Alzheimer's disease is a common neurodegenerative disorder in older adults. Despite its prevalence, its pathogenesis remains unclear. In addition to the most widely accepted causes, which include excessive amyloid-beta aggregation, tau hyperphosphorylation, and deficiency of the neurotransmitter acetylcholine, numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition. Dopamine is a crucial catecholaminergic neurotransmitter in the human body. Dopamine-associated treatments, such as drugs that target dopamine receptor D and dopamine analogs, can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations. However, therapeutics targeting the dopaminergic system are associated with various adverse reactions, such as addiction and exacerbation of cognitive impairment. This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease, focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs. The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease, thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.

Diet can regulate systemic inflammation and the composition of the gut microbiota, which may play a significant role in the development of cognitive impairment. This study aims to explore the impact of inflammatory diets on gut microbes in patients with mild cognitive impairment (MCI) and to investigate the relationship between these microbes and cognitive function. Dietary inflammatory properties and gut microorganisms were analyzed using the energy-adjusted dietary inflammatory index (E-DII) and 16S rRNA in MCI patients. No significant differences in the diversity of the gut microbiota were observed among different E-DII groups. In the anti-inflammatory diet group, the gut microbiomes exhibited higher abundances of Christensenella and Oribacterium, while Streptococcus, Ruthenibacterium, Enterobacter, and Conservatibacter were significantly more prevalent in the pro-inflammatory diet group (P < 0.05). Specific oral and gut genera were found to be associated with MoCA, AVLT-LR, and STT-A scores (P < 0.05). A higher dietary inflammatory index was linked to lower overall cognitive function, as well as deficits in language, attention, and executive function. Additionally, specific gut microbial compositions were associated with cognitive performance.

This article synthesizes findings, from the Autism/Dementia Work Group of the 2nd International Summit on Intellectual Disabilities and Dementia, on the nature of autism/autism spectrum disorder and later-age neuropathologies, particularly dementia. The convened group of experts explored genetic, neurobiological, and environmental risk factors that may affect the lifespan and lived experiences of older adults with autism. A review of current literature indicates a lack of comprehensive information on the demographics and factors associated with aging in autistic adults. However, our understanding of autism is evolving, challenging traditional views of it as a static, inherited neurodevelopmental disorder. The relationship between autism and other neurodevelopmental conditions-such as Down syndrome, fragile X syndrome, and tuberous sclerosis complex-reflects the complex genetic landscape of neurodevelopmental disorders. These genetic and familial factors may contribute to progressive health challenges and cognitive decline in later life. Key findings reveal a complex link between autism and dementia, despite limited research on this relationship, particularly among older adults. The overall prevalence of dementia in this population appears to be influenced by co-occurring intellectual disabilities, particularly Down syndrome. While the association between autism and specific types of dementia is still not well understood, the reviewed evidence suggests a notable connection with frontotemporal dementia, although causality has not been established. Exploration of biomarkers may offer further insights. Currently, the relationship between autism, cognitive health, and cognitive decline in older adults remains a complex and underexplored area of research.

The intestinal microbiome is essential for gastrointestinal and overall health, yet its response to air pollution in children remains underexplored. In a study involving 412 young children from the ENVIRONAGE cohort, stool samples were analysed via Illumina Miseq sequencing to assess microbiome alpha diversity (observed richness, species evenness, and Shannon diversity) and composition. Exposure to previous year particulate air pollution (black carbon, PM2.5, coarse PM, and PM10) was modeled using high-resolution spatial-temporal interpolation models. Multiple linear regression models were adjusted for a priori selected covariables and stratified by sex. Furthermore, we performed a differential relative abundance analysis at family and genus level, while accounting for the same covariables. Statistically significant effect modification by sex was apparent for several intestinal alpha diversity indices and air pollutants. In boys, we observed negative associations between particulate air pollution exposure and intestinal microbiome richness (estimates ranging from -5.55 to -9.06 per interquartile range (IQR) increase in particulate air pollution exposure) and Shannon diversity (estimates ranging from -0.058 to -0.095 per IQR increase). Differently, in girls non-significant positive associations were observed with species evenness (estimates ranging from 0.019 to 0.020 per IQR increase) and Shannon diversity (estimate 0.065 per IQR increase in black carbon). After multiple testing correction, we reported several bacterial families and genera (Streptococcaceae, Clostridiales Incertae Sedis XIII, Coriobacteriaceae, Streptococcus, and Paraprevotella) to be oppositely associated with particulate air pollution exposure in boys and girls. Our findings show a sex-dependent association between particulate air pollution exposure and intestinal microbiome composition, highlighting boys as potentially more vulnerable to diversity loss associated with childhood exposure to particulate pollution.

Alzheimer's disease (AD), a prevalent neurodegenerative disorder, represents a significant global health challenge, characterized by cognitive decline and neuroinflammation. Recent investigations have highlighted the critical role of the gut-brain axis in the pathogenesis of AD, particularly focusing on the influence of short-chain fatty acids (SCFAs), metabolites produced by the gut microbiota through the fermentation of dietary fiber. Among SCFAs, butyrate has emerged as a crucial mediator, positively impacting various pathological processes associated with AD, including epigenetic regulation, neuroinflammation modulation, maintenance of the blood-brain barrier (BBB), enhanced intestinal integrity, regulation of brain metabolism, and interference with amyloid protein formation as well as tau protein hyperphosphorylation. Furthermore, distinctions in butyrate profile and microbial communities have been observed between AD patients and healthy individuals, underscoring the importance of gut microbiota in AD progression. This review summarizes the current understanding of the many functions of butyrate in reducing the consequences of AD and emphasizes the possibility of addressing the gut microbiota as a therapeutic approach to managing AD.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Most current treatments for TBI and other neurological disorders focus on the brain, often overlooking the significant contributions of peripheral organs to disease progression. Emerging evidence suggests that organs such as the liver and adipose tissue play crucial roles in TBI pathogenesis. The liver synthesizes lipids and proteins vital for brain function, while adipose tissue provides hormones and metabolites that influence brain activity. New research indicates that the liver and adipose tissue work in concert with the hypothalamus to regulate essential processes, such as body temperature, which become disrupted in TBI. Additionally, the brain-peripheral axis-a complex network of visceral nerve pathways, hormones, and metabolites-plays a bidirectional role in regulating brain plasticity and function. Understanding how TBI leads to dysregulation of the liver, adipose tissue, and other organs could unlock new therapeutic opportunities for treating TBI and related neurological disorders. The intricate autonomic network involving hypothalamic and enteric neurons, along with visceral nerve pathways and hormones, presents both pathological targets and therapeutic potential. We examine scientific evidence suggesting that correcting disturbances in systemic physiology could enhance the brain's capacity for healing. However, the interdependence of this autonomic network implies that treating dysfunction in one area may affect others. Therefore, we also explore the mechanisms by which diet and exercise can comprehensively impact the brain-peripheral axis, supporting the healing process. CHEMICAL COMPOUNDS: D-Fructose (PubChem CID 2723872); docosahexaenoic acid (PubChem CID 45934466); eicosapentaenoic acid (PubChem 5282847).

