBA). The vagus nerve plays a significant role in the GBA, making it a key area of focus for potential novel therapeutic interventions. Vagus nerve stimulation (VNS) was introduced and approved as a treatment for refractory forms of some neuropsychological disorders, such as depression and epilepsy. Considering its impact on several brain regions that play a vital part in mood, motivation, affection, and cognitive function, the VNS has shown significant therapeutic potential for treating a variety of neuropsychiatric disorders. Using VNS to target the bidirectional communication pathways linking the GM and the VN could present an exciting and novel approach to treating neuropsychological disorders. Imbalances in the GM, such as dysbiosis, can impair the communication pathways between the gut and the brain, contributing to the development of neuropsychological disorders. VNS shows potential for modulating these interconnected systems, helping to restore balance. Interestingly, the composition of the GM may also influence the effectiveness of VNS, as it has the potential to modify the brain's response to this therapeutic approach. This study provides a comprehensive analysis of a relatively unexplored but noteworthy interaction between VNS and GM in the treatment of neuropsychiatric disorders. In addition, we discussed the mechanisms, therapeutic potential, and clinical implications of VNS on the GBA across neuropsychiatric disorders.

Bacteria and their derivatives show great potential as drug delivery systems due to their unique chemotaxis, biocompatibility, and targeting abilities. In CNS disease treatment, bacterial carriers can cross the blood-brain barrier (BBB) and deliver drugs precisely, overcoming limitations of traditional methods. Advances in genetic engineering, synthetic biology, and nanotechnology have transformed these systems into multifunctional platforms for personalized CNS treatment.

This review examines the latest research on bacterial carriers for treating ischemic brain injury, neurodegenerative diseases, and gliomas. Bacteria efficiently cross the blood-brain barrier via active targeting, endocytosis, paracellular transport, and the nose-to-brain route for precise drug delivery. Various bacterial drug delivery systems, such as OMVs and bacterial ghosts, are explored for their design and application. Databases were searched in Google Scholar for the period up to December 2024.

Future developments in bacterial drug delivery will rely on AI-driven design and high-throughput engineering, enhancing treatment precision. Personalized medicine will further optimize bacterial carriers for individual patients, but challenges such as biosafety, immune rejection, and scalability must be addressed. As multimodal diagnostic and therapeutic strategies advance, bacterial carriers are expected to play a central role in CNS disease treatment, offering novel precision medicine solutions.

Over the past several decades, high-resolution brain imaging, blood and cerebrospinal fluid analyses, and other advanced technologies have changed diagnosis from an exercise depending primarily on the history and physical examination to a computer- and online resource-aided process that relies on larger and larger quantities of data. In addition, randomized controlled trials (RCT) at a population level have led to many new drugs and devices to treat neurological disease, including disease-modifying therapies. We are now at a crossroads. Combinatorially profound increases in data about individuals has led to an alternative to population-based RCTs. Genotyping and comprehensive "deep" phenotyping can sort individuals into smaller groups, enabling precise medical decisions at a personal level. In neurology, precision medicine that includes prediction, prevention and personalization requires that genomic and phenomic information further incorporate imaging and behavioral data. In this article, we review the genomic, phenomic, and computational aspects of precision medicine for neurology. After defining biological markers, we discuss some applications of these "-omic" and neuroimaging measures, and then outline the role of computation and ultimately brain simulation. We conclude the article with a discussion of the relation between precision medicine and value-based care.

Berberine (BBR) has been reported to mitigate epileptic seizures. However, the potential mechanism of its anti-seizure effect remains uncharacterized.

This study aimed to investigate the protective effect of BBR on acute epileptic seizures induced by kainic acid (KA) in mice and further explore its mechanism of action in the aspect of analysis of gut microbiota.

The protective effect of BBR against acute epileptic seizures was assessed via Racine score and Nissl training. Alterations of gut microbiota and metabolites in seizure mice after BBR treatment were analyzed through 16S sequencing and lipidomics, respectively.

Our results showed that the BBR remarkably alleviated acute epileptic seizures and hippocampal neuron damage in KA-induced mice. The analysis of gut microbiota indicated that BBR reduced the acute epileptic seizures in KA-induced mice by increasing the abundance of Bacteroidetes and Alloprevotella, regulating short-chain fatty acids (SCFAs). Results of lipidomics also identified 21 candidate metabolites in the colon and hippocampus possibly involved in the protective effect of BBR against acute seizures.

These findings suggest that BBR exerts neuroprotection against KA-induced epileptic seizures through remodeling gut microbiota-associated lipid metabolism in the colon and hippocampus. BBR may serve as a valuable candidate drug for curing patients with epilepsy.

Background: Chronic stress and chronic pain are closely linked by the capacity to exacerbate each other, sharing common roots in the brain and in the gut. The strict intersection between these two neurological diseases makes important to have a therapeutic strategy aimed at preventing both to maintain mental health in patients. Diet is an modifiable lifestyle factor associated with gut-brain axis diseases and there is growing interest in its use as adjuvant to main therapies. Several evidence attest the impact of specific diets or nutrients on chronic stress-related disorders and pain with a good degree of certainty. A daily adequate intake of foods containing micronutrients such as amino acids, minerals and vitamins, as well as the reduction in the consumption of processed food products can have a positive impact on microbiota and gut health. Many nutrients are endowed of prebiotic, anti-inflammatory, immunomodulatory and neuroprotective potential which make them useful tools helping the management of chronic stress and pain in patients. Dietary regimes, as intermittent fasting or caloric restriction, are promising, although further studies are needed to optimize protocols according to patient's medical history, age and sex. Moreover, by supporting gut microbiota health with diet is possible to attenuate comorbidities such as obesity, gastrointestinal dysfunction and mood disorders, thus reducing healthcare costs related to chronic stress or pain.Objective: This review summarize the most recent evidence on the microbiota-mediated beneficial effects of macro- and micronutrients, dietary-related factors, specific nutritional regimens and dietary intervention on these pathological conditions.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and progressive neuronal damage. Recent research has highlighted the significant roles of the gut microbiota and microRNAs (miRNAs) in the pathogenesis of AD. This review explores the intricate interaction between gut microbiota and miRNAs, emphasizing their combined impact on Alzheimer's progression. First, we discuss the bidirectional communication within the gut-brain axis and how gut dysbiosis contributes to neuroinflammation and neurodegeneration in AD. Changes in gut microbiota composition in Alzheimer's patients have been linked to inflammation, which exacerbates disease progression. Next, we delve into the biology of miRNAs, focusing on their roles in gene regulation, neurodevelopment, and neurodegeneration. Dysregulated miRNAs are implicated in AD pathogenesis, influencing key processes like inflammation, tau pathology, and amyloid deposition. We then examine how the gut microbiota modulates miRNA expression, particularly in the brain, potentially altering neuroinflammatory responses and synaptic plasticity. The interplay between gut microbiota and miRNAs also affects blood-brain barrier integrity, further contributing to Alzheimer's pathology. Lastly, we explore therapeutic strategies targeting this gut microbiota-miRNA axis, including probiotics, prebiotics, and dietary interventions, aiming to modulate miRNA expression and improve AD outcomes. While promising, challenges remain in fully elucidating these interactions and translating them into effective therapies. This review highlights the importance of understanding the gut microbiota-miRNA relationship in AD, offering potential pathways for novel therapeutic approaches aimed at mitigating the disease's progression.