Gut microbiota preservation or rational manipulation is a key condition for healthy longevity and a promising strategy to prevent neurodegenerations exploiting the gut-brain axis, with a key role of prebiotics and probiotics. Whether their combination in a functional food can provide a synergistic effect to the host remains controversial. To fill this gap, we supplemented the diet of 3xTg-AD Alzheimer's disease mice with a red lentils (prebiotic)-based cookie enriched with neuroprotective probiotics and we performed behavioural, biochemical and molecular tests. Chronic consumption of this synbiotic preparation (functional cookie) preserved cognition, reduced amyloid load, improved glucose and lipid homeostasis and diminished oxidation and inflammation related damages compared to animals receiving a classic cookie (standard recipe). The synergistic effect was indicated by significantly higher glucose insulinotropic polypeptide concentrations in the functional cookie group compared to probiotic group. Moreover, Ruminoclostridium sp KB18 and Ruminicoccus decreased in the gut of mice supplemented with the functional cookie, partially explaining the improved short-term memory upon treatments and substantiating the combined use over individual components. This synbiotic innovative snack represents a prototype of a simple and affordable dietary approach to promote healthy aging and prevent or delay the onset of neurodegenerations.

To conduct an in-depth exploration of the specific impacts of probiotics and prebiotic supplements on cognitive impairment, it is imperative to also investigate pertinent factors, including the optimal dosage of probiotics for enhancing cognitive function. This investigation is essential for optimizing probiotic interventions to prevent and treat cognitive decline, aimed at preventing and aiding in the treatment of cognitive decline among patients with cognitive impairment.

A comprehensive computerized search was conducted across the Embase, PubMed, Web of Science, Cochrane Library, SinoMed, CNKI, Wanfang and WeiPu Data. Studies targeting randomized controlled trials (RCTs) were included. This search covered a timeframe extending from the inception of each database to September 2024. Following an independent process of literature screening, data extraction, and rigorous quality assessment conducted by two investigators, a meta-analysis was performed using Stata 15.0 software.

A total of ten studies, involving 778 patients, were included in the analysis. The meta-analysis revealed that probiotics were effective in enhancing cognitive function among patients with cognitive impairment, with a standardized mean difference (SMD) of 0.52 (95% CI: 0.07, 0.98; P < 0.001). Subgroup analysis further demonstrated that the largest effect size was observed for studies utilizing the Mini-Mental State Examination (MMSE) scale as the outcome measure (SMD = 0.88). Additionally, the greatest efficacy was associated with single-strain probiotics (SMD = 0.81), and interventions lasting ≤12 weeks exhibited the most pronounced effect (SMD = 0.61).

Probiotics have been shown to enhance cognitive function, with a probiotic intervention program featuring a single probiotic strain and a duration of ≤12 weeks demonstrating particularly robust efficacy in improving cognitive function, as assessed by the MMSE scale.

Alzheimer's disease (AD) has emerged as a global public health priority characterized by escalating prevalence and the limited efficacy of current therapeutic approaches. Although the pathological complexity of AD is well-recognized, its underlying etiology remains incompletely elucidated. Current research highlights a bidirectional gut-brain axis (GBA) interaction, wherein gut microbiome perturbations may impair intestinal barrier stability, influence immune responses, and blood-brain barrier permeability through microbial metabolite-mediated pathways, thereby contributing to AD pathophysiology. Notably, probiotics demonstrate therapeutic potential by restoring gut microbiome homeostasis, reinforcing intestinal barrier integrity, and mitigating neuroinflammatory responses via GBA. This review focuses on investigating the gut microbiome alterations in AD pathogenesis, the interaction of probiotics with GBA, and its significance in AD pathogenesis. By synthesizing current clinical evidence, this review aims to establish a scientific foundation for probiotic-based interventions as a novel therapeutic strategy in AD management.

Aging is associated with a decline in cognitive function and vulnerability to depression. Probiotic supplements have shown beneficial effects on cognition and mood in clinical populations, but the potential benefit for healthy older adults experiencing age-related decline in cognition remains unclear.

The primary aim of the present work was to explore the effect of a chronic (long-term) multispecies probiotic intervention on cognition in healthy aging adults. Secondary aims included exploring the chronic effect on mood outcomes and gut microbiota community, as well as a novel investigation into the acute effect of supplementation on cognition and mood.

The study employed a randomized, placebo-controlled, cross-over trial in 30 healthy older adults to explore the acute (1 d) and chronic (8 wk) effects of a probiotic supplement on cognitive domains of memory and executive function, alongside mood measures of stress, anxiety, depression, and cognitive reactivity to sad mood. 16s rRNA sequencing of stool samples was also performed pre- and postchronic intervention to assess potential effects on the gut microbiota.

Acute probiotic supplementation was associated with faster reaction times on cognitively demanding trials during a task of executive function [-64.91 ms, 95% confidence interval (CI): -115.70, -14.15]. Chronic supplementation was associated with improvement in cognitive biases such as hopelessness (-0.97, 95% CI: -1.72, -0.23), rumination (-1.58, 95% CI: -2.86, -0.29), and aggression (-1.57, 95% CI: -2.63, -0.51) that contribute to reactivity to sad mood and therefore vulnerability to depression, and may improve executive function under higher cognitive demand (0.43%, 95% CI: -0.53%, 1.38%).

The current work provides novel evidence for an acute effect of probiotics on reaction times during executive function, which should be replicated in future work. Additionally, this work replicates previous findings of improved cognitive reactivity to sad mood following chronic probiotic supplementation, indicating probiotics may reduce risk of developing depression in a healthy aging population. This study was registered at clinicaltrials.gov as NCT04951687.