The extraction of polysaccharides from wood by-products is recognized as a green re-utilization approach to shape a recycling-oriented society. In this research, we identified the structural properties of arabinogalactan (AG) extracted from Larix sibirica Ledeb wood chips and verified its efficacy as an additive in broiler framing. Results showed that the molecular weight of AG is 19.805 KDa. Methylation analysis and NMR spectra indicate that AG has a 1,6-linked Galp backbone, side residues mainly branched at C-1,3,6 on β-D-Galp. The Ara residues were substituted at C-3 of 1,6-linked Galp consisting of α-L-Araf-(1→3)-α-L-Araf-(1 → 3)-α-L-Araf (1→ and α-L-Araf-(1 → 4) β-D-Galp-(1 → 3)-β-D-Galp-(1→. As a dietary supplement in broiler model, AG treatment improved the body weight of broilers especially breast and leg muscle weight. Furthermore, AG could regulate host immune response, gut microbiota composition, and metabolic activity, especially promoting lipid metabolism. By means of serum non-targeted metabolomics analysis, enrichment of pantothenate and CoA biosynthesis and beta-alanine metabolism pathways could be determined. AG treatment led to a rise in bacteria that produce SCFAs, with elevated concentrations of acetic and butyric acids. In conclusion, AG can be considered as a potential dietary supplement to beneficially affect host's health status.

The rumen microbiota plays a vital role in the nutrient metabolism affecting the growth of velvet antler. However, the fermentation patterns and dynamics of the rumen microbiota across growth stages of velvet antler remain largely unexplored. Here, we employed an in vitro fermentation approach to assess fermentation parameters and microbial composition in the rumen liquid of sika deer during the early growth (EG), metaphase growth (MG), and fast growth (FG) phases . Our findings indicated that the levels of short-chain fatty acids (SCFAs), ammonia nitrogen, and gas production increased over fermentation time in all three groups. The concentrations of total SCFAs, ammonia nitrogen, and gas production, along with the proportions of butyrate, isobutyrate, and isovalerate, were markedly higher in the MG and FG groups compared with the EG group. Principal coordinate analysis highlighted significant variations in microbial communities among the EG, MG, and FG groups during the fermentation process. The abundances of Stomatobaculum and Blautia across the three groups increased over fermentation time, whereas Bacteroides, Lawsonibacter, Sporobacter, Papillibacter, Butyricicoccus, and Succiniclasticum exhibited higher abundances in MG or FG groups than in the EG group after 24 hours of fermentation. Co-occurrence network analysis uncovered positive correlations between butyrate levels and butyrate-producing bacteria (Stomatobaculum, Butyrivibrio) in the MG and FG groups. Additionally, there were positive correlations between proteolytic bacteria (Clostridium and Roseburia) and branched-chain volatile fatty acids in the FG group. These findings shed light on the fermentation patterns and microbial dynamics within the rumen of sika deer during different growth periods of velvet antler.IMPORTANCEVelvet antlers are distinctive and rapidly growing organs that hold significant value in traditional medicine. Through in vitro analysis, our study characterized the dynamics of microbiota and metabolites within the rumen liquid fermentation of sika deer throughout the different antler growth phase. We identified distinct microbial communities at various fermentation time points and observed shifts in fermentation patterns that paralleled antler development. These findings suggest a potentially pivotal role for these microbial dynamics in facilitating the growth process of velvet antlers.

Alzheimer's Disease (AD) is a debilitating neurocognitive disorder with an unclear underlying mechanism. Recent studies have implicated gut microbiota dysbiosis with the onset and progression of AD. The connection between gut microbiota and AD can significantly affect the prevention and treatment of AD patients. This systematic review summarizes primary outcomes of human and mouse AD models concerning gut microbiota alterations. A systematic literature search in February through March 2023 was conducted on PubMed, Embase, and Web of Science. We identified 711 as potential manuscripts of which 672 were excluded because of irrelevance to the identified search criteria. Primary outcomes include microbiota compositions of control and AD models in humans and mice. In total, 39 studies were included (19 mouse and 20 human studies), published between 2017 and 2023. We included studies involving well-established mice models of AD (5xFAD, 3xTg-AD, APP/PS1, Tg2576, and APPPS2) which harbor mutations and genes that drive the formation of Aß plaques. All human studies were included on those with AD or mild cognitive impairment. Among alterations in gut microbiota, most studies found a decreased abundance of the phyla Firmicutes and Bifidobacteria, a genus of the phylum Actinomycetota. An increased abundance of the phyla Bacteroidetes and Proteobacteria were identified in animal and human studies. Studies indicated that gut microbiota alter the pathogenesis of AD through its impact on neuroinflammation and permeability of the gastrointestinal tract. The ensuing increase in blood-brain barrier permeability may accelerate Aβ penetrance and formation of neuritic plaques that align with the amyloid hypothesis of AD pathogenesis. Further studies should assess the relationship between gut microbiota and AD progression and therapy preserving beneficial gut microbiota.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by Spa-EV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Some studies have confirmed that pathogens can cause infection through bacterial cultures on the surface of infectious keloids. However, further exploration of the comparison between infectious and non-infectious keloids and the bacterial flora of infectious foci is lacking. To investigate the differential flora of purulent secretions on the surface of infectious keloids compared to non-infectious keloids and to determine the microbial composition within the infectious foci. This case-control study involved 17 patients and obtained swab specimens from the surface of keloids in two groups, and from the infectious foci in the infectious group. Bacterial composition was analyzed using 16S ribosomal RNA sequencing. There were no statistical differences in the general condition of patients between the two groups. The presence of the phylum Actinobacteriota, and the orders Propionibacteriales and Corynebacteriales, as well as the genus Taibaiella, was greater on the surface of keloids in the infectious group. The most prevalent genera in infective sites were Staphylococcus, Peptoniphilus, and Cutibacterium. Microbial-associated gene pathways indicated a correlation with inflammation and tumor-like growth in keloids. There is a connection between infectious keloids and microorganisms, providing insights for predicting and treating keloid infections.

