Cited by 951Probiotics and Fermented FoodsDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index; none of the 44 sources its claims cite is checked for support yet.

Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial

Open access

Akbari, Elmira, Asemi, Zatollah, Daneshvar Kakhaki, Reza, Bahmani, Fereshteh, Kouchaki, Ebrahim, Tamtaji, Omid Reza, Hamidi, Gholam Ali, Salami, Mahmoud·2016·Frontiers in Aging Neuroscience

DOI 10.3389/fnagi.2016.00256PMC PMC5105117

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Abstract

Alzheimer's disease (AD) is associated with severe cognitive impairments as well as some metabolic defects. Scant studies in animal models indicate a link between probiotics and cognitive function. This randomized, double-blind and controlled clinical trial was conducted among 60 AD patients to assess the effects of probiotic supplementation on cognitive function and metabolic status. The patients were randomly divided into two groups (n=30 in each group) treating with either milk (control group) or a mixture of probiotic (probiotic group). The probiotic supplemented group took 200 ml/day probiotic milk containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum and Lactobacillus fermentum (2×109 CFU/g for each) for 12 weeks. Mini-mental state examination (MMSE) score was recorded in all subjects before and after the treatment. Pre- and post-treatment fasting blood samples were obtained to determine the related markers. After 12 weeks intervention, compared with the control group (-5.03%±3.00), the probiotic treated (+27.90%±8.07) patients showed a significant improvement in the MMSE score (P<0.001). In addition, changes in plasma malondialdehyde (-22.01%±4.84 vs. +2.67%±3.86 µmol/L, P<0.001), serum high-sensitivity C-reactive protein (-17.61%±3.70 vs. +45.26%±3.50 µg/mL, P<0.001), homeostasis model of assessment-estimated insulin resistance (+28.84%±13.34 vs.+76.95%±24.60, P=0.002), Beta cell function (+3.45%±10.91 vs. +75.62%±23.18, P=0.001), serum triglycerides (-20.29%±4.49 vs. -0.16%±5.24 mg/dL, P=0.003) and quantitative insulin sensitivity check index (-1.83±1.26 vs. -4.66±1.70, P=0.006) in the probiotic group were significantly varied compared to the control group. We found that the probiotic treatment had no considerable effect on other biomarkers of oxidative stress and inflammation, fasting plasma glucose and other lipid profiles. Overall, the current study demonstrated that probiotic consumption for 12 weeks positively affects cognitive function and some metabolic statuses in the AD patients.

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Written from the paper’s full text.

TL;DR

In a 12-week randomized, double-blind controlled trial of 60 Alzheimer’s disease patients, probiotic milk supplementation improved MMSE scores and some metabolic/inflammatory markers compared with control milk. The authors conclude probiotics may have favorable effects on cognition and selected metabolic statuses in AD, but not on all oxidative stress, inflammation, glucose, or lipid measures.

Key findings

MMSE score improved in the probiotic group (+27.90% ± 8.07) versus worsening in the control group (−5.03% ± 3.00; P < 0.001).
Probiotic treatment significantly changed plasma MDA (−22.01% ± 4.84 vs. +2.67% ± 3.86 μmol/L, P < 0.001), serum hs-CRP (−17.61% ± 3.70 vs. +45.26% ± 3.50 μg/mL, P < 0.001), HOMA-IR (+28.84% ± 13.34 vs. +76.95% ± 24.60, P = 0.002), HOMA-B (+3.45% ± 10.91 vs. +75.62% ± 23.18, P = 0.001), serum triglycerides (−20.29% ± 4.49 vs. −0.16% ± 5.24 mg/dL, P = 0.003), and QUICKI (−1.83 ± 1.26 vs. −4.66 ± 1.70, P = 0.006).
No considerable effect was found on other oxidative stress and inflammation biomarkers, fasting plasma glucose, or other lipid profiles (LDL, HDL, total cholesterol).
No side effects were reported following probiotic administration.

Methods

Randomized, double-blind, controlled 12-week clinical trial in 60 AD patients aged 60–95 years residing at welfare organizations in Kashan and Esfahan, Iran; participants were randomized to control milk (n = 30) or probiotic milk (n = 30), matched at baseline for disease severity based on gender, BMI, and age.
Probiotic group received 200 ml/day milk containing Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum (2 × 10^9 CFU/g for each) for 12 weeks; control group received milk.
Primary outcome was MMSE; secondary outcomes included oxidative stress, inflammation, and metabolic biomarkers from fasting blood samples at weeks 0 and 12. Analyses used intention-to-treat with LOCF for missing values, independent t-tests, and ANCOVA adjustment for baseline biochemical values, age, and BMI.

Limitations

The paper states that measuring fecal bacteria loads before and after probiotic supplementation in AD patients was very difficult.
The paper states that cognition was assessed only with the MMSE, and that other cognitive criteria and additional inflammatory/oxidative biomarkers such as IL-6, TNF-α, catalase, and SOD would be informative.
Evident from the text: the sample was small (60 randomized; 52 completed), with deaths/dropouts during the study, and baseline serum triglycerides, VLDL, and HDL differed significantly between groups, although the authors report adjustment did not considerably change findings.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3389/fnagi.2016.00256

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 44 cited sources checked · 0 supported · 0 flagged

A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Findings of the current study indicated that while the probiotic supplementation decreased the plasma MDA and the serum hs-CRP levels it was ineffective on other biomarkers of oxidative stress and inflammation.”
- Also stated in: § Discussion · boosted
  “Overall, the current study demonstrated that 12 weeks consumption of probiotic in the AD patients had favorable effects on MDA, hs-CRP, markers of insulin metabolism, and serum levels of triglyceride and VLDL.”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
Load-bearingStrength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Findings of the current study indicated that while the probiotic supplementation decreased the plasma MDA and the serum hs-CRP levels it was ineffective on other biomarkers of oxidative stress and inflammation.”
- Also stated in: § Discussion · plain
  “However, the pobiotic treatment was inefective on other biomarkers of oxidative stress and inflammation, FPG, and other lipid profiles.”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes

Show all 27 claims

It may state two separate claims as one. 23
Probably not a substantial claim. 35

In the paper
“The MMSE was used to assess cognition in the AD subjects (Folstein et al., 1975).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Materials and methods > Assessment of outcomes
What the sources say
- Not checked yetcites Folstein et al., 1975 source
Load-bearingStrength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
Probably not a substantial claim.
In the paper
“In our previous work, we have shown that probiotics efficiently reverse the impaired spatial learning and memory as well as synaptic transmission in diabetes mellitus (Davari et al., 2013).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Davari et al., 2013 source
Strength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It is demonstrated that other brain related disorders such as multiple sclerosis (Kouchaki et al., 2016) and stress are also influenced by probiotics (Liang et al., 2015).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Kouchaki et al., 2016 source
- Not checked yetcites Liang et al., 2015 source
Strength:boosted· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Increased biomarkers of oxidative stress (Furman et al., 2016), inflammation and chronic neuroinflammation are reported to be associated with many neurodegenerative disorders of central nervous system (CNS) including AD (Leszek et al., 2016).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Background
What the sources say
- Not checked yetcites Furman et al., 2016 source
- Not checked yetcites Leszek et al., 2016 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Gareau reported that intestinal dysbiosis in germ free animals (containing no microbiota), bacterial infection with an enteric pathogen and administration of probiotics can modulate cognitive behaviors including learning and memory (Gareau, 2014).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Background
What the sources say
- Not checked yetcites Gareau, 2014 source
Load-bearingStrength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“AD patients are predisposed to some complications including increased oxidative stress (Sultana et al., 2011), morbidity, mortality (Schelke et al., 2016), microvascular disease, dyslipidemia, and insulin resistance (Sridhar et al., 2015).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Sultana et al., 2011 source
- Not checked yetcites Schelke et al., 2016 source
- Not checked yetcites Sridhar et al., 2015 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Missing values were treated based on Last-Observation-Carried-Forward method (LOCF) (Lachin, 2016).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Materials and methods > Statistical methods
What the sources say
- Not checked yetcites Lachin, 2016 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Probiotics intake may improve markers of insulin metabolism and lipid profiles by reducing cytokines and suppressing the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway (Shi et al., 2006) and gut microbiota-short chain fatty acids (SCFA)-hormone axis (Yadav et al., 2013).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Shi et al., 2006 source
- Not checked yetcites Yadav et al., 2013 source
Load-bearingStrength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Consumption of symbiotic bread containing the heat-resistant probiotic Lactobacillus sporogenes (1 × 108 CFU/g) for 8 weeks also decreased the serum triglyceride and VLDL concentrations in patients with type 2 diabetes (Shakeri et al., 2014).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Shakeri et al., 2014 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Accordingly, high lipid levels could be one of the risk factors for AD (Reitz et al., 2010).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Reitz et al., 2010 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Oxidative stress is a frequently observed feature of AD, although its pathological significance is not understood (Selvarajah et al., 2011).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Selvarajah et al., 2011 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Evidence indicates that, through production of reactive oxygen species, oxidative stress acts as vehicle for deposition and accumulation of amyloid β (Aβ) in AD (Kim et al., 2015).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Kim et al., 2015 source
Strength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For example, it was reported that 6 weeks probiotic treatment caused no significant change in inflammatory factors of diabetic patients (Mazloom et al., 2013).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Mazloom et al., 2013
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Dysfunctions in GABA-signaling are linked to anxiety and depression, defects in synaptogenesis and cognitive impairments (Aziz et al., 2013; Mitew et al., 2013).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Aziz et al., 2013 source
- Not checked yetcites Mitew et al., 2013 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
It may state two separate claims as one.
In the paper
“Also the glutamatergic NMDA receptors are involved in the most important excitatory neurotransmission of brain (Talaei et al., 2016) which is engaged in the neural circuits involved in learning and memory.”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Talaei et al., 2016 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Furthermore, 8 weeks consumption of capsules containing 108 CFU/g of L. casei by the people suffered from rheumatoid arthritis displayed no significant within- and between-group changes in MDA and TAC levels (Vaghef-Mehrabany et al., 2015).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Vaghef-Mehrabany et al., 2015 source
Strength:plain· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In addition, Zarrati et al. (2014) showed that 8 weeks consumption of yogurt, enriched by L. acidophilus, Bifidobacterium langum, and L. casei (108 CFU/g each) decreased inflammatory cytokines in overweight people.”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Zarrati et al., 2014 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Some evidence from clinical studies support the fact that abnormal cholesterol metabolism in the brain leads to progressive cognitive dysfunction (Wang et al., 2014).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Wang et al., 2014 source
Strength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Further, findings from germ free animals indicated a decreased level of brain derived neurotrophic factor (BDNF), important neurotrophic factor in the neuronal growth and survival, and a reduced expression of some subunits of N-Methyl-D-aspartate (NMDA) receptors (Sudo et al., 2004) involved in most abundant neurotransmission in brain (Salami et al., 2000).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Sudo et al., 2004 source
- Not checked yetcites Salami et al., 2000 source
Load-bearingStrength:hedged· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
It may state two separate claims as one.
In the paper
“Emerging evidence has demonstrated that brain insulin resistance, as a key mediator in prediabetes and diabetes mellitus, may take a role in AD (Cervellati et al., 2016).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Cervellati et al., 2016 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“It has also been postulated that oxidative stress may decrease the activity of α-secretase, which promotes the expression and activity of β and γ-secretase, leading to the increased production of Aβ (Tan et al., 2013).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Tan et al., 2013 source
Strength:hedged· not yet calibratedCausal:conditional· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Insulin resistance plays an important role in the development of cognitive impairment in primary elderly hypertensive patients (Ma et al., 2015).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Ma et al., 2015
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Consistently, in a meta-analysis study, Kasińska and Drzewoski (2015) reported a reduced HOMA-IR and insignificant FGP in probiotic treated subjects.”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Kasińska and Drzewoski, 2015
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Consistent to our findings, a significant reduction in MDA levels was reported in type 2 diabetic patients after consuming probiotic yogurt (Ejtahed et al., 2012).”
§ Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial > Discussion
What the sources say
- Not checked yetcites Ejtahed et al., 2012 source
Strength:plain· not yet calibratedCausal:direct· not yet calibrated
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passes
Probably not a substantial claim. The paper’s conclusions may not depend on it.

50 of 50

The paper relies on this without support.
No direct study has considered gut microbiota manipulation in Alzheimer's disease patients.
“However, no direct study has considered the gut microbiota manipulation in AD patients.”
The paper relies on this without support.
Studies considering the effect of probiotic supplements on brain behavioral phenomena are scant.
“Studies considering the effect of probiotic supplements on brain behavioral phenomena are scant.”
The paper relies on this without support.
This study is the first to evaluate the beneficial effects of probiotic supplementation on cognitive function, biomarkers of oxidative stress, inflammation, and metabolic status in patients with Alzheimer's disease.
“To the best of our knowledge, this study is the first evaluating the beneficial effects of probiotic supplementation on cognitive function, biomarkers of oxidative stress, inflammation and metabolic status in patients with AD.”
The paper relies on this without support.
The probiotic intervention changed the gut microbiota in the AD patients.
“Measurement of fecal bacteria loads before and after the probiotic supplementation in the AD patients was very difficult.”