Alzheimer's disease (AD) is a progressive neurodegenerative disease, characterized by oxidative stress, neuroinflammation, mitochondrial dysfunction, neurotransmitter imbalance, tau hyperphosphorylation, and amyloid beta (Aβ) accumulation in brain regions. The gut microbiota (GM) has a major impact on brain function due to its bidirectional interaction with the gut through the gut-brain axis. The gut dysbiosis has been associated with neurological disorders, emphasizing the importance of gut homeostasis in maintaining appropriate brain function. The changes in the composition of microbiomes influence neuroinflammation and Aβ accumulation by releasing pro-inflammatory cytokines, decreasing gut and blood-brain barrier (BBB) integrity, and microglial activation in the brain. Postbiotics, are bioactive compounds produced after fermentation, have been shown to provide several health benefits, particularly in terms of neuroinflammation and cognitive alterations associated with AD. Several research studies on animal models and human have successfully proven the effects of postbiotics on enhancing cognition and memory in experimental animals. This article explores the protective effects of postbiotics on cellular mechanisms responsible for AD pathogenesis and studies highlighting the influence of postbiotics as a total combination and specific compounds, including short-chain fatty acids (SCFAs). In addition, postbiotics act as a promising option for future research to deal with AD's progressive nature and improve an individual's life quality using microbiota modulation.

Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), arise from complex interactions between genetic factors, environmental exposures, and aging. Additionally, gut dysbiosis has been linked to systemic inflammation and neurodegeneration. Advances in microbiome and metabolome profiling techniques have provided deeper insights into how alterations in gut microbiota and dietary patterns affect metabolic pathways and contribute to the progression of NDs. This review explores the profiles of gut microbiome and metabolome derived biomarkers and their roles in NDs. Across phyla, families, and genera, we identified 55 microbial alterations in PD, 24 in AD, 4 in ALS, and 17 in MS. Some notable results include an increase in Akkermansia in PD, AD, and MS and a decrease in short-chain fatty acids (SCFAs) in PD and AD. We examined the effects of probiotics, prebiotics, fecal microbiota transplants (FMT), sleep, exercise, and diet on the microbiota, all of which contributed to delayed onset and alleviation of symptoms. Further, artificial intelligence (AI) and machine learning (ML) algorithms applied to omics data have been crucial in identifying novel therapeutic targets, diagnosing and predicting prognosis, and enabling personalized medicine using microbiota-modulating therapies in NDs patients.

Metabolic syndrome (MetS) and mild cognitive impairment (MCI) are interconnected conditions sharing common pathological pathways, such as inflammation and oxidative stress, leading to the concept of "metabolic-cognitive syndrome." This highlights their mutual influence and potential overlapping therapeutic strategies. Although lifestyle modifications remain essential, nutraceutical supplementation has emerged as a promising adjunct for the prevention and management of these preclinical conditions. This review examines clinical and translational evidence on commonly used nutraceuticals targeting shared pathophysiological mechanisms of MetS and MCI. By addressing inflammation, oxidative stress, and metabolic dysfunction, these supplements may offer a valuable approach to mitigating the progression and consequences of both conditions. Understanding their efficacy could provide practical tools to complement lifestyle changes, offering a more comprehensive strategy for managing metabolic-cognitive syndrome.

Alzheimer's disease (AD) is the most common form of dementia and is characterized by memory impairment that significantly interferes with daily life. Therapeutic options for AD that substantively modify disease progression remain a critical unmet need. In this regard, the gut microbiota is crucial in maintaining human health by regulating metabolism and immune responses, and increasing evidence suggests that probiotics, particularly beneficial bacteria, can enhance memory and cognitive functions. Recent studies have highlighted the positive effects of Bifidobacterium breve MCC1274 (B. breve MCC1274) on individuals with mild cognitive impairment (MCI) and schizophrenia. Additionally, oral supplementation with B. breve MCC1274 has been shown to effectively prevent memory decline in AppNL-G-F mice. In relation to Alzheimer's pathology, oral supplementation with B. breve MCC1274 has been found to reduce amyloid-β (Aβ) accumulation and tau phosphorylation in both AppNL-G-F and wild-type (WT) mice. It also decreases microglial activation and increases levels of synaptic proteins. In this review, we examine the beneficial effects of B. breve MCC1274 on AD, exploring potential mechanisms of action and how this probiotic strain may aid in preventing or treating the disease. Furthermore, we discuss the broader implications of B. breve MCC1274 for improving overall host health and provide insights into future research directions for this promising probiotic therapy.

Background/Objectives: This systematic review focused on collecting the most significant findings on the impact of the administration of Bifidobacterium infantis (or Bifidobacterium longum subps. infantis) and Bifidobacterium breve, alone, in conjunction, or in combination with other strains, in the treatment of neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). These diseases are characterized by the progressive degeneration of neurons, resulting in a broad spectrum of clinical manifestations. AD is typified by a progressive decline in cognitive abilities, while PD is marked by motor symptoms associated with the loss of dopamine (DA). Methods: Five different databases, ScienceDirect, Scopus, Wiley, PubMed, and Web of Science (WoS), were reviewed and the studies were screened for inclusion by the following criteria: (i) studies that specifically evaluated the use of Bifidobacterium infantis, Bifidobacterium longum subsp. infantis, or Bifidobacterium breve as a therapeutic intervention, either in human or animal models, in the context of neurodegenerative diseases; (ii) the studies were required to address one or more of the pathologies examined in this article, and the pathologies included, but were not limited to, neurodegeneration, Alzheimer's disease, Parkinson's disease, and oxidative stress; (iii) the full text was accessible online; and (iv) the article was written in English. Results: The data suggest that these probiotics have neuroprotective effects that may delay disease progression. Conclusions: This study provides updated insights into the use of these Bifidobacterium strains in neurodegenerative diseases like AD and PD, with the main limitation being the limited number of clinical trials available.

Neurodegenerative diseases (NDDs), characterized by the progressive deterioration of the structure and function of the nervous system, represent a significant global health challenge. Emerging research suggests that the gut microbiota plays a critical role in regulating neurodegeneration via modulation of the gut-brain axis. Probiotics, defined as live microorganisms that confer health benefits to the host, have garnered significant attention owing to their therapeutic potential in NDDs. This review examines the current research trends related to the microbiome-gut-brain axis across various NDDs, highlighting key findings and their implications. Additionally, the effects of specific probiotic strains, including Lactobacillus plantarum, Bifidobacterium breve, and Lactobacillus rhamnosus, on neurodegenerative processes were assessed, focusing on their potential therapeutic benefits. Overall, this review emphasizes the potential of probiotics as promising therapeutic agents for NDDs, underscoring the importance of further investigation into this emerging field.