Alzheimer's disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer's learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and synaptic dysfunction. Emerging evidence suggests a significant relationship between gut microbiota and brain health, mediated through the gut-brain axis. Alterations in gut microbiota composition may influence AD progression by affecting molecular pathways and miRNA interactions.

We retrieved and analyzed microarray data from 34 tissue samples of AD patients and controls (GEO accession number GSE110298). Differentially expressed genes (DEGs) with the GCS score package in R, considering a p-value < 0.05 and logFC<-1 and logFC>1 to isolate significant gene clusters. Enrichment analysis of signaling pathways and gene ontology was conducted using Enrichr, KEGG, Panther, DAVID, and shiny GO databases. Protein-protein interactions were visualized with Networkanalyst and CytoScape. Gut microbiota in 200 CE patients was analyzed using next-generation sequencing (NGS) data from gutMDisorder and GMrepo databases. miRNA interactions were evaluated using miEAA, Targetscan, MienTurnet, and miRnet databases.

Significant reductions in microbial taxa, including Clostridia (LDA score -4.878208), Firmicutes (LDA score -4.817032), and Faecalibacterium (LDA score -4.40714), were observed in AD patients. Pathway analysis highlighted the involvement of Axon guidance, ErbB, and MAPK signaling pathways in AD. Venn diagram analysis identified 619 intersecting genes in brain and gut tissues, emphasizing pathways such as Axon Guidance and Cell Cycle. miRNA analysis revealed important regulatory miRNAs, including hsa-let-7c, hsa-mir-125b-2, and hsa-mir-145, which target key transcription factors involved in AD pathology.

The study demonstrates significant dysbiosis in the gut microbiota of AD patients and underscores the potential role of gut microbiota in AD progression through altered signaling pathways and miRNA interactions. These findings highlight the need for further research into microbiota-based interventions as potential therapeutic strategies for AD.

Numerous studies conducted over the last ten years have shown a strong correlation between the gut microbiota and the onset and progression of Alzheimer's disease (AD). However, the exact underlying mechanism is still unknown. An ongoing communication mechanism linking the gut and the brain is highlighted by the term "microbiota-gut-brain axis," which was originally coined the "gut-brain axis." Key metabolic, endocrine, neurological, and immunological mechanisms are involved in the microbiota‒gut‒brain axis and are essential for preserving brain homeostasis. Thus, the main emphasis of this review is how the gut microbiota contributes to the development of AD and how various natural products intervene in this disease. The first part of the review provides an outline of various pathways and relationships between the brain and gut microbiota, and the second part provides various mechanisms involved in the gut microbiota and AD. Finally, this review provides knowledge about natural products and their effectiveness in treating gut microbiota-induced AD. AD may be treated in the future by altering the gut microbiota with a customized diet, probiotics/prebiotics, plant products, and natural products. This entails altering the microbiological partners and products (such as amyloid protein) that these partners generate.

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.

The interplay between gut microbiota and host health is crucial for maintaining the overall health of the body and brain, and it is even more crucial how changes in the bacterial profile can influence the aftermath of traumatic brain injury (TBI). We studied the effects of probiotic treatment after TBI to identify potential changes in hepatic lipid species relevant to brain function. Bioinformatic analysis of the gut microbiota indicated a significant increase in the Firmicutes/Bacteroidetes ratio in the probiotic-treated TBI group compared to sham and untreated TBI groups. Although strong correlations between gut bacteria and hepatic lipids were found in sham mice, TBI disrupted these links, and probiotic treatment did not fully restore them. Probiotic treatment influenced systemic glucose metabolism, suggesting altered metabolic regulation. Behavioral tests confirmed memory improvement in probiotic-treated TBI mice. While TBI reduced hippocampal mRNA expression of CaMKII and CREB, probiotics reversed these effects yet did not alter BDNF mRNA levels. Elevated pro-inflammatory markers TNF-α and IL1-β in TBI mice were not significantly affected by probiotic treatment, pointing to different mechanisms underlying the probiotic benefits. In summary, our study suggests that TBI induces dysbiosis, alters hepatic lipid profiles, and preemptive administration of Lactobacillus helveticus and Bifidobacterium longum probiotics can counter neuroplasticity deficits and memory impairment. Altogether, these findings highlight the potential of probiotics for attenuating TBI's detrimental cognitive and metabolic effects through gut microbiome modulation and hepatic lipidomic alteration, laying the groundwork for probiotics as a potential TBI therapy.

