Probiotic Supplementation in Patients with Alzheimer’s Dementia - An Explorative Intervention Study

Leblhuber, Friedrich; Steiner, Kostja; Schuetz, Burkhard; Fuchs, Dietmar; Gostner, Johanna M.

doi:10.2174/1389200219666180813144834

Cited by 207 publications

(163 citation statements)

References 51 publications

(60 reference statements)

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“…[43] Another study in dementia showed a decrease in previously elevated zonulin levels after probiotic treatment as a possible hint towards an improvement. [37] Although we did not find any differences in stool zonulin and calprotectin levels, we found an increase in DAO levels which has been proven to be a valuable serum biomarker of gut barrier dysfunction. [44][45][46][47] Also, Ginko biloba, a commonly used phytotherapeutic drug in dementia, was able to reduce DAO levels in an animal model of alcoholic liver disease, indicating both the validity of DAO as a permeability biomarker and that gut permeability may be a modifiable and relevant therapeutic target.…”

Section: Discussioncontrasting

confidence: 59%

“…[3] , [2] Recently an exploratory pilot study showed that probiotic modulation of the gut microbiome in dementia can lead to increased abundance of butyrate producing bacterial strains. [37] We also found that Clostridium clostridioforme and the genus Eisenbergiella increased with increasing cognitive impairment. Clostridium clostridioforme has mainly been described as a human pathogen [38] but has also been described to be associated with vegetarian diet.…”

Section: Discussionmentioning

confidence: 53%

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Dysbiosis in dementia is associated with gut barrier dysfunction and linked to malnutrition and prescription drug use

Stadlbauer

Engertsberger

Komarova

et al. 2019

Preprint

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Background: Dementia is an increasing public health threat worldwide. The pathogenesis of dementia has not been fully elucidated yet. Inflammatory processes are hypothesized to play an important role as a driver for cognitive decline but the origin of inflammation is not clear. We hypothesize that disturbances in gut microbiome composition, gut barrier dysfunction, bacterial translocation and resulting inflammation are associated with cognitive dysfunction in dementia. Methods: To test this hypothesis, a cohort of 23 patients with dementia and 18 age and sex matched controls without cognitive impairments were studied. Gut microbiome composition, gut barrier dysfunction, bacterial translocation and inflammation were assessed from stool and serum samples. Malnutrition was assessed by Mini Nutritional Assessment Short Form (MNA-SF), detailed information on drug use was collected. Microbiome composition was assessed by 16s sequencing, QIIME 2 and Calypso 7.14 tools. Results: Dementia was associated with dysbiosis characterized by differences in beta diversity and changes in taxonomic composition. Gut permeability was increased as evidenced by increased serum diamine oxidase levels and systemic inflammation was confirmed by increased soluble cluster of differentiation 14 levels (sCD14). BMI and statin use use had the strongest impact on microbiome composition.Conclusion: Dementia is associated with changes in gut microbiome composition and increased biomarkers of gut permeability and inflammation. Lachnospiraceae NK4A136 group as a potentially butyrate producing bacterial strain was reduced in dementia. Malnutrition and drug intake were factors, that impact on microbiome composition and function. Increasing butyrate producing bacteria and targeting malnutrition may be promising therapeutic targets in dementia.Trial Registration: NCT03167983

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Section: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 53%

Dysbiosis in dementia is associated with gut barrier dysfunction and linked to malnutrition and prescription drug use

Stadlbauer

Engertsberger

Komarova

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…Probiotic supplementation with Lactobacillus plantarum in combination with SSRI treatment improved cognitive performance and decreased Kyn concentrations in patients with major depression [compared to SSRI treatment alone, (266)]. Supplementation with a multispecies probiotic had a beneficial effect on Trp metabolism in trained athletes (267) and influenced Trp degradation and gut bacteria composition in patients with Alzheimer's disease (268). Additionally, highly adaptive lactobacilli where shown to produce the AhR ligand indole-3-aldehyde, which enabled IL-22 transcription for the fine tuning of host mucosal reactivity (269).…”