With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut-brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut-brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with its prevalence doubling approximately every decade. It is a significant contributor to disability-adjusted life-years in individuals aged 50 and older, impacting a substantial portion of this population globally. The pathophysiology of AD is primarily explained by two hypotheses: the amyloid cascade hypothesis and the tau hypothesis. While the amyloid cascade hypothesis is widely accepted as the main contributor to AD, both mechanisms promote neuroinflammation by driving the formation of amyloid-beta (Aβ) plaques and tau tangles, which are key features of the neurodegenerative process. Recent studies highlight the critical role of the gut microbiome (GMB) in the progression of AD. Gut dysbiosis has been linked to neuroinflammation, altered Aβ metabolism, blood-brain barrier disruption, and changes in neuroactive metabolites. Targeting the GMB offers potential therapeutic avenues aimed at restoring microbial balance and mitigating the effects of dysbiosis. The gut-brain axis, crucial for neurological health, remains underexplored in AD, especially since current research is limited to animal models and small human studies, leaving uncertainty about specific gut bacteria's roles in AD. Currently, pharmacological treatments for AD include cholinesterase inhibitors and memantine. This review discusses newer and emerging treatments targeting Aβ and tau pathology, alongside microbiome-based interventions. Larger, human-based studies with diverse populations are essential to establish the therapeutic efficacy of these microbiome-targeted treatments and their long-term impact on AD management.

The prevalence of obesity in dogs is increasing worldwide. This study evaluated the effects of a mixed probiotic formula on the weight, body condition score (BCS), blood metabolite profiles, and gut microbiota of overweight and obese dogs over a 12-week supplementation period to determine the anti-obesity effects of Lactiplantibacillus plantarum CBT LP3 and Bifidobacterium breve CBT BR3. This was a community-based, randomized study that sampled 41 overweight and obese dogs with a veterinarian-determined BCS of 6 or more. The physical activity of all the subjects was measured using a pedometer designed exclusively for dogs. The food intake was measured using the developed application. Only the treatment group received the mixed probiotic formula twice daily (3 g per dose). A significant decrease in body weight (p < 0.0001), BCS (p < 0.0001), serum TG (p < 0.0001), serum TC (p = 0.0400), and serum leptin (p = 0.0252), and a significantly increased serum adiponectin levels (p = 0.0007) were observed in the treatment group compared with the values in the control group. Microbiota analysis showed that Lactiplantibacillus increased and Erysipelatoclostridium, Staphylococcus, and Gemella decreased more significantly in the treatment group than in the control group. These results suggested that Lactiplantibacillus plantarum CBT LP3 and Bifidobacterium breve CBT BR3 may be effective in alleviating obesity in dogs.

Mild cognitive impairment (MCI) and Alzheimer's disease (AD) are progressive neurodegenerative disorders, and probiotics may offer therapeutic benefits by modulating gut microbiota and reducing inflammation.

This study systematically evaluated the impact of probiotics on cognitive function in MCI and AD through a meta-analysis of randomized controlled trials (RCTs).

A systematic review and meta-analysis were performed following PRISMA 2020 guidelines. PubMed, Embase, EBSCO, and Cochrane databases were searched for RCTs (January 2000-January 2024) on probiotic interventions lasting 8-24 weeks. Cognitive outcomes included Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), language, naming, visual-spatial, memory, and attention. Data were analyzed using R with a random-effects model to calculate pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). Risk of bias was rigorously assessed.

Out of 2000 articles, 500 full texts were screened, and 10 studies were included. The meta-analysis showed varied effect sizes: MMSE (SMD: 0.28, 95%CI -0.35-0.91, p = 0.38), MoCA (SMD: 0.51, 95%CI -0.49-1.52, p = 0.33), language (SMD: -0.12, 95% CI -0.54-0.29, p = 0.56), naming (SMD: 0.02, 95%CI -0.69-0.74, p = 0.95), visual-spatial (SMD: 0.38, 95%CI -0.13-0.88, p = 0.14), memory (SMD: 0.20, 95%CI -0.15-0.55, p = 0.26), and attention (SMD: -0.07, 95%CI -0.44-0.30, p = 0.71). Positive SMDs suggest cognitive improvement, while non-significant negative SMDs indicate trends toward decline, inclined by probiotic strains, duration, and participant characteristics.

Probiotics did not significantly improve cognitive function in MCI and AD patients, with variability in effects across cognitive domains, suggesting the need for tailored interventions and future studies.

Gut microbiota changes and brain-gut-axis (BGA) dysregulation are common in people with Parkinson's Disease (PD). Probiotics and prebiotics are emerging as a potential therapeutic approach for PD patients. The aim of this paper was to assess the neurological and gastroenterological effects in PD patients with constipation after the administration of a synbiotic product, with a focus on behavioral and cognitive symptoms. We enrolled patients with stable PD who met diagnostic criteria for functional constipation and/or irritable bowel syndrome with constipation according to Rome IV Criteria. Patients received a synbiotic treatment (Enterolactis Duo, containing the probiotic strain Lacticaseibacillus paracasei DG and the prebiotic fiber inulin) for 12 weeks. A neurological and a gastroenterological evaluation were collected before and after the treatment. In addition, 16S rRNA gene profiling and short chain fatty acid quantification were performed to characterize the microbial ecosystem of fecal samples collected before (n = 22) and after (n = 9) the synbiotic administration. 30 patients were consecutively enrolled. After treatment, patients performed better in MDS-UPDRS part 1 (p = 0.000), SCOPA-AUT (p = 0.001), TAS-20 (p = 0.014), HAM-D (p = 0.026), DIFt (p = 0.003), PAS-A (p = 0.048). Gastroenterological evaluations showed improvements in PAC-SYM score (p < 0.001), number of complete bowel movement (p < 0.001) and BSFS (p < 0.001). After the synbiotic administration, we observed a significant increase in the abundance of the order Oscillospirales, as well as the Oscillospiraceae family and the species Faecalibacterium prausnitzii within this order in fecal samples. Synbiotic treatment demonstrates potential efficacy in ameliorating non-motor features in PD patients.

