Surgery-induced gut microbial dysbiosis promotes cognitive impairment via regulation of intestinal function and the metabolite palmitic amide

Microbiome, Год журнала: 2023, Номер 11(1)

Опубликована: Ноя. 8, 2023

Perioperative neurocognitive disorders (PND) are the most common postoperative complications with few therapeutic options. Gut microbial dysbiosis is associated neurological diseases; however, mechanisms by which microbiota regulates gastrointestinal and cognitive function incompletely understood.Behavioral testing, MiSeq 16S rRNA gene sequencing, non-target metabolism, intestinal permeability detection, protein assays, immunofluorescence staining were employed to discern impacts of surgery on profiles, barriers, serum brain. Interventions in mice included fecal transplantation, anti-inflammatory agent dexamethasone, Lactobacillus supplementation, indole propionic acid palmitic amide administration.Surgery-induced impairment occurs predominantly aged mice, surgery-induced alterations composition profile exacerbate barrier disruption mice. These adverse effects can be mitigated transferring from young donors or bolstering using Lactobacillus, acid. Moreover, profiles restored transplanting feces surgical improving neuropathology function, these coincide increased permeability. Metabolomic screening identified metabolites mouse after surgery, especially increase amide. Palmitic levels brain decreased Oral exacerbates neuropathological changes mice.Gut a key mechanism leading cognition dysfunction, disrupts metabolic abnormalities, resulting neuroinflammation dendritic spine loss. Intestinal damage high level old may cause incidence PND elderly. Preoperative regulation restoration benefit preventing PND. Video Abstract.

Язык: Английский

---

Prophylactic Administration of Gut Microbiome Metabolites Abrogated Microglial Activation and Subsequent Neuroinflammation in an Experimental Model of Japanese Encephalitis

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(8), С. 1712 - 1727

Опубликована: Апрель 6, 2024

Short-chain fatty acids (SCFAs) are gut microbial metabolic derivatives produced during the fermentation of ingested complex carbohydrates. SCFAs have been widely regarded to a potent anti-inflammatory and neuro-protective role implications in several disease conditions, such as, inflammatory bowel disease, type-2 diabetes, neurodegenerative disorders. Japanese encephalitis virus (JEV), neurotropic flavivirus, is associated with life threatening neuro-inflammation neurological sequelae infected hosts. In this study, we hypothesize that potential mitigating JEV pathogenesis. Postnatal day 10 BALB/c mice were intraperitoneally injected either SCFA mixture (acetate, propionate, butyrate) or PBS for period 7 days, followed by infection. All observed onset progression symptoms. The brain tissue was collected upon reaching terminal illness further analysis. SCFA-supplemented JEV-infected (SCFA + JEV) showed delayed symptoms, lower hindlimb clasping score, decreased weight loss increased survival 3 days (p < 0.0001) infection as opposed PBS-treated animals (JEV). Significant downregulation cytokines TNF-α, MCP-1, IL-6, IFN-Υ group relative control observed. Inflammatory mediators, phospho-NF-kB (P-NF-kB) iba1, 2.08 ± 0.1 3.132 0.43-fold upregulation versus 1.19 0.11 1.31 0.11-fold group, respectively. Tissue section analysis exhibited reduced glial activation (JEV group─42 2.15 microglia/ROI; group─27.07 1.8 microglia/ROI) received supplementation prior seen from astrocytic microglial morphometric Caspase-3 immunoblotting 4.08 1.3-fold compared 1.03 0.14-fold TUNEL assay cellular death post-JEV (JEV-6.4 1.5 cells/ROI JEV-3.7 0.73 cells/ROI). Our study critically contributes increasing evidence support an agent, expand its scope supplementary intervention JEV-mediated neuroinflammation.

