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.

scholarly journals The Potential Role of Polyphenols in Oxidative Stress and Inflammation Induced by Gut Microbiota in Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1370
Author(s):  
Umair Shabbir ◽  
Akanksha Tyagi ◽  
Fazle Elahi ◽  
Simon Okomo Aloo ◽  
Deog-Hwan Oh
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Neurodegenerative Diseases ◽  
Potential Role ◽  
Inflammatory Responses ◽  
Dietary Polyphenols ◽  
Gut Dysbiosis

Gut microbiota (GM) play a role in the metabolic health, gut eubiosis, nutrition, and physiology of humans. They are also involved in the regulation of inflammation, oxidative stress, immune responses, central and peripheral neurotransmission. Aging and unhealthy dietary patterns, along with oxidative and inflammatory responses due to gut dysbiosis, can lead to the pathogenesis of neurodegenerative diseases, especially Alzheimer’s disease (AD). Although the exact mechanism between AD and GM dysbiosis is still unknown, recent studies claim that secretions from the gut can enhance hallmarks of AD by disturbing the intestinal permeability and blood–brain barrier via the microbiota–gut–brain axis. Dietary polyphenols are the secondary metabolites of plants that possess anti-oxidative and anti-inflammatory properties and can ameliorate gut dysbiosis by enhancing the abundance of beneficial bacteria. Thus, modulation of gut by polyphenols can prevent and treat AD and other neurodegenerative diseases. This review summarizes the role of oxidative stress, inflammation, and GM in AD. Further, it provides an overview on the ability of polyphenols to modulate gut dysbiosis, oxidative stress, and inflammation against 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.

Gut microbiota as a link between modern lifestyles and Alzheimer’s disease

2021 ◽  
Vol 14 ◽  
Author(s):  
Yi Wang ◽  
Gary Dykes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Significant Influence ◽  
Therapeutic Strategies ◽  
Future Directions ◽  
Gut Dysbiosis ◽  
Biological Variables ◽  
Modulative Role

: It is established that the gut microbiota has a significant influence on Alzheimer’s disease. In turn, both the disease and the microbiota are affected by biological variables associated with modern lifestyles. The examination of the potential interrelationship among these three factors and on the role played by lifestyles in gut dysbiosis-induced pathologies of Alzheimer’s disease are limited. Deciphering these connections will provide insights into the pathogenesis and therapeutic strategies for Alzheimer’s disease. Specifically, based on this trilateral relationship, various non-pharmacological interventive strategies targeting the gut microbiota can be developed. This review fills this gap by presenting the latest evidence for the modulative role of modern lifestyles on the gut microbiota and its relevance to Alzheimer’s disease, with a discussion on the limitations of current research and future directions.

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 Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 145
Author(s):  
Julio Plaza-Díaz ◽  
Patricio Solis-Urra ◽  
Jerónimo Aragón-Vela ◽  
Fernando Rodríguez-Rodríguez ◽  
Jorge Olivares-Arancibia ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Liver Steatosis ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Current Treatment ◽  
Immune Defense ◽  
Alcoholic Fatty Liver ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

scholarly journals Astrocytes and neuroinflammation in Alzheimer's disease

2014 ◽  
Vol 42 (5) ◽  
pp. 1321-1325 ◽  
Author(s):  
Emma C. Phillips ◽  
Cara L. Croft ◽  
Ksenia Kurbatskaya ◽  
Michael J. O’Neill ◽  
Michael L. Hutton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Inflammatory Responses ◽  
Amyloid Β ◽  
Synaptic Dysfunction ◽  
Amyloid Β Peptide ◽  
Substantial Evidence ◽  
Models Of Disease ◽  
Opposing Effects

Increased production of amyloid β-peptide (Aβ) and altered processing of tau in Alzheimer's disease (AD) are associated with synaptic dysfunction, neuronal death and cognitive and behavioural deficits. Neuroinflammation is also a prominent feature of AD brain and considerable evidence indicates that inflammatory events play a significant role in modulating the progression of AD. The role of microglia in AD inflammation has long been acknowledged. Substantial evidence now demonstrates that astrocyte-mediated inflammatory responses also influence pathology development, synapse health and neurodegeneration in AD. Several anti-inflammatory therapies targeting astrocytes show significant benefit in models of disease, particularly with respect to tau-associated neurodegeneration. However, the effectiveness of these approaches is complex, since modulating inflammatory pathways often has opposing effects on the development of tau and amyloid pathology, and is dependent on the precise phenotype and activities of astrocytes in different cellular environments. An increased understanding of interactions between astrocytes and neurons under different conditions is required for the development of safe and effective astrocyte-based therapies for AD and related neurodegenerative diseases.

scholarly journals Lupus Gut Microbiota Transplants Cause Autoimmunity and Inflammation

2021 ◽  
Author(s):  
Yiyangzi Ma ◽  
Ruru Guo ◽  
Yiduo Sun ◽  
Xin Li ◽  
Lun He ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Lupus Erythematosus ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Healthy Controls ◽  
Germ Free ◽  
Autoimmune Antibodies ◽  
Expression Of Genes ◽  
Rdna Sequencing

Background: The etiology of systemic lupus erythematosus (SLE) is multifactorial. Recently, growing evidence suggests that the microbiota plays a role in SLE, yet whether gut microbiota participates in the development of SLE remains largely unknown. To investigate this issue, we carried out 16s rDNA sequencing analyses in a cohort of 18 female un-treated active SLE patients and 7 female healthy controls, and performed fecal microbiota transplantation from patients and healthy controls to germ-free mice. Results: Compared to the healthy controls, we found no significant different microbial diversity but some significantly different species in SLE patients including Turicibacter genus and other 5 species. Fecal transfer from SLE patients to germ free (GF) C57BL/6 mice caused GF mice to develop a series of lupus-like phenotyptic features, which including an increased serum autoimmune antibodies, and imbalanced cytokines, altered distribution of immune cells in mucosal and peripheral immune response, and upregulated expression of genes related to SLE in recipient mice that received SLE fecal microbiota transplantation (FMT). Moreover, the metabolism of histidine was significantly altered in GF mice treated with SLE patient feces, as compared to those which received healthy fecal transplants. Conclusions: Overall, our results describe a causal role of aberrant gut microbiota in contributing to the pathogenesis of SLE. The interplay of gut microbial and histidine metabolism may be one of the mechanisms intertwined with autoimmune activation in SLE.

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