The complex network of factors that contribute to neurodegeneration have hampered the discovery of effective preventative measures. While much work has focused on brain-first therapeutics, it is becoming evident that physiological changes outside of the brain are the best target for early interventions. Specifically, myeloid cells, including peripheral macrophages and microglia, are a sensitive population of cells whose activity can directly impact neuronal health. Myeloid cell activity includes cytokine production, migration, debris clearance, and phagocytosis. Environmental measures that can modulate these activities range from toxin exposure to diet. However, one of the most influential mediators of myeloid fitness is the gut microenvironment. Here, we review the current data about the role of myeloid cells in gastrointestinal disorders, Parkinson's disease, dementia, and multiple sclerosis. We then delve into the gut microbiota modulating therapies available and clinical evidence for their use in neurodegeneration. Modulating lifestyle and environmental mediators of inflammation are one of the most promising interventions for neurodegeneration and a systematic and concerted effort to examine these factors in healthy aging is the next frontier.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

Alzheimer's disease (AD) is a progressive neurological disorder that represents a major cause of dementia worldwide. Its pathogenesis involves multiple pathways, including the amyloid cascade, tau protein, oxidative stress, and metal ion dysregulation. Recent studies have suggested a critical link between changes in gut microbial diversity and the disruption of the gut-brain axis in AD. Previous studies primarily explored the potential benefits of probiotics and prebiotics in managing AD. However, studies have yet to fully describe a novel promising approach involving the use of synbiotics, which include a combination of active probiotics and new-generation prebiotics. Synbiotics show potential for mitigating the onset and progression of AD, thereby offering a holistic approach to address the multifaceted nature of AD. This review article primarily aims to gain further insights into the mechanisms of AD, specifically the intricate interaction between gut bacteria and the brain via the gut-brain axis. By understanding this relationship, we can identify potential targets for intervention and therapeutic strategies to combat AD effectively. This review also discusses substantial evidence supporting the role of synbiotics as a promising AD treatment that surpasses traditional probiotic or prebiotic interventions. We find that synbiotics may be used not only to address cognitive decline but also to reduce AD-related psychological burden, thus enhancing the overall quality of life of patients with AD.

The gut microbiome plays a crucial role in host health throughout the lifespan by influencing brain function during aging. The microbial diversity of the human gut microbiome decreases during the aging process and, as a consequence, several mechanisms increase, such as oxidative stress, mitochondrial dysfunction, inflammatory response, and microbial gut dysbiosis. Moreover, evidence indicates that aging and neurodegeneration are closely related; consequently, the gut microbiome may serve as a novel marker of lifespan in the elderly. In this narrative study, we investigated how the changes in the composition of the gut microbiome that occur in aging influence to various neuropathological disorders, such as mild cognitive impairment (MCI), dementia, Alzheimer's disease (AD), and Parkinson's disease (PD); and which are the possible mechanisms that govern the relationship between the gut microbiome and cognitive impairment. In addition, several studies suggest that the gut microbiome may be a potential novel target to improve hallmarks of brain aging and to promote healthy cognition; therefore, current and future therapeutic interventions have been also reviewed.

Recently, more consumers are interested in purchasing probiotic food and beverage products that may improve their immune health. The market for functional foods and beverages that include Bifidobacterium is expanding because of their potential uses in both food and therapeutic applications. However, maintaining Bifidobacterium's viability during food processing and storage remains a challenge. Microencapsulation technique has been explored to improve the viability of Bifidobacterium. Despite the technical, microbiological, and economic challenges, the market potential for immune-supporting functional foods and beverages is significant. Additionally, there is a shift toward postbiotics as a solution for product innovation, a promising postbiotic product that can be incorporated into various food and beverage formats is also introduced in this review. As consumers become more health-conscious, future developments in the functional food and beverage market discussed in this review could serve as a reference for researchers and industrialist.

Alzheimer's disease, among the most common neurodegenerative disorders, is characterized by progressive cognitive impairment. At present, the Alzheimer's disease main risk remains genetic risks, but major environmental factors are increasingly shown to impact Alzheimer's disease development and progression. Microglia, the most important brain immune cells, play a central role in Alzheimer's disease pathogenesis and are considered environmental and lifestyle "sensors." Factors like environmental pollution and modern lifestyles (e.g., chronic stress, poor dietary habits, sleep, and circadian rhythm disorders) can cause neuroinflammatory responses that lead to cognitive impairment via microglial functioning and phenotypic regulation. However, the specific mechanisms underlying interactions among these factors and microglia in Alzheimer's disease are unclear. Herein, we: discuss the biological effects of air pollution, chronic stress, gut microbiota, sleep patterns, physical exercise, cigarette smoking, and caffeine consumption on microglia; consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer's disease; and present the neuroprotective effects of a healthy lifestyle. Toward intervening and controlling these environmental risk factors at an early Alzheimer's disease stage, understanding the role of microglia in Alzheimer's disease development, and targeting strategies to target microglia, could be essential to future Alzheimer's disease treatments.

Over the past decades, accumulating evidence suggests that the gut microbiome exerts a key role in Alzheimer's disease (AD). The Alzheimer's Association Workgroup is updating the diagnostic criteria for AD, which changed the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." Previously, most of studies focus on the correlation between the gut microbiome and amyloid beta deposition ("A"), the initial AD pathological feature triggering the "downstream" tauopathy and neurodegeneration. However, limited research investigated the interactions between the gut microbiome and other AD pathogenesis ("TNIVS"). In this review, we summarize current findings of the gut microbial characteristics in the whole spectrum of AD. Then, we describe the association of the gut microbiome with updated biomarker categories of AD pathogenesis. In addition, we outline the gut microbiome-related therapeutic strategies for AD. Finally, we discuss current key issues of the gut microbiome research in the AD field and future research directions. HIGHLIGHTS: The new revised criteria for Alzheimer's disease (AD) proposed by the Alzheimer's Association Workgroup have updated the profiles and categorization of biomarkers from "AT(N)" to "ATNIVS." The associations of the gut microbiome with updated biomarker categories of AD pathogenesis are described. Current findings of the gut microbial characteristics in the whole spectrum of AD are summarized. Therapeutic strategies for AD based on the gut microbiome are proposed.

