Alzheimer’s disease and gut microbiota modifications: The long way between preclinical studies and clinical evidence

Mancuso, Cesare; Santangelo, Rosaria

doi:10.1016/j.phrs.2017.12.009

Cited by 164 publications

(98 citation statements)

References 92 publications

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“…A better understanding of the role of gut microbiota in the pathogenesis of AD and the close association between gut dysbiosis, increased intestinal permeability, and neurological dysfunction creates opportunity for potential therapeutic interventions. 108 The results of numerous studies confirm the beneficial effect of probiotics by enhancing intestinal epithelial integrity, protecting against barrier disruption, reducing proinflammatory response, and inhibiting initiation or propagation of neuroinflammation and neurodegeneration. 3,109 For example, it has been shown in vitro that Enterococcus faecium and Lactobacillus rhamnosus reduce TNF-α production and supplementation of these probiotic strains in animal studies reduced oxidative stress markers and induced antioxidant enzymes in the brain.…”

Section: Microbiota Modulation As a Therapeutic Target In Alzheimer'smentioning

confidence: 87%

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Brain-Gut-Microbiota Axis in Alzheimer’s Disease

Kowalski

Mulak

2019

J Neurogastroenterol Motil

520

389

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Disturbances along the brain-gut-microbiota axis may significantly contribute to the pathogenesis of neurodegenerative disorders. Alzheimer’s disease (AD) is the most frequent cause of dementia characterized by a progressive decline in cognitive function associated with the formation of amyloid beta (Aβ) plaques and neurofibrillary tangles. Alterations in the gut microbiota composition induce increased permeability of the gut barrier and immune activation leading to systemic inflammation, which in turn may impair the blood-brain barrier and promote neuroinflammation, neural injury, and ultimately neurodegeneration. Recently, Aβ has also been recognized as an antimicrobial peptide participating in the innate immune response. However, in the dysregulated state, Aβ may reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry may elicit cross-seeding of misfolding and induce microglial priming. The Aβ seeding and propagation may occur at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing or via other cells as astrocytes, fibroblasts, microglia, and immune system cells. A growing body of experimental and clinical data confirms a key role of gut dysbiosis and gut microbiota-host interactions in neurodegeneration. The convergence of gut-derived inflammatory response together with aging and poor diet in the elderly contribute to the pathogenesis of AD. Modification of the gut microbiota composition by food-based therapy or by probiotic supplementation may create new preventive and therapeutic options in AD.

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Section: Microbiota Modulation As a Therapeutic Target In Alzheimer'smentioning

confidence: 87%

“…sectional human studies. 48,108 Some limitations in translating basic research results to humans are related to the host-specific interactions with microbiota. To enhance and forward AD research largescale epidemiological studies investigating the complex interactions between genes, microbiota, diet, and aging should be conducted.…”

Section: Discussionmentioning

confidence: 99%

Brain-Gut-Microbiota Axis in Alzheimer’s Disease

Kowalski

Mulak

2019

J Neurogastroenterol Motil

520

389

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“…Once generated, the latter hypothetically triggers a systemic inflammatory response which compromises complex brain functions, such as learning and memory. Clinical studies have shown that, in cognitively impaired elderly patients with brain amyloidosis, there is lower abundance in the gut of E. rectale and B. fragilis, two bacterial species which have an anti-inflammatory activity, versus a greater amount of pro-inflammatory genera such as Escherichia/Shigella [49].…”

Section: Alzheimer Disease (Ad)mentioning

confidence: 99%

Antibiotic-modified Microbiome Might Be Responsible for Non-contagious World-wide Epidemics