Язык: Английский

---

The Role of Short-Chain Fatty Acids and Altered Microbiota Composition in Autism Spectrum Disorder: A Comprehensive Literature Review

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(24), С. 17432 - 17432

Опубликована: Дек. 13, 2023

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in communication and social interactions, restrictive repetitive behavior, wide range of cognitive impediments. The prevalence ASD tripled the last 20 years now affects 1 44 children. Although ASD's etiology not yet elucidated, growing body evidence shows that it stems from interplay genetic environmental factors. In recent years, there has been increased focus on role gut microbiota their metabolites, as studies show patients significant shift composition, an increase specific bacteria elevated levels short-chain fatty acids (SCFAs), especially propionic acid (PPA). This review aims to provide overview SCFAs human body, well possible implications shift. Also, highlights current aiming compare composition microbiome ASD-afflicted with neurotypical control. Finally, rodents where ASD-like symptoms or molecular hallmarks are evoked, via grafting microbes obtained subjects direct exposure PPA.

Язык: Английский

---

Inflammatory Manifestations Associated With Gut Dysbiosis in Alzheimer’s Disease

International Journal of Alzheimer s Disease, Год журнала: 2024, Номер 2024(1)

Опубликована: Янв. 1, 2024

Recent studies strongly suggest that gut microbiome can influence brain functions and contribute to the development of Alzheimer’s disease (AD). However, reported changes in microbiomes AD patients from different countries are not similar, more research is needed reveal relationships between human diverse ethnic populations. There also an assumption microbiome‐associated peripheral inflammation might drive sporadic AD. This cross‐sectional study aimed at analyzing microbial profile exploring potential associations with blood cytokines some clinical parameters among individuals diagnosed Kazakhstan. Consistent previous studies, we have found landscape reveals specific alterations microbiome. Specifically, patient group showed a decreased Firmicutes/Bacteroidetes ratio. The differential abundance analysis highlighted dysbiosis microbiota patients, marked by reduced presence Bifidobacterium , particularly B. breve . In our study, patients’ altered composition notably features increased Pseudomonadota like Phyllobacterium inflammatory bacteria such as Synergistetes Christensenellaceae family. metabolic profiling predominant pathways related sugar, carrier molecules, tetrapyrrole, pyrimidine biosynthesis, nucleic acid processing. reduction SCFA, carbohydrate, polysaccharide, polyamine, myo‐inositol degradation pathways. increases proinflammatory IL‐1a, IL‐8, IL‐17A, IL‐12p40, TNF‐ β MCP‐1, IL‐2, IL‐12p70 anti‐inflammatory IL‐10 IL‐13 were observed patients. Key variables driving separation controls include markers (IL‐1a IL‐8), growth factors (EGF), lipids (LDL), BMI, microbes, genus Tyzzerella Turicibacter species Parabacteroides distasonis Bacteroides eggerthii We demonstrated almost all correlate serum adiponectin levels taxa Thus, findings identify signatures ethnically distinct cohort These could serve biomarkers microbiota‐based therapeutic targets for treating

Язык: Английский

---

Pharmacological effects of herbal ingredients of Manasamitra vatakam in the treatment of Alzheimer's disease: A review

Journal of Ayurveda and Integrative Medicine, Год журнала: 2025, Номер 16(1), С. 101041 - 101041

Опубликована: Янв. 1, 2025

Multi-targeted drug therapy has received substantial attention for the treatment of diseases multi-factorial origin, including neurodegenerative and autoimmune diseases. It seems reasonable to argue that complex pathology (ND) cannot be reduced a single target modulate broad range cellular signaling, associated pathologies, symptoms. is this idea brought scientific world towards phytochemicals traditional drugs are notoriously multi-targeted. A systematic study these formulations establishing molecular pathways individual molecules can lead standardized multi-component product activities on different targets ND. This could provide an accessible affordable solution significant disease burden With in mind, review was carried out Ayurvedic Manasamitra Vatakam (MMV), known neuroprotective formulation highly effective against Alzheimer's disease. MMV source phytomolecules treating The multifactorial nature makes them suitable candidates testing due inherent multitargeting capabilities compounds. primary objective comprehensive understanding from responsible its multitargeted effect From reported literature, it clear many phytoconstituents extracts herbal ingredients have demonstrated their efficacy AD models. However, combination models never been tested. Scientific studies should done explore bioactive compounds druggability identified evaluated using experimental methods.

Язык: Английский

---