Recent clinical studies have yielded controversial results regarding the effect of probiotics on cognitive function in Alzheimer's disease (AD) or mild cognitive impairment (MCI) subjects. To clarify the efficacy of probiotics on cognition, we conducted a meta-analysis of randomized controlled trials (RCTs).

Instructions of the PRISMA 2020 statement were followed. Literature from the PubMed, Embase and Cochrane databases were systematically searched and manually screened for relevant published RCTs. We performed statistical analysis using RevMan, and assessed the risk of bias using the R software.

A total of 12 studies comprising 852 patients with MCI or AD were identified. The results of meta-analysis showed that probiotics improved global cognitive function (SMD=0.67; 95% CI, 0.32, 1.02), recall/delayed memory (SMD=0.67; 95% CI: 0.32, 1.02), attention (SMD=0.31; 95% CI: 0.04, 0.58) and visuospatial/constructional (SMD=0.24; 95% CI: 0.06, 0.42) cognitive domain.

This meta-analysis found that probiotic supplementation is associated with an improvement in cognitive performance among patients with AD and MCI. However, current evidence is limited, and more reliable large-scale RCTs with higher methodological quality are needed.

Mild cognitive impairment (MCI) is a heterogeneous condition definable as the intermediate clinical state between normal aging and dementia. As a pre-dementia condition, there is a recent growing interest in the identification of non-invasive markers able to predict the progression from MCI to a more advanced stage of the disease. Previous evidence showed the close link between gut microbiota and neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). Conversely, the actual relationship between gut microbiota and MCI is yet to be clarified. In this work, we provide an overview about the current knowledge regarding the role of gut microbiota in the context of MCI, also assessing the potential for microbiota-targeted therapies. Through the review of the most recent studies focusing on this topic, we found evidence of an increase of Bacteroidetes at phylum level and Bacteroides at genus level in MCI subjects with respect to healthy controls and patients with AD. Despite such initial evidence, the definitive identification of a typical microbiota profile associated with MCI is still far from being achieved. These preliminary results, however, are growingly encouraging research on the role of gut microbiota modulation in improving the cognitive status of pre-dementia subjects. To date, few studies evaluated the role of probiotics in MCI subjects, and they showed favorable results, although still biased by small sample size, heterogeneity of study design and short follow-up.

In this study, a systematic review of randomized clinical trials conducted from January 2000 to December 2023 was performed to examine the efficacy of psychobiotics-probiotics beneficial to mental health via the gut-brain axis-in adults with psychiatric and cognitive disorders. Out of the 51 studies involving 3353 patients where half received psychobiotics, there was a notably high measurement of effectiveness specifically in the treatment of depression symptoms. Most participants were older and female, with treatments commonly utilizing strains of Lactobacillus and Bifidobacteria over periods ranging from 4 to 24 weeks. Although there was a general agreement on the effectiveness of psychobiotics, the variability in treatment approaches and clinical presentations limits the comparability and generalization of the findings. This underscores the need for more personalized treatment optimization and a deeper investigation into the mechanisms through which psychobiotics act. The research corroborates the therapeutic potential of psychobiotics and represents progress in the management of psychiatric and cognitive disorders.

Recent research exploring the relationship between the gut and the brain suggests that the condition of the gut microbiota can influence cognitive health. A well-balanced gut microbiota may help reduce inflammation, which is linked to neurodegenerative conditions. Prebiotics, probiotics, and symbiotics are nutritional supplements and functional food components associated with gastrointestinal well-being. The bidirectional communication of the gut-brain axis is essential for maintaining homeostasis, with pre-, pro-, and symbiotics potentially affecting various cognitive functions such as attention, perception, and memory. Numerous studies have consistently shown that incorporating pre-, pro-, and symbiotics into a healthy diet can lead to improvements in cognitive functions and mood. Maintaining a healthy gut microbiota can support optimal cognitive function, which is crucial for disease prevention in our fast-paced, Westernized society. Our results indicate cognitive benefits in healthy older individuals with probiotic supplementation but not in healthy older individuals who have good and adequate levels of physical activity. Additionally, it appears that there are cognitive benefits in patients with mild cognitive impairment and Alzheimer's disease, while mixed results seem to arise in younger and healthier individuals. However, it is important to acknowledge that individual responses may vary, and the use of these dietary supplements should be tailored to each individual's unique health circumstances and needs.

Alzheimer's disease, one of the most severe and common neurodegenerative diseases, has no effective cure. Therefore it is crucial to explore novel and effective therapeutic targets. The gut microbiota - brain axis has been found to play a role in Alzheimer's disease by regulating the neuro-immune and endocrine systems. At the same time, acupuncture can modulate the gut microbiota and may impact the course of Alzheimer's disease. In this Review, we discuss recent studies on the role of acupuncture on the gut microbiota as well current challenges and future opportunities of acupuncture as potential treatment for the prevention and treatment of Alzheimer's disease.

This work explored the effects of Lactobacillus plantarum LLY-606 (LLY-606) on cognitive function in aging mice. Our findings demonstrated that LLY-606 effectively prolonged the lifespan of mice and improved age-related cognitive impairments. Additionally, our study revealed that supplementation with LLY-606 resulted in the downregulation of inflammatory cytokine levels and the upregulation of antioxidant capacity. Furthermore, probiotic supplementation effectively mitigated the deterioration of the intestinal barrier function in aging mice. Amplicon analysis indicated the successful colonization of probiotics, facilitating the regulation of age-induced gut microbiota dysbiosis. Notably, the functional abundance prediction of microbiota indicated that tryptophan metabolism pathways, glutamatergic synapse pathways, propanoate metabolism pathways, and arginine and proline metabolism pathways were enriched after the LLY-606 intervention. In summary, LLY-606 emerged as a potential functional probiotic capable of influencing cognitive function in aging mice. This effect was achieved through the modulation of gut microbiota, the regulation of synaptic plasticity, and the enhancement of neurotrophic factor levels.