Background/Objectives: The role of the gut microbiome in the development and progression of many diseases has received increased attention in recent years. Boron, a trace mineral found in dietary sources, has attracted interest due to its unique electron depletion and coordination characteristics in chemistry, as well as its potential role in modulating the gut microbiota. This study investigates the effects of inorganic boron derivatives on the gut microbiota of mice. Methods: For three weeks, boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium perborate tetrahydrate (SPT) were dissolved (200 mg/kg each) in drinking water and administered to wild-type BALB/c mice. The composition of the gut microbiota was analyzed to determine the impact of these treatments. Results: The administration of BA significantly altered the composition of the gut microbiota, resulting in a rise in advantageous species such as Barnesiella and Alistipes. Additionally, there was a decrease in some taxa associated with inflammation and illness, such as Clostridium XIVb and Bilophila. Notable increases in genera like Treponema and Catellicoccus were observed, suggesting the potential of boron compounds to enrich microbial communities with unique metabolic functions. Conclusions: These findings indicate that boron compounds may have the potential to influence gut microbiota composition positively, offering potential prebiotic effects. Further research with additional analyses is necessary to fully understand the interaction between boron and microbiota and to explore the possibility of their use as prebiotic agents in clinical settings.

A systematic review and meta-analysis examined the impact of gut microbiota in Alzheimer's disease (AD) pathogenesis. Dysbiosis may influence neurodegeneration by affecting gut permeability and neurotrophic factors, leading to cognitive decline. The study analyzed microbiome differences between patients with AD and healthy individuals, as well as the impact of various interventions in both preclinical and clinical studies. Of 60 studies reviewed, 12 were excluded from the meta-analysis due to unsuitable data or lack of control groups. Meta-analyses revealed significant cognitive impairment in AD patients and animal models, with specific tests identifying these deficits. Notably, Bacteroides levels were higher in patients with AD, whereas probiotics improved Prevotella levels. Natural treatments increased Bacteroidetes and reduced Firmicutes in animal models. The findings emphasize the need for standardized methods to develop therapies targeting the gut microbiota to restore cognition in AD. Understanding individual dysbiosis could further clarify the cognitive effects of the gut-brain axis.

Dysbiosis in the gut microbiota is linked to cognitive decline in Alzheimer's disease (AD).Patients with AD show significant differences in Bacteroides levels compared to healthy individuals.Probiotic treatments increase Prevotella levels in AD animal models.Natural agents boost Bacteroidetes and reduce Firmicutes in AD animal models.Human studies show no consistent effects of gut microbiota interventions on cognitive function in AD.

An escalating body of clinical trials and observational studies hints at a plausible link between gut flora and postpartum depression (PPD). The definitive causal dynamics between these two entities remain shrouded in ambiguity. Therefore, in this study, we employed the two-sample Mendelian randomization approach to ascertain the causal link between gut microbiota and PPD.

Summary-level GWAS data related to the human gut microbiota were obtained from the international consortium MiBioGen and the Dutch Microbiome Project (species). For PPD, GWAS data were derived from the FinnGen biobank, consisting 57,604 cases and 596,601 controls. The inverse variance weighted method (IVW) as the cornerstone of our analytical approach. Subsequent to this, a comprehensive suite of tests for pleiotropy and heterogeneity were conducted to ensure the reliability and robustness of our findings.

We identified 12 bacterial taxa associated with the risk of PPD. Veillonellaceae, Ruminococcaceae UCG 011, Bifidobacterium adolescentis, Paraprevotella clara, Clostridium leptum, Eubacterium siraeum, Coprococcus catus exhibited an inversely associated with the risk of PPD. Alphaproteobacteria, Roseburia, FamilyXIIIAD3011group, Alistipes onderdonkii, Bilophila wadsworthia showed a positive correlation with the risk of PPD.

The GWAS data derived from the MiBioGen consortium, DMP, and FinnGen consortium, may introduce selection bias. Moreover, the data primarily originates from European populations, hence extrapolating these results to diverse populations should be approached with caution. The etiological factors behind PPD remain enigmatic, alluding to the existence of potential undisclosed confounders.

Based on this MR analysis, we found a causal relationship between certain gut microbial communities and PPD. Future clinical studies can further explore the treatment of PPD through the combined use of microorganisms. This not only offers insights into the pathogenesis of PPD but also lays the foundation for utilizing gut microbiota as biotherapeutics in treating neurological disorders.

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.

There are complex interactions between the gut and the brain. With increasing research on the relationship between gut microbiota and brain function, accumulated clinical and preclinical evidence suggests that gut microbiota is intimately involved in the pathogenesis of neurodegenerative diseases (NDs). Increasingly studies are beginning to focus on the association between gut microbiota and central nervous system (CNS) degenerative pathologies to find potential therapies for these refractory diseases. In this review, we summarize the changes in the gut microbiota in Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis and contribute to our understanding of the function of the gut microbiota in NDs and its possible involvement in the pathogenesis. We subsequently discuss therapeutic approaches targeting gut microbial abnormalities in these diseases, including antibiotics, diet, probiotics, and fecal microbiota transplantation (FMT). Furthermore, we summarize some completed and ongoing clinical trials of interventions with gut microbes for NDs, which may provide new ideas for studying NDs.

Evidence shows that neurodegenerative and neuropsychiatric disorders are influenced by alterations in the gut microbiome. Various diseases have been linked to microbiome dysbiosis, yet there are inconclusive data regarding which microorganisms are associated with each disorder. The aim of our study is to systematically review the recent literature of the past decade to clarify whether the gut microbiome contributes to the understanding of pathogenesis and progression of neurodegenerative disorders. Most included studies showed a strong correlation between the relative abundance of certain microorganisms, mainly species of the phyla Firmicutes and Bacteroidetes, and disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). It is speculated that the microorganisms and their byproducts have a significant role in brain protein accumulation, neuro-inflammation, and gut permeability. The estimation of microbial populations could potentially improve clinical outcomes and hinder the progression of the disease. However, further research is needed to include more diseases and larger patient samples and identify specific species and subspecies associated with these disorders.

The gut microbiota (GM) is hypothesized to play roles in Alzheimer's disease (AD) pathogenesis. In recent years, many GM composition and abundance investigations in AD patients have been conducted; however, despite this work, some results remain controversial. Therefore, we conducted a systematic review and meta-analysis using 16S ribosomal RNA (16S rRNA) sequencing to explore GM alterations between patients with AD spectrum and healthy controls (HCs).

