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Gut Microbiota in Cognition, Behaviour and Alzheimer's Disease

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutrition and Public Health".

Deadline for manuscript submissions: closed (25 May 2021) | Viewed by 97800

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Special Issue Editor

Dr. Tanya T. Nguyen

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Guest Editor

Stein Institute for Research on Aging, Department of Psychiatry, University of California San Diego School of Medicine, CA 92093, USA
Interests: gut microbiome; cognition; neuropsychiatric disorders; schizophrenia; Alzheimer’s disease; mental illness; inflammation; cardiometabolic dysfunction

Special Issue Information

Dear Colleagues,

A rapidly growing body of scientific evidence supports the role of the gut microbiome in human health and disease. Its impact extends beyond the gastrointestinal ecosystem and interacts with the central nervous system through the microbiota–gut–brain axis, a complex bidirectional network that is connected via neural, immune, endocrine, and metabolic pathways. Changes in gut microbiota composition and function have been associated with a wide range of neurological and neuropsychiatric disorders, including Alzheimer’s disease (AD) and other cognitive disorders/dementias. While genetic risk clearly plays an important role in Alzheimer’s disease, it is also important to note that the gut microbiome might contribute to or interact with other medical or lifestyle factors that could impact disease pathogenesis and prognosis. This Special Issue will highlight recent research on the role of the gut microbiota on brain and cognitive/behavioral function and the implications for AD and other neurodegenerative disorders. We invite submissions that use next-generation sequencing, metagenomics, and metabolomics, to extend our understanding of the role of the gut microbiome and/or their products in AD. Studies using animal models and human analysis or intervention are welcome, including investigations describing the effects of probiotics, prebiotics, nutrition, and other treatments which modulate gut microbial populations.

Dr. Tanya T. Nguyen
Guest Editor

Manuscript Submission Information

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Keywords

gut microbiome/microbiota
cognition/brain/behavior
Alzheimer’s disease/neurodegenerative disorders/dementia
metabolome
probiotics/prebiotics/nutrition

Published Papers (6 papers)

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Research

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15 pages, 12353 KiB

Open AccessArticle

Altered Gut Microbial Metabolites in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: Signals in Host–Microbe Interplay

by Li Wu, Yuqiu Han, Zhipeng Zheng, Guoping Peng, Ping Liu, Siqing Yue, Shuai Zhu, Jun Chen, Hanying Lv, Lifang Shao, Yan Sheng, Yulan Wang, Liang Li, Lanjuan Li and Baohong Wang

Nutrients 2021, 13(1), 228; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13010228 - 14 Jan 2021

Cited by 104 | Viewed by 9491

Abstract

Intimate metabolic host–microbiome crosstalk regulates immune, metabolic, and neuronal response in health and disease, yet remains untapped for biomarkers or intervention for disease. Our recent study identified an altered microbiome in patients with pre-onset amnestic mild cognitive impairment (aMCI) and dementia Alzheimer’s disease (AD). Thus, we aimed to characterize the gut microbial metabolites among AD, aMCI, and healthy controls (HC). Here, a cohort of 77 individuals (22 aMCI, 27 AD, and 28 HC) was recruited. With the use of liquid-chromatography/gas chromatography mass spectrometry metabolomics profiling, we identified significant differences between AD and HC for tryptophan metabolites, short-chain fatty acids (SCFAs), and lithocholic acid, the majority of which correlated with altered microbiota and cognitive impairment. Notably, tryptophan disorders presented in aMCI and SCFAs decreased progressively from aMCI to AD. Importantly, indole-3-pyruvic acid, a metabolite from tryptophan, was identified as a signature for discrimination and prediction of AD, and five SCFAs for pre-onset and progression of AD. This study showed fecal-based gut microbial signatures were associated with the presence and progression of AD, providing a potential target for microbiota or dietary intervention in AD prevention and support for the host–microbe crosstalk signals in AD pathophysiology. Full article

(This article belongs to the Special Issue Gut Microbiota in Cognition, Behaviour and Alzheimer's Disease)

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Review

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21 pages, 735 KiB

Open AccessEditor’s ChoiceReview

Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders

by Yijing Chen, Jinying Xu and Yu Chen

Nutrients 2021, 13(6), 2099; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13062099 - 19 Jun 2021

Cited by 222 | Viewed by 30958

Abstract

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among the metabolic, peripheral immune, and central nervous systems via the microbiota–gut–brain axis. However, it is not well understood how the gut microbiome and neurons in the brain mutually interact or how these interactions affect normal brain functioning and cognition. We summarize the mechanisms whereby the gut microbiota regulate the production, transportation, and functioning of neurotransmitters. We also discuss how microbiome dysbiosis affects cognitive function, especially in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Full article

(This article belongs to the Special Issue Gut Microbiota in Cognition, Behaviour and Alzheimer's Disease)

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23 pages, 1135 KiB

Open AccessReview

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

by Umair Shabbir, Muhammad Sajid Arshad, Aysha Sameen and Deog-Hwan Oh

Nutrients 2021, 13(2), 690; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020690 - 21 Feb 2021

Cited by 92 | Viewed by 13786

Abstract

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. Full article

(This article belongs to the Special Issue Gut Microbiota in Cognition, Behaviour and Alzheimer's Disease)

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34 pages, 5444 KiB

Open AccessEditor’s ChoiceReview

The Immunopathogenesis of Alzheimer’s Disease Is Related to the Composition of Gut Microbiota

by Friedrich Leblhuber, Daniela Ehrlich, Kostja Steiner, Simon Geisler, Dietmar Fuchs, Lukas Lanser and Katharina Kurz