The human gastrointestinal tract is populated with a diverse microbial community. The vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect of human biology, including health maintenance, development, aging, and disease. The advent of new sequencing technologies and culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations to shed light on microbiome-host interactions. Evidence has unveiled the bidirectional communication between the gut microbiome and the central nervous system, referred to as the "microbiota-gut-brain axis". The microbiota-gut-brain axis represents an important regulator of glial functions, making it an actionable target to ameliorate the development and progression of neurodegenerative diseases. In this review, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases. As the gut microbiome provides essential cues to microglia, astrocytes, and oligodendrocytes, we examine the communications between gut microbiota and these glial cells during healthy states and neurodegenerative diseases. Subsequently, we discuss the mechanisms of the microbiota-gut-brain axis in neurodegenerative diseases using a metabolite-centric approach, while also examining the role of gut microbiota-related neurotransmitters and gut hormones. Next, we examine the potential of targeting the intestinal barrier, blood-brain barrier, meninges, and peripheral immune system to counteract glial dysfunction in neurodegeneration. Finally, we conclude by assessing the pre-clinical and clinical evidence of probiotics, prebiotics, and fecal microbiota transplantation in neurodegenerative diseases. A thorough comprehension of the microbiota-gut-brain axis will foster the development of effective therapeutic interventions for the management of neurodegenerative diseases.

Alzheimer's disease is a progressive neurodegenerative disorder with a complex etiology, and effective interventions to prevent or delay its onset remain a global health challenge. In recent years, there has been growing interest in the potential role of probiotic and vitamin supplementation as complementary strategies for Alzheimer's disease prevention. This review paper explores the current scientific literature on the use of probiotics and vitamins, particularly vitamin A, D, E, K, and B-complex vitamins, in the context of Alzheimer's disease prevention and management. We delve into the mechanisms through which probiotics may modulate gut-brain interactions and neuroinflammation while vitamins play crucial roles in neuronal health and cognitive function. The paper also examines the collective impact of this combinational therapy on reducing the risk factors associated with Alzheimer's disease, such as oxidative stress, inflammation, and gut dysbiosis. By providing a comprehensive overview of the existing evidence and potential mechanisms, this review aims to shed light on the promise of probiotic and vitamin co-supplementation as a multifaceted approach to combat Alzheimer's disease, offering insights into possible avenues for future research and clinical application.

To explore gut microbiota changes in intractable epilepsy patients compared to healthy control individuals through meta-analysis.

PubMed, Web of Science, CNKI, Wanfang, medRxiv, bioRxiv, ilae.org, clinical trial databases, and papers from the International Epilepsy Congress (IEC) were searched, and the literature on the correlation between intractable epilepsy and the gut microbiota reported from database establishment to June 2023 was included. Literature meeting the inclusion criteria was screened, and meta-analysis of the included literature was performed using RevMan5.4 software.

Ten case-control studies were included in the meta-analysis. There were 183 patients with intractable epilepsy and 283 healthy control subjects. The analysis results indicated that Bacteroidetes (MD = -0.64, 95 %-CI = -1.21 to -0.06) and Ruminococcaceae (MD = -1.44, 95 % CI = -1.96 to -0.92) were less abundant in the patients with intractable epilepsy than in the normal population. Proteobacteria (MD = 0.53, 95 % CI = 0.02 to 1.05) and Verrucomicrobia (MD = 0.26, 95 % CI = 0.06 to 0.45) were more abundant in the patients with intractable epilepsy than in the normal population.

This meta-analysis indicated that the abundances of Bacteroidetes and Ruminococcaceae were reduced while those of Proteobacteria and Verrucomicrobia were significantly increased in patients with intractable epilepsy. The above changes in these four taxa of the gut microbiota may have been induced by intractable epilepsy, which may increase the risk of seizures. Their roles in the pathogenesis of intractable epilepsy need to be further explored, and related factors that influence microbiota changes should be considered in future studies.

Given that there is already evidence of a neural network that connects the brain and gut and that the gut microbiota actively modulates gut health, it is crucial to know which foods, supplements, and medications to use or avoid when treating any disease that causes dementia or cognitive impairment. Previous research has examined the relationships between vitamins, antibiotics, and gut microbiota and the correlations between these factors and dementia. The question arises of how these three factors interact together and if evidence suggests one element is more important than the others in the pathogenesis and development of dementia.

The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards were followed when conducting this review. The papers' publication dates varied from (2012-2022). Cochrane/EMBASE, PEDro, and PubMed/Medline databases were searched. The precise terms "gut microbiota," vitamins," antibiotics," and "dementia" were included in the search method, along with the conjunctions "OR" and "AND."

Gut dysbiosis has a significant impact on cognition, brain function, and the development and progression of dementia. The two most popular probiotics used in studies linked to cognition benefits were Lactobacillus and Bifidobacterium. Numerous scales were used to evaluate cognition, but the mini-mental state examination was the most popular, and the most prevalent impairment was Alzheimer's disease. The supplements with the most significant impact on gut microbiota were vitamin B-12 and folic acid.

This systematic review concluded that vitamins, gut microbiota and antibiotics have a close association with the development of dementia. More research is required to establish causality and elucidate the underlying mechanisms because there is still little evidence connecting the interactions of vitamins, medications, and microbiota with dementia. The complexity of interactions between genetics, lifestyle factors, and comorbidities, as well as the heterogeneity of dementia, may make it more challenging to interpret the findings.

Recent advances linking gut dysbiosis with neurocognitive disorders such as Alzheimer's disease (AD) suggest that the microbiota-gut-brain axis could be targeted for AD prevention, management, or treatment.

We sought to identify probiotics that can delay Aβ-induced paralysis.

Using C. elegans expressing human amyloid-β (Aβ)1-42 in body wall muscles (GMC101), we assessed the effects of several probiotic strains on paralysis.