4 of 4

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2 retracted

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Kouchaki, E., Tamtaji, O. R., Salami, M., Bahmani, F., Daneshvar Kakhaki, R., Akbari, E., Tajabadi-Ebrahimi, M., Jafari, P., & Asemi, Z. (2017) · Clinical Nutrition · doi:10.1016/j.clnu.2016.08.015 · Cited by 317 · cited 1×
“It is demonstrated that other brain related disorders such as multiple sclerosis (Kouchaki et al., 2016) and stress are also influenced by probiotics (Liang et al., 2015).”
BackgroundSelf-citation
Retracted
RETRACTED ARTICLE: The effects of probiotics on mental health and hypothalamic–pituitary–adrenal axis: A randomized, double-blind, placebo-controlled trial in petrochemical workers
Mohammadi, A. A., Jazayeri, S., Khosravi‐Darani, K., Solati, Z., Mohammadpour, N., Asemi, Z., Adab, Z., Djalali, M., Tehrani‐Doost, M., Hosseini, M., et al. (2015) · Nutritional Neuroscience · doi:10.1179/1476830515y.0000000023 · Cited by 241
Self-citation
Retracted
“Mini-mental state”
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · cited 2×
“It is generally agreed that probiotic strains should be of host origin with a beneficial effect on the host, withstand into food stuff with a high count, withstand transits through intestine and colonize lumen of the tract, produce antimicrobial agents, and technologically appropriate for…”
BackgroundMethod
Clinical diagnosis of Alzheimer's disease: Report of the NINCDS‐ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915
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“Plasma total antioxidant capacity (TAC) was measured using the ferric reducing antioxidant power method developed by Benzie and Strain (1996).”
Method
[Japanese version of the Neuropsychiatric Inventory--a scoring system for neuropsychiatric disturbance in dementia patients].
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,012
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Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Cryan, J. F., & Dinan, T. G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3346 · Cited by 4,572 · cited 2×
“The difference between the two groups of testing was statistically significant (P < 0.001).”
BackgroundInfluential

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Shewale, 2014, Selection criteria for probiotics: a review, Int. J. Probiotics Prebiotics, 9, 17