Ternák¹

2019

BIO

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The rapid, pandemic-like, spread of certain noncontagious diseases (NCDs), like (childhood) obesity, type2 diabetes mellitus, particularly in children, autism, Alzheimer diseases, etc. prompted the researches to try to find appropriate explanation for this phenomenon. The well-known association between antibiotic enriched fodder and the weight gain of food animals, through the modification of the gut flora, clearly raises the possibility of similar relationship in human beings as well, which was described in several publications. The role of obesity in the development of diabetes is a well-known also. The antibiotic consumption pattern in the World clearly demonstrated the extensive utilization of the broad spectrum antibiotics, starting about three decades ago, and the appearance of still active degradation products in the environment, which might reenter into humans and animals again, and as the result of the alteration of human microbiome, could induce the pandemiclike NCDs. The yet to be explained rapid increase of prevalence of autism and Alzheimer diseases observed in the past three decades is alarming. According to a CDC survey, the prevalence of autism in the surveyed population was estimated as 16.8 per 1,000 (one in 59) children aged 8 years, which is considered as a 150% increase from the year 2000. The prevalence of Alzheimer's disease in Europe was estimated at 5.05% (95% CI, 4.73-5.39). Microbiome alterations were observed in both cases and obesity is present in the 30% of autism as well. Putting together the mosaics from relevant publications, it might be concluded that we face the long term side effects of antibiotic consumption/pollution manifesting, through the alteration of microbioms as the pandemic appearance of certain NCDs. The restoration of the "normal" gut flora by fecal microbiota transfer (FMT) might be an option to influence those conditions.

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“…The need to create functional foods is caused by a significant deterioration in the health status of the population, which is largely due to the decline in food quality and safety [1,2]. Nowadays, there are new facts on the connection of intestinal microbiome with diseases of not only of gastrointestinal tract, but also with obesity, diabetes, malignant tumors, allergic, autoimmune, cardiovascular diseases and other [3][4][5][6][7]. Currently, everyday products are added with a large number of various physiologically unjustified food additives that lead to "diseases of civilization" and to a violation in the composition of the normal microflora of the gastrointestinal tract.…”

mentioning

confidence: 99%

Development of Functional Beverages on the Base of Whey

САУБЕНОВА¹,

ОЛЕЙНИКОВА²

2018

OF THE NATIONAL ACADEMY OF SCIENCES OF THE REPUBLIC OF KAZAKHS

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Г л а в н ы й р е д а к т о р академик НАН РК, д.м.н., проф. Ж. А. Арзыкулов Абжанов Архат проф. (Бостон, США), Абелев С.К. проф. (Москва, Россия), Айтхожина Н.А. проф., академик (Казахстан) Акшулаков С.К. проф., академик (Казахстан) Алчинбаев М.К. проф., академик (Казахстан) Батпенов Н.Д. проф. член-корр.НАН РК (Казахстан) Березин В.Э., проф., чл.-корр. (Казахстан) Берсимбаев Р.И., проф., академик (Казахстан) Беркинбаев С.Ф. проф. (Казахстан) Бисенбаев А.К. проф., академик (Казахстан) Бишимбаева Н.К. проф., академик (Казахстан) Ботабекова Т.К. проф., чл.-корр. (Казахстан) Джансугурова Л. Б. к.б.н., проф. (Казахстан) Ellenbogen Adrian prof. (Tel-Aviv, Israel), ЖамбакинК.Ж. проф., академик (Казахстан), зам. гл. ред. Заядан Б.К. проф., чл.-корр. (Казахстан) Ishchenko Alexander, prof. (Villejuif, France) Исаева Р.Б. проф. (Казахстан) Кайдарова Д.Р. проф., академик (Казахстан) Кохметова А.М. проф., чл.-корр. (Казахстан) Кузденбаева Р.С. проф., академик (Казахстан) Локшин В.Н., проф., чл.-корр. (Казахстан) Лось Д.А. prof. (Москва, Россия) Lunenfeld Bruno prof. (Израиль) Макашев Е.К. проф., чл.-корр. (Казахстан) Миталипов Ш.М. (Америка) Муминов Т.А. проф., академик (Казахстан) Огарь Н.П. проф., чл.-корр. (Казахстан) Омаров Р.Т.к.б.н., проф. (Казахстан) Продеус А.П. проф. (Россия) Purton Saul prof. (London, UK) Рахыпбеков Т.К. проф., чл.-корр. (Казахстан) Сапарбаев Мурат проф. (Париж, Франция) Сарбасов Дос проф. (Хьюстон, США) Турысбеков Е. К., к.б.н., асс.проф. (Казахстан) Шарманов А.Т. проф. (США) «Известия НАН РК. Серия биологическая и медицинская».

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Alzheimer’s disease and gut microbiota modifications: The long way between preclinical studies and clinical evidence

Cited by 164 publications

References 92 publications

Brain-Gut-Microbiota Axis in Alzheimer’s Disease

Brain-Gut-Microbiota Axis in Alzheimer’s Disease

Antibiotic-modified Microbiome Might Be Responsible for Non-contagious World-wide Epidemics

Development of Functional Beverages on the Base of Whey

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