We found that Lacticaseibacillus rhamnosus HA-114 and Bacillus subtilis R0179, but not their supernatants or heat-treated forms, delayed paralysis and prolonged lifespan without affecting the levels of amyloid-β aggregates. To uncover the mechanism involved, we explored the role of two known pathways involved in neurogenerative diseases, namely mitophagy, via deletion of the mitophagy factor PINK-1, and fatty acid desaturation, via deletion of the Δ9 desaturase FAT-5. Pink-1 deletion in GMC101 worms did not modify the life-prolonging and anti-paralysis effects of HA-114 but reduced the protective effect of R0179 against paralysis without affecting its life-prolonging effect. Upon fat5 deletion in GMC101 worms, the monounsaturated C14:1 and C16:1 FAs conserved their beneficial effect while the saturated C14:0 and C16:0 FAs did not. The beneficial effects of R0179 on both lifespan and paralysis remained unaffected by fat-5 deletion, while the beneficial effect of HA-114 on paralysis and lifespan was significantly reduced.

Collectively with clinical and preclinical evidence in other models, our results suggest that HA-114 or R0179 could be studied as potential therapeutical adjuncts in neurodegenerative diseases such as AD.

Increased longevity is often associated with age-related conditions. The most common neurodegenerative disorders in the older population are Alzheimer's disease (AD) and Parkinson's disease (PD), associated with progressive neuronal loss leading to functional and cognitive impairments. Although symptomatic treatments are available, there is currently no cure for these conditions. Gut dysbiosis has been involved in the pathogenesis of AD and PD, thus interventions targeting the "gut-brain axis" could potentially prevent or delay these pathologies. Recent evidence suggests that the skeletal muscle and the gut microbiota can affect each other via the "gut-muscle axis". Importantly, cognitive functions in AD and PD patients significantly benefit from physical activity. In this review, we aim to provide a comprehensive picture of the crosstalk between the brain, the skeletal muscle and the gut microbiota, introducing the concept of "gut-muscle-brain axis". Moreover, we discuss human and animal studies exploring the modulatory role of exercise and probiotics on cognition in AD and PD. Collectively, the findings presented here support the potential benefits of physical activity and probiotic supplementation in AD and PD. Further studies will be needed to develop targeted and multimodal strategies, including lifestyle changes, to prevent or delay the course of these pathologies.

The advent of high-throughput 'omics' technologies has improved our knowledge of gut microbiome in human health and disease, including Alzheimer's disease (AD), a neurodegenerative disorder. Frequent bidirectional communications and mutual regulation exist between the gastrointestinal tract and the central nervous system through the gut-brain axis. A large body of research has reported a close association between the gut microbiota and AD development, and restoring a healthy gut microbiota may curb or even improve AD symptoms and progression. Thus, modulation of the gut microbiota has become a novel paradigm for clinical management of AD, and emerging effort has focused on developing potential novel strategies for preventing and/or treating the disease. In this review, we provide an overview of the connection and causal relationship between gut dysbiosis and AD, the mechanisms of gut microbiota in driving AD progression, and the successes and challenges of implementing available gut microbiome-targeted therapies (including probiotics, prebiotics, synbiotics, postbiotics, and fecal microbiota transplantation) in preventive and/or therapeutic preclinical and clinical intervention studies of AD. Finally, we discuss the future directions in this field.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by dementia and the accumulation of amyloid beta in the brain. Recently, microbial dysbiosis has been identified as one of the major factors involved in the onset and progression of AD. Imbalance in gut microbiota is known to affect central nervous system (CNS) functions through the gut-brain axis and involves inflammatory, immune, neuroendocrine and metabolic pathways. An altered gut microbiome is known to affect the gut and BBB permeability, resulting in imbalance in levels of neurotransmitters and neuroactive peptides/factors. Restoration of levels of beneficial microorganisms in the gut has demonstrated promising effects in AD in pre-clinical and clinical studies. The current review enlists the important beneficial microbial species present in the gut, the effect of their metabolites on CNS, mechanisms involved in dysbiosis related to AD and the beneficial effects of probiotics on AD. It also highlights challenges involved in large-scale manufacturing and quality control of probiotic formulations.

This study aimed to evaluate the improvement of cognitive impairment in older adults through probiotic supplementation.

A literature review on probiotic supplementation for treating cognitive impairment in older adults was conducted using English and Chinese databases from 1984 to 2023. Two researchers extracted relevant data independently, and a meta-analysis was performed with RevMan software.

A comprehensive analysis of ten pertinent papers was conducted, involving a sample of 702 old adults with cognitive impairment. The findings from this study revealed that probiotic supplementation exhibited a positive impact on cognitive symptoms, specifically memory (MD = 0.14, 95% CI :0.05～0.22, P = 0.001) and overall cognitive function (SMD = 0.73, 95% CI: 0.25～1.21, P=0.003), as well as oxidative stress levels, including total antioxidant capacity (MD=52.54, 95% CI:39.52～65.56, P < 0.01), malondialdehyde (MD=-0.11, 95% CI:-0.15～-0.07, P < 0.01), and glutathione (MD=17.08, 95% CI:8.65～25.5, P < 0.01). However, probiotic supplementation failed to enhance patients' psychological symptoms (SMD =0.18, 95% CI:-0.56～0.92, P = 0.64).

Probiotic supplementation can enhance cognitive symptoms and decrease oxidative stress in older adults with cognitive impairment. However, it does not improve psychological symptoms. More research is needed to determine the effects of probiotic supplementation on gastrointestinal symptoms and sleep quality in this population. Further supplementation and improvement will be necessary once high-quality literature becomes available.

Cognitive function is a significant concern among the elderly and has a major negative effect on their quality of life. Probiotics have a positive effect on improving cognition, but the exact nature of the association between probiotic supplements and cognitive function is poorly understood.

The purpose of this systematic review was to evaluate how probiotic supplements improve cognitive function.

A systematic search was conducted of the PubMed, Web of Science, the Cochrane Library, Embase, and ClinicalTrials.gov databases for all relevant studies published in English, with no date restrictions.

The estimated, pooled results were analyzed with a standardized mean difference (SMD) and a corresponding 95% confidence interval (95%CI). Publication bias was analyzed by the Egger's and Begg's tests. Funnel plots were also constructed to assess the probability of publication bias. The robustness of the results was tested using the method of sequential removal and cumulation of each trial.