Nutrients 2021, 13(2), 361; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13020361 - 25 Jan 2021

Cited by 65 | Viewed by 12425

Abstract

The microbiota–gut–brain axis plays an important role in the development of neurodegenerative diseases. Commensal and pathogenic enteric bacteria can influence brain and immune system function by the production of lipopolysaccharides and amyloid. Dysbiosis of the intestinal microbiome induces local and consecutively systemic immune-mediated inflammation. Proinflammatory cytokines then trigger neuroinflammation and finally neurodegeneration. Immune-mediated oxidative stress can lead to a deficiency of vitamins and essential micronutrients. Furthermore, the wrong composition of gut microbiota might impair the intake and metabolization of nutrients. In patients with Alzheimer’s disease (AD) significant alterations of the gut microbiota have been demonstrated. Standard Western diet, infections, decreased physical activity and chronic stress impact the composition and diversity of gut microbiota. A higher abundancy of “pro-inflammatory” gut microbiota goes along with enhanced systemic inflammation and neuroinflammatory processes. Thus, AD beginning in the gut is closely related to the imbalance of gut microbiota. Modulation of gut microbiota by Mediterranean diet, probiotics and curcumin can slow down cognitive decline and alter the gut microbiome significantly. A multi-domain intervention approach addressing underlying causes of AD (inflammation, infections, metabolic alterations like insulin resistance and nutrient deficiency, stress) appears very promising to reduce or even reverse cognitive decline by exerting positive effects on the gut microbiota. Full article

(This article belongs to the Special Issue Gut Microbiota in Cognition, Behaviour and Alzheimer's Disease)

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12 pages, 995 KiB

Open AccessReview

Niacin and Butyrate: Nutraceuticals Targeting Dysbiosis and Intestinal Permeability in Parkinson’s Disease

by Tennekoon B. Karunaratne, Chijioke Okereke, Marissa Seamon, Sharad Purohit, Chandramohan Wakade and Amol Sharma

Nutrients 2021, 13(1), 28; https://0-doi-org.brum.beds.ac.uk/10.3390/nu13010028 - 23 Dec 2020

Cited by 22 | Viewed by 11042

Abstract

Dysbiosis is implicated by many studies in the pathogenesis of Parkinson’s disease (PD). Advances in sequencing technology and computing have resulted in confounding data regarding pathogenic bacterial profiles in conditions such as PD. Changes in the microbiome with reductions in short-chain fatty acid (SCFA)-producing bacteria and increases in endotoxin-producing bacteria likely contribute to the pathogenesis of PD. GPR109A, a G-protein coupled receptor found on the surface of the intestinal epithelium and immune cells, plays a key role in controlling intestinal permeability and the inflammatory cascade. The absence of GPR109A receptors is associated with decreased concentration of tight junction proteins, leading to increased intestinal permeability and susceptibility to inflammation. In inflammatory states, butyrate acts via GPR109A to increase concentrations of tight junction proteins and improve intestinal permeability. Niacin deficiency is exacerbated in PD by dopaminergic medications. Niacin supplementation has been shown to shift macrophage polarization from pro-inflammatory to an anti-inflammatory profile. Niacin and butyrate, promising nutrients and unique ligands for the G protein-coupled receptor GPR109A, are reviewed in this paper in detail. Full article

(This article belongs to the Special Issue Gut Microbiota in Cognition, Behaviour and Alzheimer's Disease)

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25 pages, 3256 KiB

Open AccessReview

The Gut Microbiome, Aging, and Longevity: A Systematic Review

by Varsha D. Badal, Eleonora D. Vaccariello, Emily R. Murray, Kasey E. Yu, Rob Knight, Dilip V. Jeste and Tanya T. Nguyen

Nutrients 2020, 12(12), 3759; https://0-doi-org.brum.beds.ac.uk/10.3390/nu12123759 - 07 Dec 2020

Cited by 187 | Viewed by 19003

Abstract

Aging is determined by complex interactions among genetic and environmental factors. Increasing evidence suggests that the gut microbiome lies at the core of many age-associated changes, including immune system dysregulation and susceptibility to diseases. The gut microbiota undergoes extensive changes across the lifespan, and age-related processes may influence the gut microbiota and its related metabolic alterations. The aim of this systematic review was to summarize the current literature on aging-associated alterations in diversity, composition, and functional features of the gut microbiota. We identified 27 empirical human studies of normal and successful aging suitable for inclusion. Alpha diversity of microbial taxa, functional pathways, and metabolites was higher in older adults, particularly among the oldest-old adults, compared to younger individuals. Beta diversity distances significantly differed across various developmental stages and were different even between oldest-old and younger-old adults. Differences in taxonomic composition and functional potential varied across studies, but Akkermansia was most consistently reported to be relatively more abundant with aging, whereas Faecalibacterium, Bacteroidaceae, and Lachnospiraceae were relatively reduced. Older adults have reduced pathways related to carbohydrate metabolism and amino acid synthesis; however, oldest-old adults exhibited functional differences that distinguished their microbiota from that of young-old adults, such as greater potential for short-chain fatty acid production and increased butyrate derivatives. Although a definitive interpretation is limited by the cross-sectional design of published reports, we integrated findings of microbial composition and downstream functional pathways and metabolites, offering possible explanations regarding age-related processes. Full article

(This article belongs to the Special Issue Gut Microbiota in Cognition, Behaviour and Alzheimer's Disease)

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