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 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.

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 Rapid improvement in Alzheimer’s disease symptoms following fecal microbiota transplantation: a case report

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092593
Author(s):  
Sabine Hazan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Memory Loss ◽  
Amyloid Β ◽  
Fecal Microbiota ◽  
Symptom Improvement ◽  
Amyloid Β Peptide ◽  
Rapid Improvement

Alzheimer’s disease (AD), the most common form of dementia, is a leading cause of death and a major cause of morbidity in older people. The disease is characterized by progressive memory loss, cognitive impairment, and the cerebral accumulation of amyloid-β peptide. Given the health and economic impacts of AD, treatments that target the underlying etiology of AD or modify the course of the disease are of significant interest. The gut microbiome has been increasingly implicated in the pathogenesis of several neurological diseases, including multiple sclerosis and Parkinson’s disease. Furthermore, emerging evidence has demonstrated that there are alterations in gut microbiome composition in patients with AD, suggesting involvement of the microbiome–gut–brain axis. We present symptom improvement in a patient with AD following fecal microbiota transplantation for a Clostridioides difficile infection.

scholarly journals The Gut Microbiota in Multiple Sclerosis: An Overview of Clinical Trials

2019 ◽  
Vol 28 (12) ◽  
pp. 1507-1527 ◽  
Author(s):  
Giovanni Schepici ◽  
Serena Silvestro ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Multiple Sclerosis ◽  
Immune System ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
System A ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Review Reports

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and degenerative disease that affects the central nervous system. A recent study showed that interaction between the immune system and the gut microbiota plays a crucial role in the development of MS. This review reports the clinical studies carried out in recent years that aimed to evaluate the composition of the microbiota in patients with relapsing–remitting MS (RR-MS). We also report what is available in the literature regarding the effectiveness of fecal microbiota transplantation and the role of the diet in restoring the intestinal bacterial population. Studies report that patients with RR-MS have a microbiota that, compared with healthy controls, has higher amounts of Pedobacteria, Flavobacterium, Pseudomonas, Mycoplana, Acinetobacter, Eggerthella, Dorea, Blautia, Streptococcus and Akkermansia. In contrast, MS patients have a microbiota with impoverished microbial populations of Prevotella, Bacteroides, Parabacteroides, Haemophilus, Sutterella, Adlercreutzia, Coprobacillus, Lactobacillus, Clostridium, Anaerostipes and Faecalibacterium. In conclusion, the restoration of the microbial population in patients with RR-MS appears to reduce inflammatory events and the reactivation of the immune system.

scholarly journals The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiangjun Liu ◽  
Ye Cheng ◽  
Dan Zang ◽  
Min Zhang ◽  
Xiuhua Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Checkpoint Inhibitors ◽  
Fecal Microbiota ◽  
Immune Homeostasis ◽  
Gut Dysbiosis ◽  
Underlying Mechanisms ◽  
And Function

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.

scholarly journals Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Donglin Du ◽  
Wei Tang ◽  
Chao Zhou ◽  
Xiaochuan Sun ◽  
Zhengqiang Wei ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Methionine Sulfoxide Reductase ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Rat Serum ◽  
Gut Microbiota Dysbiosis

Background. Traumatic brain injury (TBI) can induce persistent fluctuation in the gut microbiota makeup and abundance. The present study is aimed at determining whether fecal microbiota transplantation (FMT) can rescue microbiota changes and ameliorate neurological deficits after TBI in rats. Methods. A controlled cortical impact (CCI) model was used to simulate TBI in male Sprague-Dawley rats, and FMT was performed for 7 consecutive days. 16S ribosomal RNA (rRNA) sequencing of fecal samples was performed to analyze the effects of FMT on gut microbiota. Modified neurological severity score and Morris water maze were used to evaluate neurobehavioral functions. Metabolomics was used to screen differential metabolites from the rat serum and ipsilateral brains. The oxidative stress indices were measured in the brain. Results. TBI induced significance changes in the gut microbiome, including the alpha- and beta-bacterial diversity, as well as the microbiome composition at 8 days after TBI. On the other hand, FMT could rescue these changes and relieve neurological deficits after TBI. Metabolomics results showed that the level of trimethylamine (TMA) in feces and the level of trimethylamine N-oxide (TMAO) in the ipsilateral brain and serum was increased after TBI, while FMT decreased TMA levels in the feces, and TMAO levels in the ipsilateral brain and serum. Antioxidant enzyme methionine sulfoxide reductase A (MsrA) in the ipsilateral hippocampus was decreased after TBI but increased after FMT. In addition, FMT elevated SOD and CAT activities and GSH/GSSG ratio and diminished ROS, GSSG, and MDA levels in the ipsilateral hippocampus after TBI. Conclusions. FMT can restore gut microbiota dysbiosis and relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI.

Gut microbiota regulate Alzheimer’s disease pathologies and cognitive disorders via PUFA-associated neuroinflammation

Gut ◽  
2022 ◽  
pp. gutjnl-2021-326269
Author(s):  
Chun Chen ◽  
Jianming Liao ◽  
Yiyuan Xia ◽  
Xia Liu ◽  
Rheinallt Jones ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Amyloid Β ◽  
Microglia Activation ◽  
Oxidative Enzymes ◽  
Dependent Manner ◽  
Germ Free ◽  
Healthy Donors

ObjectiveThis study is to investigate the role of gut dysbiosis in triggering inflammation in the brain and its contribution to Alzheimer’s disease (AD) pathogenesis.DesignWe analysed the gut microbiota composition of 3×Tg mice in an age-dependent manner. We generated germ-free 3×Tg mice and recolonisation of germ-free 3×Tg mice with fecal samples from both patients with AD and age-matched healthy donors.ResultsMicrobial 16S rRNA sequencing revealed Bacteroides enrichment. We found a prominent reduction of cerebral amyloid-β plaques and neurofibrillary tangles pathology in germ-free 3×Tg mice as compared with specific-pathogen-free mice. And hippocampal RNAseq showed that inflammatory pathway and insulin/IGF-1 signalling in 3×Tg mice brain are aberrantly altered in the absence of gut microbiota. Poly-unsaturated fatty acid metabolites identified by metabolomic analysis, and their oxidative enzymes were selectively elevated, corresponding with microglia activation and inflammation. AD patients’ gut microbiome exacerbated AD pathologies in 3×Tg mice, associated with C/EBPβ/asparagine endopeptidase pathway activation and cognitive dysfunctions compared with healthy donors’ microbiota transplants.ConclusionsThese findings support that a complex gut microbiome is required for behavioural defects, microglia activation and AD pathologies, the gut microbiome contributes to pathologies in an AD mouse model and that dysbiosis of the human microbiome might be a risk factor for AD.

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