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“acidophilus, had neuroprotective effects on aging-related cognitive dysfunctions in clinical and preclinical studies (Akbari et al., 2016; Athari Nik Azm et al., 2018; Tamtaji et al., 2019; Yang et al., 2020).”
Background
Therapeutic Implications of Probiotics in the Gut Microbe-Modulated Neuroinflammation and Progression of Alzheimer’s Disease
Murai, T., & Matsuda, S. (2023) · Life · doi:10.3390/life13071466 · Cited by 20
Probiotics Improve Cognitive Impairment by Decreasing Bacteria-Related Pattern Recognition Receptor-Mediated Inflammation in the Gut-Brain Axis of Mice
Yang, X., Zhao, Y., Xue, L., Wang, H., Zeng, J., Du, J., & Xu, Z. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2204092 · Cited by 19
Evaluation of improvement of cognitive impairment in older adults with probiotic supplementation: A systematic review and meta-analysis
Kou, J., Kang, H., Hu, L., Wang, D., Wang, S., Wang, Q., & Yang, Z. (2023) · Geriatric Nursing · doi:10.1016/j.gerinurse.2023.09.009 · Cited by 21
Improvement of Key Molecular Events Linked to Alzheimer’s Disease Pathology Using Postbiotics
Bulacios, G. A., Cataldo, P. G., Naja, J. R., Chaves, E., Taranto, M. P., Minahk, C. J., Hebert, E. M., & Saavedra, L. (2023) · ACS Omega · doi:10.1021/acsomega.3c06805 · Cited by 20
Probiotics in plant-based food matrices: A review of their health benefits
Nascimento, S. S. D. C., Passos, T. S., & Júnior, F. C. D. S. (2024) · PharmaNutrition · doi:10.1016/j.phanu.2024.100390 · Cited by 19
In vitro neuroprotective activities of two distinct probiotic consortia
Michael, D. R., Davies, T. S., Loxley, K. E., Allen, M. D., Good, M. A., Hughes, T. R., & Plummer, S. F. (2019) · Beneficial Microbes · doi:10.3920/bm2018.0105 · Cited by 21
Precision Nutrition and Gut–Brain Axis Modulation in the Prevention of Neurodegenerative Diseases
Tuigunov, D. N., Sinyavskiy, Y. A., Nurgozhin, T. S., Zholdassova, Z., Smagul, G., Omarov, Y., Dolmatova, O., Yeshmanova, A., & Omarova, I. (2025) · Nutrients · doi:10.3390/nu17193068 · Cited by 24
“…Lactobacillus and Bifidobacterium strains, in cognitive assessment, a decrease in the levels of proinflammatory cytokines, markers of oxidative damage (malondialdehyde, 8-hydroxy-2 ′ -deoxyguanosine), as well as an improvement in metabolic parameters in patients with Alzheimer’s disease [88–90].”
Probiotics-targeting new milestones from gut health to mental health
Dey, G., & Mookherjee, S. (2021) · FEMS Microbiology Letters · doi:10.1093/femsle/fnab096 · Cited by 18
Evaluating the Role of Probiotics in the Prevention and Management of Age-Related Diseases
Kiousi, D. E., Kouroutzidou, A. Z., Neanidis, K., Matthaios, D., Pappa, A., & Galanis, Α. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073628 · Cited by 19
When the microbiome helps the brain‐current evidence
Drljača, J., Milosevic, N. P., Milanović, M., Abenavoli, L., & Milić, N. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14076 · Cited by 19
2- O - β - D -Glucopyranosyl- L -ascorbic acid, an ascorbic acid derivative isolated from the fruits of Lycium barbarum L., ameliorates high fructose-induced neuroinfl ammation in mice: involvement of gut microbiota and leaky gut
Dong, W., Peng, Y., Chen, G., Xie, Z., Xu, W., Zhou, W., Mi, J., Lu, L., Sun, Y., Zeng, X., et al. (2023) · Food Science and Human Wellness · doi:10.26599/fshw.2022.9250020 · Cited by 18
A review of the auditory-gut-brain axis
Graham, A. S., Ben‐Azu, B., Tremblay, M., Torre, P., Senekal, M., Laughton, B., van der Kouwe, A. J. W., Jankiewicz, M., Kaba, M., & Holmes, M. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1183694 · Cited by 22
“, 2018) and neurological (Akbari et al., 2016; Dutta et al., 2019) disorders in patients.”
Background
A Review on the Protective Effects of Probiotics against Alzheimer’s Disease
Mishra, V., Yadav, D., Solanki, K. S., Koul, B., & Song, M. (2023) · Biology · doi:10.3390/biology13010008 · Cited by 20
“Mental state assessments revealed that probiotics had a favorable impact on cognitive functioning [166].”
Background
Probiotics for Preventing Cognitive Impairment in Alzheimer’s Disease
Wong, C. B., Kobayashi, Y., & Xiao, J. (2018) · IntechOpen eBooks · doi:10.5772/intechopen.79088 · Cited by 19
“The probiotic treatment also has favorable effects on the levels of malondialdehyde (MDA) and high-sensitivity C-reactive protein (hs-CRP), improved insulin resistance, pancreatic beta cell secretion, and metabolic status with respect to controls; albeit the changes in other biomarkers of oxidative stress and inflamma…”
Background
Administration of pre/probiotics with conventional drug treatment in Alzheimer’s disease
Angelucci, F., Hort, J., & Vališ, M. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.266057 · Cited by 18
“In addition, it has been demonstrated that a diet rich in probiotics not only affect normal brain activity but also induces significant cognitive improvements in AD patients (Akbari et al., 2016).”
The Microbiota-gut-immune-glia (MGIG) Axis in Major DepressionPreprint
Rudzki, L., & Maes, M. H. J. (2020) · Preprints.org · doi:10.20944/preprints202002.0084.v1 · Cited by 18
Prevention and Treatment of Alzheimer's Disease Via the Regulation of the Gut Microbiota With Traditional Chinese Medicine
Long, J., Zhang, J., Zeng, X., Wang, M., & Wang, N. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70101 · Cited by 18
Effect of nutritional supports on malnutrition, cognition, function and biomarkers of Alzheimer’s disease: a systematic review
Kocatürk, R. R., Temizyürek, A., Özcan, Ö. Ö., Erguzel, T. T., Karahan, M., Konuk, M., & Tarhan, N. (2022) · International Journal of Neuroscience · doi:10.1080/00207454.2022.2079506 · Cited by 17
“When the studies are examined, there are twelve studies incorporating blood lipid parameters [27,41,43,53– 57, 59,64 , 66].”
BackgroundResultInfluential
Ingestion of Lacticaseibacillus rhamnosus Fmb14 prevents depression-like behavior and brain neural activity via the microbiota–gut–brain axis in colitis mice
Zhao, H., Chen, X., Zhang, L., Tang, C., Meng, F., Zhou, L., Ping, Z., Lu, Z., & Lu, Y. (2023) · Food & Function · doi:10.1039/d2fo04014j · Cited by 19
Exploring the effect of gut microbiome on Alzheimer's disease
Pourahmad, R., Saleki, K., Zare, M., Aram, C., Farsani, A. S., Banazadeh, M., & Tafakhori, A. (2024) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2024.101776 · Cited by 20
“As reported previously, supplementation with Lac-tobacilli and Bifidobacteria-based probiotics also enhanced Mini-Mental State Examination (MMSE) scores in AD patients in a clinical investigation [86].”
Result
Young at Gut—Turning Back the Clock with the Gut Microbiome
Narasimhan, H., Ren, C. C., Deshpande, S., & Sylvia, K. E. (2021) · Microorganisms · doi:10.3390/microorganisms9030555 · Cited by 17
Application of psychobiotics in clinical treatment of mental disorders: Neurodevelopmental disorders, neurodegenerative diseases, depression and anxiety
Cui, J., Wang, W., Tang, Y., Feng, S., Liu, H., & Hao, Z. (2025) · Interdisciplinary medicine · doi:10.1002/inmd.20240041 · Cited by 21
Flavanones as Modulators of Gut Microbiota and Cognitive Function
Cichoń, N., Szelenberger, R., Stela, M., Podogrocki, M., Gorniak, L., & Bijak, M. (2025) · Molecules · doi:10.3390/molecules30102203 · Cited by 20
“In a randomized controlled trial (RCT), Akbari et al. [86] demonstrated that a 12-week supplementation with a probiotic mixture containing Lactobacillus acidophilus , Lactobacillus casei , Bifidobacterium bifidum , and Lactobacillus fermentum improved Mini-Mental State Examination (MMSE) scores in…”
Intermittent supplementation with Akkermansia muciniphila and galactooligosaccharides modulates Alzheimer’s disease progression, gut microbiota, and colon short-chain fatty acid profiles in mice