A systematic and comprehensive literature search of PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc database, WanFang database and Social Sciences Citation Index databases was conducted from inception to January 2023. Inclusion and exclusion criteria were strictly defined, and two researchers independently screened and extracted information from selected studies. Data quality were evaluated according to the "Cochrane system evaluator manual" and pooled data were comprehensively analyzed using Stata 14 software with standardized mean differences (SMDs) and 95% confidence intervals (95% CIs) used to measure effect sizes. Also, geographical heterogeneity effects (related to cohorts) on GM abundance were examined based on subgroup meta-analyses if sufficient studies reported outcomes. Finally, publication bias was assessed using funnel plots.

Out of 1566 articles, 13 studies involving 581 patients with AD spectrum and 445 HCs were deemed eligible and included in our analysis. In summary, a decreased microbiota alpha diversity and a significantly distinct pattern of clustering with regard to beta diversity were observed in AD spectrum patients when compared with HCs. Comparative analyses revealed a decreased Ruminococcus, Faecalibacterium, Lachnospira, Dialister, Lachnoclostridium, and Roseburia abundance in AD spectrum patients while Phascolarctobacterium, Lactobacillus, and Akkermansia muciniphila were more enriched in patients when compared to HCs. Furthermore, regional variations may have been in play for intestinal microbes such as Bacteroides, Bifidobacterium, and Alistipes.

Our meta-analysis identified alterations in GM abundance in patients with AD spectrum, with 12 genera from four major phyla significantly associated with AD. Moreover, we provided evidence for region-specific alterations in Bacteroides, Bifidobacterium, and Alistipes abundance. These findings may have profound implications for the development of innovative GM-based strategies to prevent and treat AD.

https://doi.org/10.37766/inplasy2024.6.0067, identifier INPLASY202460067.

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.

Pseudoxanthoma elasticum (PXE) is a rare autosomal disorder with a variable phenotype that may be modulated by environmental factors. Plasma vitamin K (VK) levels may be involved in the ectopic calcification process observed in PXE. Since VK2 is predominantly produced by the gut microbiota, we hypothesized that changes in the gut microbiota of PXE patients might exacerbate the calcification process and disease symptoms.

Twenty PXE patients were included in the study and 60 gut microbiota profiles from the Biofortis laboratory database were used as controls.

The Rhodospirillaceae family was more abundant in the PXE group while the Sphingomonadaceae family was more abundant in the control group. In a PXE severity subgroup analysis, microbiota dispersion was lower in "severe" than in "non-severe" patients, which was confirmed by permutation multivariate analysis of variance at the phylum, family and genus ranks. However, no significant association was found in a model incorporating relative abundance of bacterial families, severity score, and different blood and fecal VK species.

These results suggest slight compositional changes in the gut microbiota of PXE patients. Further studies are needed to substantiate their impact on VK metabolism and the calcification process.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system and a leading cause of neurological disability in young adults. Clinical presentation and disease course are highly heterogeneous. Typically, disease progression occurs over time and is characterized by the gradual accumulation of disability. The risk of developing MS is driven by complex interactions between genetic and environmental factors, including the gut microbiome. How the commensal gut microbiota impacts disease severity and progression over time remains unknown. In a longitudinal study, disability status and associated clinical features in 58 MS patients were tracked over 4.2 ± 0.98 years, and the baseline fecal gut microbiome was characterized via 16S amplicon sequencing. Progressor status, defined as patients with an increase in Expanded Disability Status Scale (EDSS), were correlated with features of the gut microbiome to determine candidate microbiota associated with risk of MS disease progression. We found no overt differences in microbial community diversity and overall structure between MS patients exhibiting disease progression and non-progressors. However, a total of 41 bacterial species were associated with worsening disease, including a marked depletion in Akkermansia, Lachnospiraceae, and Oscillospiraceae, with an expansion of Alloprevotella, Prevotella-9, and Rhodospirillales. Analysis of the metabolic potential of the inferred metagenome from taxa associated with progression revealed enrichment in oxidative stress-inducing aerobic respiration at the expense of microbial vitamin K2 production (linked to Akkermansia), and a depletion in SCFA metabolism (linked to Oscillospiraceae). Further, as a proof of principle, statistical modeling demonstrated that microbiota composition and clinical features were sufficient to predict disease progression. Additionally, we found that constipation, a frequent gastrointestinal comorbidity among MS patients, exhibited a divergent microbial signature compared with progressor status. These results demonstrate a proof of principle for the utility of the gut microbiome for predicting disease progression in MS in a small well-defined cohort. Further, analysis of the inferred metagenome suggested that oxidative stress, vitamin K2, and SCFAs are associated with progression, warranting future functional validation and mechanistic study.

FRILEUX, M., BOLTRI M. and al. Cognition and Gut microbiota in schizophrenia spectrum and mood disorders: a Systematic Review. NEUROSCI BIOBEHAV REV (1) 2024 Schizophrenia spectrum disorders and major mood disorders are associated with cognitive impairments. Recent studies suggest a link between gut microbiota composition and cognitive functioning. Here, we review the relationship between gut microbiota and cognition in these disorders. To do this, we conducted a systematic review, searching Cochrane Central Register of Controlled Trials, EBSCOhost, Embase, Pubmed, Scopus, and Web of Science. Studies were included if they investigated the relationship between gut microbiota composition and cognitive function through neuropsychological assessments in patients with bipolar, depressive, schizophrenia spectrum, and other psychotic disorders. Ten studies were identified. Findings underscore a link between gut dysbiosis and cognitive impairment. This relationship identified specific taxa (Haemophilus, Bacteroides, and Alistipes) as potential contributors to bolstered cognitive performance. Conversely, Candida albicans, Toxoplasma gondii, Streptococcus and Deinococcus were associated with diminished performance on cognitive assessments. Prebiotics and probiotics interventions were associated with cognitive enhancements, particularly executive functions. These results emphasize the role of gut microbiota in cognition, prompting further exploration of the underlying mechanisms paving the way toward precision psychiatry.

