scholarly journals Disturbed microbial ecology in Alzheimer’s disease: evidence from the gut microbiota and fecal metabolome

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jianxiong Xi ◽  
Ding Ding ◽  
Huiwei Zhu ◽  
Ruru Wang ◽  
Feng Su ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Fecal Microbiota ◽  
Gene Profiling ◽  
Microbial Composition ◽  
Non Invasive ◽  
Fecal Markers ◽  
Ultrahigh Performance Liquid Chromatography ◽  
Metabolic Output

Abstract Background Gut microbiota (GMB) alteration has been reported to influence the Alzheimer’s disease (AD) pathogenesis through immune, endocrine, and metabolic pathways. This study aims to investigate metabolic output of the dysbiosis of GMB in AD pathogenesis. In this study, the fecal microbiota and metabolome from 21 AD participants and 44 cognitively normal control participants were measured. Untargeted GMB taxa was analyzed through 16S ribosomal RNA gene profiling based on next-generation sequencing and fecal metabolites were quantified by using ultrahigh performance liquid chromatography-mass spectrometry (UPLC-MS). Results Our analysis revealed that AD was characterized by 15 altered gut bacterial genera, of which 46.7% (7/15 general) was significantly associated with a series of metabolite markers. The predicted metabolic profile of altered gut microbial composition included steroid hormone biosynthesis, N-Acyl amino acid metabolism and piperidine metabolism. Moreover, a combination of 2 gut bacterial genera (Faecalibacterium and Pseudomonas) and 4 metabolites (N-Docosahexaenoyl GABA, 19-Oxoandrost-4-ene-3,17-dione, Trigofoenoside F and 22-Angeloylbarringtogenol C) was able to discriminate AD from NC with AUC of 0.955 in these 65 subjects. Conclusions These findings demonstrate that gut microbial alterations and related metabolic output changes may be associated with pathogenesis of AD, and suggest that fecal markers might be used as a non-invasive examination to assist screening and diagnosis of AD.

scholarly journals Crosstalk between Gut and Brain in Alzheimer’s Disease: The Role of Gut Microbiota Modulation Strategies

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 690
Author(s):  
Umair Shabbir ◽  
Muhammad Sajid Arshad ◽  
Aysha Sameen ◽  
Deog-Hwan Oh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Dietary Habits ◽  
Inflammatory Responses ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Gut Dysbiosis ◽  
Dynamic Population

The gut microbiota (GM) represents a diverse and dynamic population of microorganisms and about 100 trillion symbiotic microbial cells that dwell in the gastrointestinal tract. Studies suggest that the GM can influence the health of the host, and several factors can modify the GM composition, such as diet, drug intake, lifestyle, and geographical locations. Gut dysbiosis can affect brain immune homeostasis through the microbiota–gut–brain axis and can play a key role in the pathogenesis of neurodegenerative diseases, including dementia and Alzheimer’s disease (AD). The relationship between gut dysbiosis and AD is still elusive, but emerging evidence suggests that it can enhance the secretion of lipopolysaccharides and amyloids that may disturb intestinal permeability and the blood–brain barrier. In addition, it can promote the hallmarks of AD, such as oxidative stress, neuroinflammation, amyloid-beta formation, insulin resistance, and ultimately the causation of neural death. Poor dietary habits and aging, along with inflammatory responses due to dysbiosis, may contribute to the pathogenesis of AD. Thus, GM modulation through diet, probiotics, or fecal microbiota transplantation could represent potential therapeutics in AD. In this review, we discuss the role of GM dysbiosis in AD and potential therapeutic strategies to modulate GM in AD.

Non-uinform gut microbiota alteration patterns associated with therapeutic outcomes in an Alzheimer's disease animal model

2019 ◽  
Author(s):  
Min Wang ◽  
William Kwame Amakye ◽  
Jianing Cao ◽  
Congcong Gong ◽  
Xiaoyu Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Therapeutic Outcomes ◽  
Targeted Treatments ◽  
Amyloid Aβ

Abstract Background: Dysbiosis of gut microbiota is associated with the progression of beta-amyloid (Aβ) pathology in Alzheimer’s disease (AD). We aimed to identify uniform Aβ-responsible gut microbiota status as possible guideline for gut microbiota manipulation and the prediction of outcomes of microbiota targeted treatments. Six months old APP/PS1 mice from the same genetic background, housing and feeding conditions were then daily gavage with Metformin, peptides WN5 or PW5 to manipulate the gut microbiota for 12 weeks. Aβ pathology and gut microbiota were then explored and compared. Results: Fecal microbiota transplantation (FMT) from a 16 month old APP/PS1 mouse reconstituted the gut microbiota towards the donor and increased Aβ pathology in APP/PS1 mouse model. Metformin, peptides WN5 and PW5 all attenuated Aβ-plaque formation in APP/PS1 mouse model but each was associated with distinct gut microbiota status. No uniform gut microbiota pattern associated with Aβ pathology was found among different gut microbiota-targeted treatments. Conclusion: We found no uniform gut microbiota status associated with Aβ pathology suggesting gut microbiota status is not a suitable biomarker for AD diagnosis and treatment predictions. Alteration of gut microbiota in itself may not be sufficiently directly related to functional outcomes and might only be a shadow of deeper molecular mechanisms not fully understood. The findings here strongly suggested that the significance of gut microbiota alteration in disease pathology and treatment may have so far been over claimed and that interpretation of gut microbiota data should be done with utmost caution.