Kunevičius, A., Vijaya, A. K., Atzeni, A., Mingaila, J., Šimoliūnė, I., Jamontas, R., Kezeviciute, E., Gueimonde, M., Meškys, R., Baltriukienė, D., et al. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1617980 · Cited by 17
Simvastatin improves learning and memory impairment via gut-brain axis regulation in an ovariectomized/D-galactose Alzheimer's rat model
Zahedi, E., Sanaeierad, A., Nikbakhtzadeh, M., Roghani, M., & Zamani, E. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114611 · Cited by 16
The effect of probiotics on select cognitive domains in mild cognitive impairment and Alzheimer's disease: A systematic review and meta-analysis
Tripathi, S., Kaushik, M., Dwivedi, R., Tiwari, P., Tripathi, M., & Dada, R. (2024) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823241289039 · Cited by 16
Unraveling the Gut‐Brain‐Immune Interplay in Herpes Simplex Virus‐Associated Neurodegeneration
Bautista, J., Ávila‐Coello, D., Hidalgo‐Tinoco, C., Bueno‐Miño, J., & López‐Cortés, A. (2025) · Journal of Medical Virology · doi:10.1002/jmv.70504 · Cited by 16
The endocannabinoid system: a bridge between alzheimer’s disease and gut microbiota
Bisogno, T., Lauritano, A., & Piscitelli, F. (2021) · Life · doi:10.3390/life11090934 · Cited by 16
Gut Microbiota and Alzheimer’s Disease: Pathophysiology and Therapeutic Perspectives
Li, Y., Wang, R., Li, Q., Wang, Y., & Guo, J. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210381 · Cited by 16
Mapping trends and hotspot regarding gastrointestinal microbiome and neuroscience: A bibliometric analysis of global research (2002–2022)
Yang, J., Deng, Y., Cai, Y., Liu, Y., Peng, L., Luo, Z., & Li, D. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1048565 · Cited by 16
“Probiotic supplementation (Lactobacillus acidophilus, Lactobacillus bifidobacterium, and Lactobacillus fermentans) improves cognitive function and metabolic status in patients with Alzheimer’s disease (Akbari et al., 2016).”
BackgroundMethod
The Influence of the Gut Microbiota on Alzheimer's Disease: A Narrative Review
Yin, J.-T., Xu, X., Jin, C.-Y., Yuan, X., & Wang, X. (2023) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2202038 · Cited by 15
“improved cognitive function in AD patients treated with probiotics [174].”
Background
Microbiome Alterations and Alzheimer’s Disease: Modeling Strategies with Transgenic Mice
López-Villodres, J. A., Escamilla, A., Mercado-Sáenz, S., Alba-Tercedor, C., Rodríguez‐Pérez, L., Arranz‐Salas, I., Sanchez-Varo, R. M., & Bermúdez, D. (2023) · Biomedicines · doi:10.3390/biomedicines11071846 · Cited by 16
Probiotic therapy modulates the brain-gut-liver microbiota axis in a mouse model of traumatic brain injury
Amaral, W. Z., Kokroko, N., Treangen, T. J., Villapol, S., & Gómez‐Pinilla, F. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167483 · Cited by 15
The role of the gut microbiota in neurodegenerative diseases targeting metabolism
Fu, Y., Gu, Z., Cao, H., Zuo, C., Huang, Y., Song, Y., Jiang, Y., & Wang, F. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1432659 · Cited by 17
Mental Disorders Linked to Crosstalk between The Gut Microbiome and The Brain
Choi, T.-Y., Choi, Y. P., & Koo, J. W. (2020) · Experimental Neurobiology · doi:10.5607/en20047 · Cited by 18
“We previously confirmed that symptoms of various mental disorders were improved by several kinds of bacteria or their combinations [12, 13, 31-34, 70-72].”
Background
A State-of-Art Review of the Vicious Circle of Sleep Disorders, Diabetes and Neurodegeneration Involving Metabolism and Microbiota Alterations
Versace, S., Pellitteri, G., Sperotto, R., Tartaglia, S., Porto, A. D., Catena, C., Gigli, G. L., Cavarape, A., & Valente, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310615 · Cited by 17
Gut Microbiota: An Ally in the Mechanisms and Interventions of Healthy Aging
Chatterjee, S. S., Hebbani, A. V., & Syed, K. (2025) · Gastrointestinal Disorders · doi:10.3390/gidisord7040068 · Cited by 16
Bifidobacterium promotes retinal ganglion cell survival by regulating the balance of retinal glial cells
Zhao, X., Xu, M., Zhao, Z., Wang, Y., Liu, Y., Zhang, T., Wan, X., Jiang, M., Luo, X., Shen, Y., et al. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14165 · Cited by 14
Gut microbiota in perioperative neurocognitive disorders: current evidence and future directions
Sun, Y., Wang, K., & Zhao, W. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1178691 · Cited by 15
Nutritional strategies modulating the gut microbiome as a preventative and therapeutic approach in normal and pathological age-related cognitive decline: a systematic review of preclinical and clinical findings
Sproten, R., Nöhr, D., & Guseva, D. (2024) · Nutritional Neuroscience · doi:10.1080/1028415x.2023.2296727 · Cited by 15
Advances of therapy for Alzheimer's disease: An updated review
Mei, C., Zhan, J., Zhu, S., Zhang, Y., Xiong, C., Wang, J., Xu, Y. J., Zhong, H., & Cheng, J. (2024) · Brain‐X · doi:10.1002/brx2.68 · Cited by 15
Exerkine irisin mitigates cognitive impairment by suppressing gut-brain axis-mediated inflammation
Zhang, H., Liang, J., Huang, J., Wang, M., Wu, L., Wu, T., & Chen, N. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.10.031 · Cited by 16
“Biﬁdobacterium exhibits anti-aging effects on promoting cognitive capacity and metabolic level of AD mice [78,79], which is possibly correlated with neuron regeneration [28].”
Lactobacillus plantarum and Bifidobacterium longum Alleviate High-Fat Diet-Induced Obesity and Depression/Cognitive Impairment-like Behavior in Mice by Upregulating AMPK Activation and Downregulating Adipogenesis and Gut Dysbiosis
Yun, S.-W., Shin, Y.-J., Ma, X., & Kim, D. (2024) · Nutrients · doi:10.3390/nu16223810 · Cited by 14
Mechanism of Action and Beneficial Effects of Probiotics in Amateur and Professional Athletes
Nami, Y., Barghi, A., Shahgolzari, M., Salehian, M., & Haghshenas, B. (2024) · Food Science & Nutrition · doi:10.1002/fsn3.4658 · Cited by 15
“Further research is needed to determine specific probiotic strains, doses, and supplementation durations for consistent and significant effects (Akbari et al. 2016).”
Gene-environment interactions determine risk for dementia: the influence of lifestyle on genetic risk for dementia
Patten, K. T., & Lein, P. J. (2019) · Annals of Translational Medicine · doi:10.21037/atm.2019.09.155 · Cited by 15
“Indeed, recent clinical trials of prebiotic or probiotic supplementation to change the microbiome have shown promising results in AD or MCI patients, even with short-term treatment (12-15).”
Background
Neuroprotective Effects of Probiotic-Supplemented Diet on Cognitive Behavior of 3xTg-AD Mice
Tan, C., Liu, Y., Zhang, H., Di, C., Xu, D., Liang, C., Zhang, N., Han, B., & Lang, W. (2022) · Journal of Healthcare Engineering · doi:10.1155/2022/4602428 · Cited by 14
Retracted
Can probiotics mitigate age-related neuroinflammation leading to improved cognitive outcomes?
Anderson, R. C. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.1012076 · Cited by 15
The Oral–Brain Axis in Alzheimer’s Disease: From Microbial Dysbiosis to Neurodegeneration
Felicetti, A., Azzolino, D., Piro, P. P., Lopes, G. C. D., Rezaeinezhad, N., Lovero, R., Bocchio‐Chiavetto, L., Colella, M., & Passarelli, P. C. (2025) · Microorganisms · doi:10.3390/microorganisms13122741 · Cited by 14
“Probiotic supplementation has shown modest improvements in cognition and inflammatory/metabolic profiles in patients with mild cognitive impairment or AD [156,157,164].”
Exploring the Role of Lipid-Binding Proteins and Oxidative Stress in Neurodegenerative Disorders: A Focus on the Neuroprotective Effects of Nutraceutical Supplementation and Physical Exercise
Scarfò, G., Piccarducci, R., Daniele, S., Franzoni, F., & Martini, C. (2022) · Antioxidants · doi:10.3390/antiox11112116 · Cited by 16
Nutritional intervention for diabetes mellitus with Alzheimer's disease
Li, Z., Li, S., Xiao, Y., Zhong, T., Yu, X., & Wang, L. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.1046726 · Cited by 12