Previous studies have suggested a potential association between gut microbiota and neurological and psychiatric disorders. However, the causal relationship between gut microbiota and cognitive performance remains uncertain.

A two-sample Mendelian randomization (MR) study used SNPs linked to gut microbiota (n = 18,340) and cognitive performance (n = 257,841) from recent GWAS data. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were employed. Heterogeneity was assessed via Cochran's Q test for IVW. Results were shown with funnel plots. Outliers were detected through leave-one-out method. MR-PRESSO and MR-Egger intercept tests were conducted to address horizontal pleiotropy influence.

Limited to European populations, generic level, and potential confounding factors.

IVW analysis revealed detrimental effects on cognitive perfmance associated with the presence of genus Blautia (P = 0.013, 0.966[0.940-0.993]), Catenibacterium (P = 0.035, 0.977[0.956-0.998]), Oxalobacter (P = 0.043, 0.979[0.960-0.999]). Roseburia (P < 0.001, 0.935[0.906-0.965]), in particular, remained strongly negatively associated with cognitive performance after Bonferroni correction. Conversely, families including Bacteroidaceae (P = 0.043, 1.040[1.001-1.081]), Rikenellaceae (P = 0.047, 1.026[1.000-1.053]), along with genera including Paraprevotella (P = 0.044, 1.020[1.001-1.039]), Ruminococcus torques group (P = 0.016, 1.062[1.011-1.115]), Bacteroides (P = 0.043, 1.040[1.001-1.081]), Dialister (P = 0.027, 1.039[1.004-1.074]), Paraprevotella (P = 0.044, 1.020[1.001-1.039]) and Ruminococcaceae UCG003 (P = 0.007, 1.040[1.011-1.070]) had a protective effect on cognitive performance.

Our results suggest that interventions targeting specific gut microbiota may offer a promising avenue for improving cognitive function in diseased populations. The practical application of these findings has the potential to enhance cognitive performance, thereby improving overall quality of life.

Cefotaxime (CTX) is an easily detectable antibiotic pollutant in the water environment, but little is known about its toxic effects on aquatic invertebrates, especially on the intestine. Here, we determined the oxidative stress conditions of A. sinica under CTX exposure with five concentrations (0, 0.001, 0.01, 0.1 and 1 mg/L) for 14 days. After that, we focused on changes in intestinal tissue morphology and gut microbiota in A. sinica caused by CTX exposure at 0.01 mg/L. We found malondialdehyde (MDA) was elevated in CTX treatment groups, suggesting the obvious antibiotic-induced oxidative stress. We also found CTX exposure at 0.01 mg/L decreased the villus height and muscularis thickness in gut tissue. The 16S rRNA gene analysis indicated that CTX exposure reshaped the gut microbiota diversity and community composition. Proteobacteria, Actinobacteriota and Bacteroidota were the most widely represented phyla in A. sinica gut. The exposure to CTX led to the absence of Verrucomicrobia in dominant phyla and an increase in Bacteroidota abundance. At the genus level, eleven genera with an abundance greater than 0.1% exhibited statistically significant differences among groups. Furthermore, changes in gut microbiota composition were accompanied by modifications in gut microbiota functions, with an up-regulation in amino acid and drug metabolism functions and a down-regulation in xenobiotic biodegradation and lipid metabolism-related functions under CTX exposure. Overall, our study enhances our understanding of the intestinal damage and microbiota disorder caused by the cefotaxime pollutant in aquatic invertebrates, which would provide guidance for healthy aquaculture.

Extensive evidence demonstrates correlations among gut microbiota, lipid metabolism and cognitive function. However, there is still a lack of researches in the field of late-life depression (LLD). This research targeted at investigating the relationship among gut microbiota, lipid metabolism indexes, such as total free fatty acids (FFAs), and cognitive functions in LLD.

Twenty-nine LLD patients from the Cognitive Outcome Cohort Study of Depression in Elderly were included. Cognitive functions were estimated through the Chinese version of Montreal Cognitive Assessment (MoCA). Blood samples were collected to evaluate serum lipid metabolism parameters. Fecal samples were evaluated for gut microbiota determination via 16S rRNA sequencing. Spearman correlation, linear regression and mediation analysis were utilized to explore relationship among gut microbiota, lipid metabolism and cognitive function in LLD patients.

Spearman correlation analysis revealed significant correlations among Akkermansia abundance, total Free Fatty Acids (FFAs) and MoCA scores (P < 0.05). Multiple regression indicated Akkermansia and total FFAs significantly predicted MoCA scores (P < 0.05). Mediation analysis demonstrated that the correlation between decreased Akkermansia relative abundance and cognitive decline in LLD patients was partially mediated by total FFAs (Bootstrap 95%CI: 0.023-0.557), accounting for 43.0% of the relative effect.

These findings suggested a significant relationship between cognitive functions in LLD and Akkermansia, as well as total FFAs. Total FFAs partially mediated the relationship between Akkermansia and cognitive functions. These results contributed to understanding the gut microbial-host lipid metabolism axis in the cognitive function of LLD.

Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis (ALS) have previously been reported. This study aimed to examine the microbiota in the nasal cavity of ALS.

Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled. High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) gene V3-V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa, predict function, and conduct correlation analysis between specific taxa and clinical features.

The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members. Genera Gaiella , Sphingomonas , Polaribacter _1, Lachnospiraceae _NK4A136_group, Klebsiella , and Alistipes were differentially enriched in ALS patients compared to controls. Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects (unweighted UniFrac P = 0.001), while Linear discriminant analysis Effect Size (LEfSe) analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level, whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients. Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised (ALSFRS-R; rs = 0.349, P = 0.020 and rs = 0.393, P = 0.008), while Prevotella -9 and Bacteroides operational taxonomic units (OTUs) were positively associated with lung function (FVC) in ALS patients ( rs = 0.304, P = 0.045, and rs = 0.300, P = 0.048, respectively). Prevotella -1 was positively correlated with white blood cell counts (WBC, rs = 0.347, P = 0.021), neutrophil percentage (Neu%, rs = 0.428, P = 0.004), and neutrophil-to-lymphocyte ratio (NLR, rs = 0.411, P = 0.006), but negatively correlated with lymphocyte percentage (Lym%, rs = -0.408, P = 0.006). In contrast, Streptococcus was negatively associated with Neu% ( rs = -0.445, P = 0.003) and NLR ( rs = -0.436, P = 0.003), while positively associated with Lym% ( rs = 0.437, P = 0.003). No significant differences in nasal microbiota richness and evenness were detected among the severe and mild ALS patients.