Gut Microbiota Changes and Their Correlation with Cognitive and Neuropsychiatric Symptoms in Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Yunzhe Zhou ◽  
Yan Wang ◽  
Meina Quan ◽  
Huiying Zhao ◽  
Jianping Jia
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Ribosomal Rna ◽  
Neuropsychiatric Symptoms ◽  
Clinical Dementia Rating ◽  
Microbial Composition ◽  
Healthy Control ◽  
And Behavior ◽  
State Examination

Background: Gut microbiota can influence human brain function and behavior. Recent studies showed that gut microbiota might play an important role in the pathogenesis of Alzheimer’s disease (AD). Objective: To investigate the composition of gut microbiota in AD patients and their association with cognitive function and neuropsychiatric symptoms (NPS). Methods: The fecal samples from 60 AD patients (30 with NPS and 30 without NPS) and 32 healthy control subjects (HC) were collected and analyzed by 16S ribosomal RNA sequencing. The functional variations of gut microbiota were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. The correlation between different bacterial taxa and cognitive (Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR)), and NPS measures were analyzed. Results: The fecal microbial composition of AD patients was quite distinct from HC. Bifidobacterium, Sphingomonas, Lactobacillus, and Blautia were enriched, while Odoribacter, Anaerobacterium, and Papillibacter were reduced. AD patients with NPS showed decreased Chitinophagaceae, Taibaiella, and Anaerobacterium compared with those without NPS. Functional pathways were different between AD and HC, and between AD patients with and without NPS. Correlation analysis showed that Sphingomonas correlated negatively with MMSE; Anaerobacterium and Papillibacter correlated positively with MMSE and negatively with CDR. Cytophagia, Rhodospirillaceae, and Cellvibrio correlated positively with NPS, while Chitinophagaceae, Taibaiella, and Anaerobacterium correlated negatively with NPS. Conclusion: AD patients have gut microbiota alterations related to cognition, and differential taxa between AD patients with and without NPS associated differently with NPS domains, which helps further understand the pathogenesis of AD and explore potential therapeutic targets.

scholarly journals Do the Bugs in Your Gut Eat Your Memories? Relationship between Gut Microbiota and Alzheimer’s Disease

2020 ◽  
Vol 10 (11) ◽  
pp. 814
Author(s):  
Emily M. Borsom ◽  
Keehoon Lee ◽  
Emily K. Cope
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Dietary Intervention ◽  
Fecal Microbiota Transplantation ◽  
Neurological Diseases ◽  
Amyloid Β ◽  
Reproductive Organs ◽  
Fecal Microbiota ◽  
Autism Spectrum

The human microbiota is composed of trillions of microbial cells inhabiting the oral cavity, skin, gastrointestinal (GI) tract, airways, and reproductive organs. The gut microbiota is composed of dynamic communities of microorganisms that communicate bidirectionally with the brain via cytokines, neurotransmitters, hormones, and secondary metabolites, known as the gut microbiota–brain axis. The gut microbiota–brain axis is suspected to be involved in the development of neurological diseases, including Alzheimer’s disease (AD), Parkinson’s disease, and Autism Spectrum Disorder. AD is an irreversible, neurodegenerative disease of the central nervous system (CNS), characterized by amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Microglia and astrocytes, the resident immune cells of the CNS, play an integral role in AD development, as neuroinflammation is a driving factor of disease severity. The gut microbiota–brain axis is a novel target for Alzheimer’s disease therapeutics to modulate critical neuroimmune and metabolic pathways. Potential therapeutics include probiotics, prebiotics, fecal microbiota transplantation, and dietary intervention. This review summarizes our current understanding of the role of the gut microbiota–brain axis and neuroinflammation in the onset and development of Alzheimer’s disease, limitations of current research, and potential for gut microbiota–brain axis targeted therapies.

scholarly journals Structural and Functional Dysbiosis of Fecal Microbiota in Chinese Patients With Alzheimer's Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Zongxin Ling ◽  
Manlian Zhu ◽  
Xiumei Yan ◽  
Yiwen Cheng ◽  
Li Shao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fecal Microbiota ◽  
Taxonomic Composition ◽  
Chinese Patients ◽  
Rrna Gene ◽  
Clinical Indicators ◽  
Non Invasive ◽  
Gut Dysbiosis ◽  
And Gender

Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of gut–brain disorders, such as Alzheimer's disease (AD). However, alterations of the gut microbiota as well as their correlations with cognitive scores and host immunity have remained unclear in well-controlled trials on Chinese AD patients. In this study, samples from 100 AD patients, and 71 age- and gender-matched, cognitively normal controls were obtained to explore the structural and functional alterations of the fecal microbiota targeting the V3–V4 region of the 16S rRNA gene by MiSeq sequencing, and to analyze their associations with clinical characteristics. Our data demonstrated a remarkably reduction in the bacterial diversity and alterations in the taxonomic composition of the fecal microbiota of the AD patients. Interestingly, the abundant butyrate-producing genera such as Faecalibacterium decreased significantly, where this was positively correlated with such clinical indicators as the MMSE, WAIS, and Barthel scores in the AD patients. On the contrary, abundant lactate-producing genera, such as Bifidobacterium, increased prominently, and were inversely correlated with these indicators. This shift in the gut dysbiosis of the microbiota, from being butyrate producers to lactate producers, contributed to immune disturbances in the host that could be used as non-invasive biomarkers to distinguish the controls from the AD patients. Moreover, several predicted functional modules, including the biosynthesis and the metabolism of fatty acids, that were altered in the microbiota of the AD patients could be utilized by the bacteria to produce immunomodulatory metabolites. Our study established the structural and functional dysbiosis of fecal microbiota in AD patients, and the results suggest the potential for use of gut bacteria for the early, non-invasive diagnosis of AD, personalized treatment, and the development of tailor-made probiotics designed for Chinese AD patients.

scholarly journals Fecal microbiota transplantation derived from Alzheimer's disease mice worsens brain trauma outcomes in young C57BL/6 mice

2021 ◽  
Author(s):  
Sirena Soriano ◽  
Kristen Curry ◽  
Qi Wang ◽  
Elsbeth Chow ◽  
Todd Treangen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune System ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Immunohistochemical Analysis ◽  
Fecal Microbiota ◽  
Motor Recovery ◽  
Neurological Deficits

Traumatic brain injury (TBI) cause neuroinflammation, exaggerated immune response, and, consequently, neurodegeneration. The gut microbiome is an essential modulator of the immune system, impacting in the brain. There are not effective treatments for TBI, therefore, modulating the gut microbiome may shed novel therapeutics for the damaged brain. Also, in patients with Alzheimer's disease (AD), the microbiota has been associated with a lack of diversity, which negatively modulates the immune system. This study aimed to determine whether the gut microbiota from AD mice exacerbates neurological deficits after TBI in young mice. For this purpose, we performed fecal microbiota transplants from AD (FMT-AD) mice into young C57BL/6 (wild-type, WT) mice following TBI. Thus, FMT-AD and fecal microbiota transplants from healthy controls (FMT-young) were administered orally to young WT mice after the TBI occurred. We first determined the gut microbiota diversity and composition by analyzing full-length 16S rRNA sequences from mouse fecal samples using the Oxford Nanopore MinION technology. We collected the blood, brain, and gut tissues for protein and immunohistochemical analysis. Our results showed that FMT-AD treatment stimulates a higher relative abundance of Muribaculum intestinal and a decrease in Lactobacillus johnsonii compared FMT-young treatment in WT mice. Furthermore, WT mice exhibited larger lesion volumes, increased the number of activated microglia/macrophages cells, and reduced motor recovery after FMT-AD compared to FMT-young one day after TBI. Thus, the gut microbiota from AD mice not only aggravates the neuroinflammatory response and motor recovery, but also increases the lesion size after TBI in young WT mice.

scholarly journals Gut Microbiota and Dysbiosis in Alzheimer’s Disease: Implications for Pathogenesis and Treatment

2020 ◽  
Vol 57 (12) ◽  
pp. 5026-5043 ◽  
Author(s):  
Shan Liu ◽  
Jiguo Gao ◽  
Mingqin Zhu ◽  
Kangding Liu ◽  
Hong-Liang Zhang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Gut Dysbiosis ◽  
Bidirectional Communication ◽  
Significant Research ◽  
Novel Therapeutic Strategies ◽  
The Brain ◽  
Brain Homeostasis ◽  
Gut Microbiota Composition

Abstract Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term “microbiota-gut-brain axis” from “gut-brain axis” underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer’s disease (AD). Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.

scholarly journals Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Öhman ◽  
Anders Lasson ◽  
Anna Strömbeck ◽  
Stefan Isaksson ◽  
Marcus Hesselmar ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Disease Activity ◽  
Temporal Dynamics ◽  
Fecal Microbiota ◽  
Disease Stage ◽  
Dietary Interventions ◽  
Microbial Composition ◽  
Fecal Samples ◽  
Specific Species

AbstractPatients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2–6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3–10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

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