Milmed Yeast Alters the LPS-Induced M1 Microglia Cells to Form M2 Anti-Inflammatory Phenotype
Armeli, F., Mengoni, B., Maggi, E., Mazzoni, C., Preziosi, A., Mancini, P., Businaro, R., Lenz, T., & Archer, T. (2022) · Biomedicines · doi:10.3390/biomedicines10123116 · Cited by 14
The effects of the interplay between vitamins, antibiotics, and gut microbiota on the pathogenesis and progression of dementia: A systematic review and meta‐analysis
Prajjwal, P., Inban, P., Sai, V. P., Karnati, S. S., Lam, J. R., John, J., Sulaimanov, M., Tekuru, Y., Haq, M. W. U., Marsool, M. D. M., et al. (2024) · Health Science Reports · doi:10.1002/hsr2.1808 · Cited by 13
Protective Effects of Bifidobacterium Breve MCC1274 as a Novel Therapy for Alzheimer’s Disease
Abdelhamid, M., Counts, S., Zhou, C., Hida, H., Kim, J., Michikawa, M., & Jung, C. (2025) · Nutrients · doi:10.3390/nu17030558 · Cited by 16
IUPHAR review: From gut to brain: The role of gut dysbiosis, bacterial amyloids, and metabolic disease in Alzheimer’s disease
Inan, S., Wilson, R. P., & Tükel, Ç. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107693 · Cited by 15
A red lentils-based synbiotic cookie exerts neuroprotective effects in a mouse model of Alzheimer's disease
Bonfili, L., Grasselli, F. M., Cuccioloni, M., Cecarini, V., Lufrano, D., Vittadini, E., Galosi, L., Sonsini, G., Ubaldi, M., Turck, J. L., et al. (2025) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2025.109904 · Cited by 16
The microbial guardians: Unveiling the role of gut microbiota in shaping neurodegenerative disease
Izzeddine, N. A., Ahmad, K., Bacha, C., Jabbour, M., Najjar, M., Salhab, S., Ghadieh, H. E., Kanaan, A., Azar, S. T., Khattar, Z. A., et al. (2025) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2025.05.014 · Cited by 19
“…a 12-week regimen of probiotic milk, containing Bifidobacterium bifidum , Lactobacillus acidophilus , Lactobacillus casei , and Lactobacillus fermentum at a daily dose of 200 mL (2 × 10 9 CFU/g each), resulted in enhanced cognitive function and improved metabolic status (Akbari et al., 2016).”
Probiotics: The Next Dietary Strategy against Brain Aging
Ong, J.-S., Lew, L.-C., Hor, Y.-Y., & Liong, M. (2022) · Preventive Nutrition and Food Science · doi:10.3746/pnf.2022.27.1.1 · Cited by 13
The role of the gut microbiota in the pathophysiology of mental and neurological disorders
Pusceddu, M. M., & Bas-Prior, J. M. D. (2020) · Psychiatric Genetics · doi:10.1097/ypg.0000000000000255 · Cited by 15
“After 12 weeks of intervention, AD-treated patients showed cognitive improvements compared to AD controls (Akbari et al., 2016) (Table 3).”
MethodResult
A Novel Probiotic Formula, BIOCG, Protects Against Alzheimer’s-Related Cognitive Deficits via Regulation of Dendritic Spine Dynamics
Sun, M., Bao, W., Huang, C., Xia, Z., Zhang, C., Wang, G., Wang, R., Li, J., Roux, S., Li, Q., et al. (2021) · Current Alzheimer Research · doi:10.2174/1567205018666211022091110 · Cited by 13
Probiotic Bifico Ameliorates Depression- and Anxiety-Like Behaviors Induced by Estrogen Deficiency via NLRP3 Inflammasome Inhibition
Yu, X., Yu, X., Yang, Y., Cheng, W., Shi, M., Chen, L., Zhang, X., & Xu, Y. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s511931 · Cited by 13
“66 Our study also found that probiotics could improve the BBB permeability by increasing the expression of tight-junction proteins Occludin and ZO-1 in the hippocampus of OVX rats.”
Efficacy and Safety of Lactobacillus delbrueckii subsp. lactis CKDB001 Supplementation on Cognitive Function in Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Baek, H.-I., Kwon, S.-Y., Noh, H.-J., Son, S. Y., Joo, J. C., & Park, S. J. (2025) · Nutrients · doi:10.3390/nu17203313 · Cited by 15
“These results align with multiple clinical trials indicating that probiotic supplementation may enhance cognitive performance in individuals with MCI or early Alzheimer’s disease, particularly impacting memory and overall cognition [6,38].”
The Serotonergic System and Amyotrophic Lateral Sclerosis: A Review of Current Evidence
Lu, Y., Cheng, Y., Zhu, Y., Cui, L., & Li, X. (2023) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-023-01320-0 · Cited by 12
“The effects of interventions, such as faecal microbiota transplantation or probiotic administration, in some neurological disorders, such as AD (Akbari et al. 2016), PD (Tamtaji et al.”
Background
Fasting, a Potential Intervention in Alzheimer's Disease
Zeng, Z., Zhang, H., Wang, X., Shen, J., & Chen, D. (2024) · Journal of Integrative Neuroscience · doi:10.31083/j.jin2303050 · Cited by 12
“…Lactobacillus casei, Bifidobacterium , and Lactobacillus fermentum to older adults with AD for 12 weeks was found to elevate plasma malondialdehyde and high-sensitivity C-reactive protein levels while enhancing β -cell function, reducing insulin resistance, and improving cognitive performance [68].”
Alzheimer's disease approaches - Focusing on pathology, biomarkers and clinical trial candidates
Hroudová, J., & Fišar, Z. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111069 · Cited by 13
Dietary Strategies to Mitigate Alzheimer’s Disease: Insights into Antioxidant Vitamin Intake and Supplementation with Microbiota–Gut–Brain Axis Cross-Talk
Ngah, W. Z. W., Ahmad, H. F., Ankasha, S. J., Makpol, S., & Tooyama, I. (2024) · Antioxidants · doi:10.3390/antiox13121504 · Cited by 12
The Role of Probiotics in Modulating the Gut Microbiome in Alzheimer’s Disease: A Review
Dong, Y., Wu, X., Zhang, Y., Hu, A., Zhou, Q., Yue, X., Liu, Z., & Li, M. (2025) · Foods · doi:10.3390/foods14091531 · Cited by 15
“In a randomized double-blind placebo-controlled trial by Akbari et al. [177], patients with AD were treated with probiotics for 12 weeks.”
Efficacy of probiotics in patients with cognitive impairment: A systematic review and meta-analysis
Ma, M., Li, B., Qu, Z., Liu, S., & Li, S. (2025) · PLoS ONE · doi:10.1371/journal.pone.0321567 · Cited by 13
“Among the ten papers included in the analysis, five were classified as quality A(26, 27, 34–36), with an equal number, five, designated as quality B(25, 28, 31–33).”
Angiotensin (1–7) Expressing Probiotic as a Potential Treatment for Dementia
Hernandez, A. R., Banerjee, A., Carter, C. S., & Buford, T. W. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.629164 · Cited by 12
“For example, probiotic administration for 12 weeks was reported to improve Mini-Mental State Examination (MMSE) scores as well as several markers of metabolic health including insulin sensitivity in AD patients relative to the placebo group (30 participants/group) (Akbari et al., 2016).”
Can Control Infections Slow Down the Progression of Alzheimer’s Disease? Talking About the Role of Infections in Alzheimer’s Disease
Shi, M., Li, C., Tian, X., Chu, F., & Zhu, J. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.685863 · Cited by 13
Probiotics Treatment Can Improve Cognition in Patients with Mild Cognitive Impairment: A Systematic Review
Sánchez-de-Lara-Sánchez, S., & Sánchez‐Pérez, A. M. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220615 · Cited by 13
Bifidobacterium animalis subsp. lactis and arginine mixture intake improves cognitive flexibility in mice
Ikuta, K., Joho, D., Kakeyama, M., & Matsumoto, M. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1164809 · Cited by 13
Oral Galactose Provides a Different Approach to Incretin-Based Therapy of Alzheimer's Disease
Šalković‐Petrišić, M. (2018) · Journal of Neurology and Neuromedicine · doi:10.29245/2572.942x/2018/4.1204 · Cited by 12
Does probiotic supplementation aid weight loss? A randomized, single-blind, placebo-controlled study with Bifidobacterium lactis BS01 and Lactobacillus acidophilus LA02 supplementation
Czajeczny, D., Kabzińska, K., & Wójciak, R. W. (2020) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-020-00983-8 · Cited by 12