ALS is accompanied by altered nasal microbial community composition and diversity. The findings presented here highlight the need to understand how dysbiosis of nasal microbiota may contribute to the development of ALS.

Cognitive impairment is a clinical manifestation that occurs in the course of dementia like Alzheimer's disease. The association between cognitive impairment and gut microbiota is unclear.

We aimed to identify gut microbiota characteristics and key gut microbiota biomarkers associated with cognitive impairment in a relatively large cohort of older adults in China.

A total of 229 adults aged ≥60 years from Shenzhen, China were recruited into this cross-sectional study. Participants were divided into cognitive impairment (CI) and no cognitive impairment (NCI) groups according to the results of the Mini-Mental State Examination. Diversity analysis and network analysis were used to characterize the gut microbiota between the two groups. The linear discriminant analysis effect size method and machine learning approaches were sequentially performed to identify gut microbiota biomarkers. The relationship between biomarkers and lifestyle factors was explored using Transformation-based redundancy analysis (tb-RDA).

A total of 74 CI participants and 131 NCI participants were included in the analysis. The CI group demonstrated lower α-diversity compared to the NCI group (Shannon: 2.798 versus 3.152, p < 0.001). The density of the gut microbiota interaction network was lower in the CI group (0.074) compared to the NCI group (0.081). Megamonas, Blautia, Pseudomonas, Stenotrophomonas, and Veillonella were key biomarkers for CI. The tb-RDA revealed that increased fruit intake and exercise contribute to a higher abundance of Megamonas, Blautia, and Veillonella.

We identified a significantly reduced abundance of certain beneficial gut microbiota in older Chinese adults with cognitive impairment.

Ageing is a biological phenomenon that determines the impairment of cognitive performances, in particular, affecting memory. Inflammation and cellular senescence are known to be involved in the pathogenesis of cognitive decline. The gut microbiota-brain axis could exert a critical role in influencing brain homeostasis during ageing, modulating neuroinflammation, and possibly leading to inflammaging. Due to their anti-ageing properties, medicinal mushrooms can be utilised as a resource for developing pharmaceuticals and functional foods. Specifically, Hericium erinaceus (He), thanks to its bioactive metabolites, exerts numerous healthy beneficial effects, such as reinforcing the immune system, counteracting ageing, and improving cognitive performance. Our previous works demonstrated the capabilities of two months of He1 standardised extract oral supplementation in preventing cognitive decline in elderly frail mice. Herein, we showed that this treatment did not change the overall gut microbiome composition but significantly modified the relative abundance of genera specifically involved in cognition and inflammation. Parallelly, a significant decrease in crucial markers of inflammation and cellular senescence, i.e., CD45, GFAP, IL6, p62, and γH2AX, was demonstrated in the dentate gyrus and Cornus Ammonis hippocampal areas through immunohistochemical experiments. In summary, we suggested beneficial and anti-inflammatory properties of He1 in mouse hippocampus through the gut microbiome-brain axis modulation.

The goal of this study was to comprehensively investigate the characteristics of gut microbiota dysbiosis and metabolites levels in very low or extremely low birth weight (VLBW/ELBW) infants with white matter injury (WMI).

In this prospective cohort study, preterm infants with gestational age < 32 weeks and weight < 1.5 kg were investigated. Additionally, fecal samples were collected on days zero, 14d and 28d after admission to the intensive care unit. All subjects underwent brain scan via MRI and DTI at a corrected gestational age of 37 ~ 40 weeks. Based on the results of MRI examination, the VLBW/ELBW infants were divided into two groups: WMI and non-WMI. Finally, based on a multi-omics approach, we performed 16S rRNA gene sequencing, LC-MS/MS, and diffusion tension imaging to identify quantifiable and informative biomarkers for WMI.

We enrolled 23 patients with and 48 patients without WMI. The results of 16S RNA sequencing revealed an increase in the number of Staphylococcus and Acinetobacter species in the fecal samples of infants with WMI, as well as increasing levels of S. caprae and A._johnsonii. LEfSe analysis (LDA ≥ 4) showed that the WMI group carried an abundance of Staphylococcus species including S. caprae, members of the phyla Bacteroidota and Actinobacteriota, and Acinetobacter species. A total of 139 metabolic markers were significantly and differentially expressed between WMI and nWMI. KEGG pathway enrichment analysis revealed that the WMI group showed significant downregulation of 17 metabolic pathways including biosynthesis of arginine and primary bile acids. The WMI group showed delayed brain myelination, especially in the paraventricular white matter and splenium of corpus callosum. Staphylococcus species may affect WMI by downregulating metabolites such as cholic acid, allocholic acid, and 1,3-butadiene. Gut microbiota such as Acinetobacter and Bacteroidetes may alter white matter structurally by upregulating metabolites such as cinobufagin.

Based on 16S RNA sequencing results, severe gut microbiota dysbiosis was observed in the WMI group. The results might reveal damage to potential signaling pathways of microbiota-gut-brain axis in gut microbiota. The mechanism was mediated via downregulation of the bile acid biosynthetic pathway.