Overall, the pooled SMD showed significant differences between the probiotic and placebo groups (SMD = 0.64; 95%CI, 0.15-1.12), with significant heterogeneity (I2 = 92%). Subgroup analyses showed a significant effect of probiotics on cognition in the studies involving populations with Alzheimer's disease and cognitive impairment (SMD = 1.34; 95%CI, 0.51-2.16; P < 0.01). In addition, subgroup analysis showed that single probiotic strains, receiving probiotic supplements over 12 weeks, and doses >1 × 109 CFU/g were more beneficial for improving cognitive impairment.

According to this meta-analysis, probiotic supplementation had a highly significant effect on cognitive function in people with cognitive impairment or Alzheimer's disease. For people without cognitive impairment, probiotic supplementation may be ineffective.

Gut microbiota is a complex ecosystem, strictly linked to health and disease, as a balanced composition (referred as eubiosis) is necessary for several physiological functions, while an unbalanced composition (dysbiosis) is often associated to pathological conditions and/or diseases. An altered microbiota could be positively affected and partially restored through probiotic supplementation, among others. This review addresses the effects of probiotics in several conditions, used as case-studies (colorectal cancer, neuro-psychiatric diseases, intestinal diseases, obesity, diabetes, metabolic syndrome, immune system, and musculoskeletal system disorders) by pointing out the clinical outcomes, the mode of action, mainly related to the production of short chain fatty acids (SCFA), the impact of probiotic dose and mode of supplementation, as well as trying to highlight a hit of the most used genera.

This study presents results of our randomized clinical trial studying the effect of human probiotics on memory and psychological and physical measures following our study protocol registered at clinicaltrials.gov NCT05051501 and described in detail in our previous paper.

Community dwelling participants aged between 55 and 80  years were randomly assigned to receive a single dose of 10⁶ colony-forming units of human Streptococcus thermophilus GH, Streptococcus salivarius GH NEXARS, Lactobacilus plantarum GH, and Pediococcus pentosaceus GH or placebo. A cross-over design allowed each group to receive probiotics and placebo for 3  months each in reverse order. A small subset of participants was examined online due to the COVID-19 pandemic. After 6  months a small number of volunteers were additionally assessed after 2  months without any intervention. Primary outcome measures included changes in cognitive functions assessed using brief tests and a neuropsychological battery and changes in mood assessed using validated questionnaires. Secondary outcome measures included changes in self-report and subjective measures using depression and anxiety questionnaires, seven visual analog scales of subjective feelings (memory, digestion, etc.), and physical performance.

At baseline, the probiotic-placebo group A (n = 40, age 69 ± 7 years, education 16 ± 3 years, 63% females, body mass index 28.5 ± 6, subjective memory complaint in 43%) did not differ from the placebo-probiotic group B (n = 32) in any of the sociodemographic characteristics and evaluated measures including cognitive status. At follow-up visits after 3, 6, and 8  months, no cross-sectional differences in any of the measures were found between the groups except worse sentence recall of the ALBA test after 3  months of probiotic use. Score changes were not observed for all cognitive tests but one in any group between visits 1 and 3 and between visits 3 and 6. The only change was observed for the TMT B test after the first three months but no change was observed after the second three months.

The treatment with human probiotics and prebiotics did not improve cognitive, affective, or physical measures in community-dwelling individuals with normal or mildly impaired cognitive functions.

clinicaltrials.gov, identifier NCT05051501.

Cognitive decline and constipation are common complications in the elderly. Probiotics are potential therapeutic agents to ameliorate cognitive impairment through gut-brain axis. Several clinical studies have investigated the beneficial effects of probiotics on cognitive impairment and constipation in elderly. However, a quantitative meta-analysis is required to evaluate the efficacy of probiotics on cognitive function and constipation. Thirteen clinical studies were included in this meta-analysis. We examined the risk of bias assessment and heterogeneity of eight studies for cognition and five studies for constipation, followed by group and subgroup meta-analyses using a random-effects model to evaluate the potential of probiotic supplements on cognition function and constipation in aged people. The results of the pooled meta-analysis revealed that probiotic supplementation did not improve the cognitive rating scale assessment for all studies (estimate = 0.13; 95%CI [-0.18, 0.43]; p = 0.41; I2 = 83.51%). However, subgroup analysis of single strain supplementation showed improved cognitive function in elderly people (estimate = 0.35; 95%CI [0.02, 0.69]; p = 0.039; I2 = 19.19%) compared to multiple strains. Probiotics also enhanced defecation frequency in constipated patients (estimate = 0.27; 95%CI [0.05, 0.5]; p = 0.019; I2 = 67.37%). Furthermore, probiotic supplementation resulted in higher fecal Lactobacillus counts than placebo (estimate = 0.37; 95%CI [0.05, 0.69]; p = 0.026; I2 = 21.3%). Subgroup analysis indicated that a probiotic intervention period of ≥4 weeks was more effective (estimate = 0.35; 95%CI [0.01, 0.68]; p = 0.044; I2 = 0%) in reducing constipation symptoms than a short intervention duration. Based on these results, probiotic supplementation could be a potential intervention to reduce constipation symptoms in the elderly population. The heterogeneity between studies is high, and limited trials are available to evaluate the cognitive function of aged individuals using probiotics. Therefore, further studies are required to determine the effect of probiotics on cognition.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive impairment and neuroinflammation. Recent research has revealed the crucial role of gut microbiota and microbial metabolites in modulating AD. However, the mechanisms by which the microbiome and microbial metabolites affect brain function remain poorly understood. Here, we review the literature on changes in the diversity and composition of the gut microbiome in patients with AD and in animal models of AD. We also discuss the latest progress in understanding the pathways by which the gut microbiota and microbial metabolites from the host or diet regulate AD. By understanding the effects of dietary components on brain function, microbiota composition, and microbial metabolites, we examine the potential for manipulation of the gut microbiota through dietary intervention to delay the progression of AD. Although it is challenging to translate our understanding of microbiome-based approaches to dietary guidelines or clinical therapies, these findings provide an attractive target for promoting brain function.