Salivary Aβ Secretion and Altered Oral Microbiome in Mouse Models of AD
Floden, A. M., Sohrabi, M., Nookala, S., Cao, J., & Combs, C. K. (2021) · Current Alzheimer Research · doi:10.2174/1567205018666210119151952 · Cited by 13
Cognitive impairment and CSF proteome modification after oral bacteriotherapy in HIV patients
Landi, C., Santinelli, L., Bianchi, L., Shaba, E., Ceccarelli, G., Cavallari, E. N., Borrazzo, C., Pinacchio, C., Scagnolari, C., Vullo, V., et al. (2019) · Journal of NeuroVirology · doi:10.1007/s13365-019-00801-7 · Cited by 12
Clostridioides difficile and neurological disorders: new perspectives
Biazzo, M., Allegra, M., & Deidda, G. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.946601 · Cited by 11
“In clinical trials in people with Alzheimer’s disease, a mixed-species probiotic (including Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus fermentum) improved the mini-mental state examination (MMSE) scores (Akbari et al., 2016).”
Background
Systemic Metabolism and Mitochondria in the Mechanism of Alzheimer’s Disease: Finding Potential Therapeutic Targets
Song, M., & Fan, X. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098398 · Cited by 11
Mapping Research Trends and Hotspots in the Link between Alzheimer’s Disease and Gut Microbes over the Past Decade: A Bibliometric Analysis
Xiu, R., Sun, Q., Li, B., & Wang, Y. (2023) · Nutrients · doi:10.3390/nu15143203 · Cited by 12
The Role of Probiotics In Tissue Engineering And Regenerative Medicine
Golchin, A., Ranjbarvan, P., Parviz, S., Shokati, A., Naderi, R., Rasmi, Y., Kiani, S., Moradi, F., Heidari, F., Saltanatpour, Z., et al. (2023) · Regenerative Medicine · doi:10.2217/rme-2022-0209 · Cited by 12
Nourishing Immunity and Combatting Neuroinflammation: The Power of Immunonutrition and The Microbiome
Dübüş, E. N., Lamminpää, I., Nannini, G., & Niccolai, E. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2808178 · Cited by 12
“The study found that probiotic consumption for 12 weeks positively affects cognitive function, improving the metabolic status and decreasing inflammation [59].”
Background
Potential Therapeutic Effects of Bifidobacterium breve MCC1274 on Alzheimer’s Disease Pathologies in AppNL-G-F Mice
Abdelhamid, M., Jung, C., Zhou, C., Inoue, R., Chen, Y., Sento, Y., Hida, H., & Michikawa, M. (2024) · Nutrients · doi:10.3390/nu16040538 · Cited by 13
“Overall, the findings of the present study and previous observations suggest that B . breve MCC1274 administration has anti-AD effects and can be used as a treatment for AD.”
Result
Zeolite and Neurodegenerative Diseases
Panaiotov, S., Tancheva, L. P., Kalfin, R. E., & Petkova-Kirova, P. S. (2024) · Molecules · doi:10.3390/molecules29112614 · Cited by 15
Probiotic Lactobacilli Ameliorate Antibiotic-Induced Cognitive and Behavioral Impairments in Mice
Рашидовна, Я. Д., Novoselova, V., Alexandrova, A., Arslanova, A., Yakovleva, O. V., Shaidullov, I. F., Nikolaev, Y. A., El-Registan, G. I., Кудрин, В. С., & Ситдикова, Г. Ф. (2024) · Microbiology Research · doi:10.3390/microbiolres15030099 · Cited by 11
Neurodegenerative Disorders and the Gut-Microbiome-Brain Axis: A Literature Review
Dandamudi, B. J., Dimaano, K. A. M., Shah, N., AlQassab, O., Al-Sulaitti, Z., Nelakuditi, B., & Mohammed, L. (2024) · Cureus · doi:10.7759/cureus.72427 · Cited by 17
Thinking outside the brain: Gut microbiome influence on innate immunity within neurodegenerative disease
Merchak, A. R., Bolen, M. L., Tansey, M. G., & Menees, K. B. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00476 · Cited by 12
Effects of Probiotics on Neurodegenerative Disease-Related Symptoms and Systemic Inflammation: A Systematic Review
Zhu, F., Yin, S., Wang, Y., Zhong, Y., Ji, Q., & Wu, J. (2024) · International Journal of General Medicine · doi:10.2147/ijgm.s499406 · Cited by 11
Rewiring Mood: Precision Psychobiotics as Adjunct or Stand-Alone Therapy in Depression Using Insights from 19 Randomized Controlled Trials in Adults
Menni, A.-E., Theodorou, H., Tzikos, G., Theodorou, I. M., Semertzidou, E., Stelmach, V., Shrewsbury, A. D., Stavrou, G., & Kotzampassi, K. E. (2025) · Nutrients · doi:10.3390/nu17122022 · Cited by 13
Therapeutic potential of traditional chinese medicine polysaccharides in alzheimer's disease via modulation of gut microbiota: A review
Wang, T., Gao, C., Dong, X., & Li, L. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.146160 · Cited by 12
The Influence of Nutrition in Alzheimer's Disease: Neuroinflammation and the Microbiome vs. Transmissible Prion
Bello-Corral, L., Sánchez-Valdeón, L., Verdejo, I. C., Seco‐Calvo, J., Fernández-Fernández, J. A., & Fernández, N. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.677777 · Cited by 12
Efficiency of probiotics in elderly patients undergoing orthopedic surgery for postoperative cognitive dysfunction: a study protocol for a multicenter, randomized controlled trial
Zhang, X., Chen, Y., Tang, Y., Zhang, Y., Zhang, X. L., & Su, D. (2023) · Trials · doi:10.1186/s13063-023-07167-6 · Cited by 13
Increased Circulating ADMA in Young Male Rats Caused Cognitive Deficits and Increased Intestinal and Hippocampal NLRP3 Inflammasome Expression and Microbiota Composition Alterations: Effects of Resveratrol
Hsu, M., Huang, Y., Chen, Y., Sheen, J., & Huang, L. (2023) · Pharmaceuticals · doi:10.3390/ph16060825 · Cited by 11
Effects of Bifidobacterium Lactis BS01 and Lactobacillus Acidophilus LA02 on cognitive functioning in healthy women
Czajeczny, D., Kabzińska, K., & Wójciak, R. W. (2021) · Applied Neuropsychology Adult · doi:10.1080/23279095.2021.1967155 · Cited by 11
“Positive effects from trials on clinical populations and animal models seem to support this hypothesis (Akbari et al., 2016; Bajaj, 2017; Bruce-Keller et al., 2015; Leblhuber et al., 2018; Luo et al., 2014; Rudzki et al., 2019; Steenbergen et al., 2015).”
Background
Efficacy of probiotic supplementation in influencing cognitive function in Alzheimer's disease: A systematic review and meta‐analysis
Liu, W., Guo, J., Dong, Y., Li, J., & Wang, Y. (2025) · Journal of Food Science · doi:10.1111/1750-3841.70037 · Cited by 12
Probiotics as a Complementary Medicine in Neurologic Disorders
Jafari, M., Alipour, M., Zamani, S., Amiri, A. M., Pourabbas, P., & Bibalan, M. H. (2025) · Health Science Reports · doi:10.1002/hsr2.71422 · Cited by 12
Lactobacillus plantarum LP104 improved intestinal and brain inflammation by modulating TLR4 pathway and gut flora in alcohol liver injury mice
Zhang, Y., Ma, Y., Fan, Y., Gao, Y., He, Y., Wang, Y., Nan, B., Liu, J., Liu, J., & Wang, Y. (2024) · Food Bioscience · doi:10.1016/j.fbio.2024.105424 · Cited by 10
Cancer-Related Cognitive Impairment and the Potential of Dietary Interventions for the Prevention and Mitigation of Neurodegeneration
Crowder, S. L., Gudenkauf, L. M., Hoogland, A. I., Han, H. S., Small, B. J., Carson, T. L., Parker, N. H., Booth‐Jones, M., & Jim, H. (2024) · Cancer Research · doi:10.1158/0008-5472.can-24-3041 · Cited by 11
Evaluating the Efficacy of Secondary Metabolites in Antibiotic-Induced Dysbiosis: A Narrative Review of Preclinical Studies
Andrei, C., Zanfirescu, A., Ormeneanu, V.-P., & Negreș, S. (2025) · Antibiotics · doi:10.3390/antibiotics14020138 · Cited by 11
Potential benefits of kefir and its compounds on Alzheimer's disease: A systematic review
Tanure, Y. C. B., Mafra, A. C. M., Guimarães, B. L. M., Magalhães, R. C., Fagúndez, C., do Nascimento, I. J. B., & Brito, J. C. M. (2025) · Brain Behavior and Immunity Integrative · doi:10.1016/j.bbii.2025.100115 · Cited by 12
Effect of the probiotic Escherichia coli Nissle 1917 on serum levels of NADPH oxidase-2 and lipopolysaccharide in patients with Alzheimer's disease
Loffredo, L., Alfano, A. R., Ettorre, E., Desideri, G., Carnevale, R., Forte, M., Maglione, V., Bartimoccia, S., Castellani, V., Totè, C. M., et al. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251345157 · Cited by 12