Section: Nutrition Microbiome and Physical Activity And Its Associamentioning

confidence: 99%

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

et al. 2020

Self Cite

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Many patients with cancer suffer from anemia, depression, and an impaired quality of life (QoL). These patients often also show decreased plasma tryptophan levels and increased kynurenine concentrations in parallel with elevated concentrations of Th1 type immune activation marker neopterin. In the course of anti-tumor immune response, the pro-inflammatory cytokine interferon gamma (IFN-γ) induces both, the enzyme indoleamine 2,3-dioxygenase (IDO) to degrade tryptophan and the enzyme GTP-cyclohydrolase I to form neopterin. High neopterin concentrations as well as an increased kynurenine to tryptophan ratio (Kyn/Trp) in the blood of cancer patients are predictive for a worse outcome. Inflammation-mediated tryptophan catabolism along the kynurenine pathway is related to fatigue and anemia as well as to depression and a decreased QoL in patients with solid tumors. In fact, enhanced tryptophan breakdown might greatly contribute to the development of anemia, fatigue, and depression in cancer patients. IDO activation and stimulation of the kynurenine pathway exert immune regulatory mechanisms, which may impair anti-tumor immune responses. In addition, tumor cells can degrade tryptophan to weaken immune responses directed against them. High IDO expression in the tumor tissue is associated with a poor prognosis of patients. The efficiency of IDO-inhibitors to inhibit cancer progression is currently tested in combination with established chemotherapies and with immune checkpoint inhibitors. Inflammation-mediated tryptophan catabolism and its possible influence on the development and persistence of anemia, fatigue, and depression in cancer patients are discussed.

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“…Similar results were obtained from investigations using genetic AD mouse models with Bifidobacterium breve strain A1 [95], SLAB51 (probiotic formulation, [96]) but also with Lactobacillus acidophilus, Lactobacillus fermentum, Bifidobacterium lactis, and Bifidobacterium longum in rodent sporadic AD models due to amyloid-β injection [97][98][99]. As only one explorative intervention study reports on a small cohort of AD human patients [100], the usefulness in humans is still not proven. Additionally, the underlying mechanism has not been resolved.…”

Section: Therapeutic Strategies Derived From Microbes Against Human Amentioning

confidence: 57%

Amyloidogenic Peptides in Human Neuro-Degenerative Diseases and in Microorganisms: A Sorrow Shared Is a Sorrow Halved?

Endres

2020

Molecules

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The term “amyloid” refers to proteinaceous deposits of peptides that might be generated from larger precursor proteins e.g., by proteolysis. Common to these peptides is a stable cross-β dominated secondary structure which allows self-assembly, leading to insoluble oligomers and lastly to fibrils. These highly ordered protein aggregates have been, for a long time, mainly associated with human neurodegenerative diseases such as Alzheimer’s disease (Amyloid-β peptides). However, they also exert physiological functions such as in release of deposited hormones in human beings. In the light of the rediscovery of our microbial commensals as important companions in health and disease, the fact that microbes also possess amyloidogenic peptides is intriguing. Transmission of amyloids by iatrogenic means or by consumption of contaminated meat from diseased animals is a well-known fact. What if also our microbial commensals might drive human amyloidosis or suffer from our aggregated amyloids? Moreover, as the microbial amyloids are evolutionarily older, we might learn from these organisms how to cope with the sword of Damocles forged of endogenous, potentially toxic peptides. This review summarizes knowledge about the interplay between human amyloids involved in neurodegenerative diseases and microbial amyloids.

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Probiotic Supplementation in Patients with Alzheimer’s Dementia - An Explorative Intervention Study

Cited by 207 publications

References 51 publications

Dysbiosis in dementia is associated with gut barrier dysfunction and linked to malnutrition and prescription drug use

Dysbiosis in dementia is associated with gut barrier dysfunction and linked to malnutrition and prescription drug use

Inflammation-Induced Tryptophan Breakdown is Related With Anemia, Fatigue, and Depression in Cancer

Amyloidogenic Peptides in Human Neuro-Degenerative Diseases and in Microorganisms: A Sorrow Shared Is a Sorrow Halved?

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