Disturbances in the local and peripheral immune systems are closely linked to a wide range of diseases. In the context of neurodegenerative disorders such as Alzheimer's disease (AD), inflammation plays a crucial role, often appearing as a common manifestation despite the variability in the occurrence of other pathophysiological hallmarks. Thus, combating neuroinflammation holds promise in treating complex pathophysiological diseases like AD. Growing evidence suggests the gut microbiome's crucial role in shaping the pathogenesis of AD by influencing inflammatory mediators. Gut dysbiosis can potentially activate neuroinflammatory pathways through bidirectional signaling of the gut-brain axis; however, the precise mechanisms of this complex interweaved network remain largely unclear. In these milieus, this review attempts to summarize the contributing role of gut microbiome-mediated neuroinflammatory signals in AD pathophysiology, while also pondering potential mechanisms through which commensal and pathogenic gut microbes affect neuroinflammation. While certain taxa such as Roseburia and Escherichia have been strongly correlated with AD, other clades such as Bacteroides and Faecalibacterium exhibit variations at the species and strain levels. In order to disentangle the inflammatory aspects of neurodegeneration attributed to the gut microbiome, it is imperative that future mechanistic studies investigate the species/strain-level dependency of commensals, opportunistic, and pathogenic gut microbes that consistently show correlations with AD patients across multiple associative studies.

Alzheimer's disease (AD) is a central nervous system (CNS) degenerative disorder, is caused by various factors including β-amyloid toxicity, hyperphosphorylation of tau protein, oxidative stress, and others. The dysfunction of microglia has been associated with the onset and advancement of different neurodevelopmental and neurodegenerative disorders, such as AD. The gut of mammals harbors a vast and complex population of microorganisms, commonly referred to as the microbiota. There's a growing recognition that these gut microbes are intrinsically intertwined with mammalian physiology. Through the circulation of metabolites, they establish metabolic symbiosis, enhance immune function, and establish communication with different remote cells, including those in the brain. The gut microbiome plays a crucial part in influencing the development and performance of microglia, as indicated by recent preclinical studies. Dysbiosis of the intestinal flora leads to alterations in the microglia transcriptome that regulate the interconversion of microglia subtypes. This conversation explores recent research that clarifies how gut bacteria, their byproducts, and harmful elements affect the activation and characteristics of microglia. This understanding opens doors to innovative microbial-based therapeutic strategies for early identification and treatment goals in AD.

The health of chicks is closely related to their productivity. Yupingfeng polysaccharide (YPF-P) is a kind of water-soluble polysaccharide extracted from Yupingfeng powder; it has high pharmacological activity and can be used as a potential substitute for antibiotics to improve the health of chicks. This study aimed to investigate the effects of YPF-P on immune performance, the duodenum, and the cecal microflora of chicks. All chickens (4224) were randomly distributed into four groups (eight replicas/group, 132 hens/replica). The control group was fed a basal diet (0 g/kg YPF-P), while the experimental groups were fed basal diets supplemented with 1, 2, or 4 g/kg YPF-P. The results showed that YPF-P significantly increased the thymus index (p < 0.05). The content of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), immunoglobulin A (IgA), and IgG and immunoglobulin M (IgM) was upregulated in the serum by YPF-P (p < 0.05). YPF-P decreased the content of malondialdehyde (MDA) (p < 0.05). Further, 16S rRNA sequencing showed that 2 g/kg YPF-P modulated the predominant duodenum and cecal microbial community structure, which increased the number of Faecalibacterium, Megamonas, Bacteroides, Alistipes, NK4A214_group, and Enterococcus. In conclusion, YPF-P ameliorated the growth performance of chicks by regulating serum immune and antioxidant balance, as well as the intestinal microbiota.

Microbiota-gut-brain axis interacts with one another to regulate brain functions. However, whether the impacts of gut dysbiosis on limbic white matter (WM) tracts contribute to the neuropsychiatric symptoms (NPS) in patients with amyloid-positive amnestic mild cognitive impairment (aMCI+), have not been explored yet. This study aimed to investigate the mediation effects of limbic WM integrity on the association between gut microbiota and NPS in patients with aMCI+.

Twenty patients with aMCI + and 20 healthy controls (HCs) were enrolled. All subjects underwent neuropsychological assessments and their microbial compositions were characterized using 16S rRNA Miseq sequencing technique. Amyloid deposition inspected by positron emission tomography imaging and limbic WM tracts (i.e., fornix, cingulum, and uncinate fasciculus) detected by diffusion tensor imaging were additionally measured in patients with aMCI+. We employed a regression-based mediation analysis using Hayes's PROCESS macro in this study.

The relative abundance of genera Ruminococcus and Lactococcus was significantly decreased in patients with aMCI + versus HCs. The relative abundance of Ruminococcus was negatively correlated with affective symptom cluster in the aMCI + group. Notably, this association was mediated by WM integrity of the left cingulate gyrus.

Our findings suggest Ruminococcus as a potential target for the management of affective impairments in patients with aMCI+.

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.

The gut microbiome has been reported to be closely related to Alzheimer's disease (AD) progression. Here, a comprehensive meta-analysis of gut microbial characteristics in AD, mild cognitive impairment (MCI) and subjective cognitive decline (SCD) was performed to compare gut microbial alterations at each stage.

A total of 10 databases (CNKI, WanFang, VIP, SinoMed, WOS, PubMed, Embase, Cochrane Library, PsycINFO and Void) were searched and 34 case-control studies were included. α and β diversity and the relative abundance of gut microbiota were analysed as outcome indices. Data analysis was performed using Review Manager (5.4.1) and R.

Chao1 and Shannon index levels in AD were significantly lower compared with healthy controls (HCs), and the Chao1 index was significantly lower in MCI compared with HCs. There was a significant difference in β diversity of gut microbiomes in patients (SCD, MCI, AD) compared with HCs. The relative abundance of Firmicutes at the phylum level was significantly lower in patients with AD and MCI than HCs. However, the relative abundance of Bacteroidetes at the phylum level was significantly higher in patients with MCI than HCs. There was an increasing trend for Enterobacteriaceae and a decreasing trend for Ruminococcaceae, Lachnospiraceae and Lactobacillus during AD; Lactobacillus showed a decreasing trend early in SCD.

Our results indicated that there were gut microbiological abnormalities in AD, even as early as the SCD stage. The dynamic, consistent changes in gut microbes with the disease process showed that they might serve as potential biomarkers for early identification and diagnosis of AD.