Authors: Akbari, E., Asemi, Z., Daneshvar Kakhaki, R., Bahmani, F., Kouchaki, E., Tamtaji, O. R., Hamidi, G. A., & Salami, M.
Affiliations: Kashan University of Medical Sciences (IR)
Corresponding author: Asemi, Zatollah
Salami, Mahmoud
ORCID: Asemi, Zatollah
Bahmani, Fereshteh
Kouchaki, Ebrahim
Tamtaji, Omid Reza
Hamidi, Gholam Ali
Salami, Mahmoud
Venue: Frontiers in Aging Neuroscience
Publisher: Frontiers Media SA
Published: 2016-11-10
Volume: 8
Pages: 256-256
ISSN: 1663-4365 (ISSN-L)
DOI: 10.3389/fnagi.2016.00256
PMC: PMC5105117
OpenAlex: W2549210709
Semantic Scholar: 7a1f1dc8208ef2c3d7013ce699ff50704195c24d
Cited by: 946
References: 60
Citations by year: 2026: 75 · 2025: 111 · 2024: 120 · 2023: 136 · 2022: 139 · 2021: 119 · 2020: 94 · 2019: 87 · 2018: 44 · 2017: 19
FWCI: 63.01
Type: journal article
Language: en
Update notices: expression_of_concern (2020-10-07)
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Aging Neuroscience (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Kashan University of Medical Sciences
Topics: Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: Alzheimer's disease, probiotics, probiotic milk, cognitive function, metabolic status, Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium bifidum, Lactobacillus fermentum, malondialdehyde, oxidative stress, C-reactive protein, insulin resistance, beta-cell function, triglycerides, Mini-Mental State Examination

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Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer's Disease: A Randomized, Double-Blind and Controlled Trial

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