ISSN: 0973-7510
E-ISSN: 2581-690X
and Pinaki DeyAlzheimer’s disease is neurodegenerative dementia which has significant health complications in the old age group. An imbalance in gut microbiota can influence to cause several diseases like chronic disorders, depression, type II diabetics, and neurological disorders like AD. Aging is one of the major causes of the development of neurodegenerative disease due to the decreasing levels of neurotransmitters, oxidative stress, chronic inflammation, and apoptosis. These harmful effects of aging can be prevented by probiotics usage. The gut-microbiota is capable to control the brain function through the gut-brain axis. Lactobacillus strains are considered as beneficial microorganism because of its importance of the maintenance in healthy intestinal microflora, immunomodulation, and intestinal pathogenic intervention. They have diverse applications in the medical field with properties like antioxidant, anticancer, anti-inflammatory, anti-proliferative, anti-obesity, and anti-diabetic activities. Probiotic supplementation with Lactobacillus strains shows an optimistic trend to use it as a significant therapy for cognitive symptoms. This review article put forwards the significance of the gut-brain axis and the contribution of Lactobacillus strains as a probiotic supplement and its therapeutic innovations for future aspects and the limitation to treat AD-related pathogenesis are briefly elucidated.
Alzheimer’s disease, neurodegenerative disease, Lactobacillus strains, dementia, gastrointestinal tract, gut-microbiota, gut-brain axis
Alzheimer’s disease (AD) is a highly prevalent neurodegenerative disease in the aged group of people and nearly 44 million of the world population have AD associated dementia and estimated to be raised as 4 million in India and 5.3 million in the United States respectively1. It is a progressive, neurodegenerative ailment, a beginning of neurological decline, and stands to be an extreme and inevitably a life-threatening disease unless the death is intervened by another cause2. AD mostly affects the parts of the brain related with higher mental capacities, explicitly the neocortex and hippocampus3.
The etiology of AD is not completely perceived due to the multifactorial mechanisms underlying the disease. There are many factors which have been linked to the development and progression of AD which includes aging, cholinergic deficit, extracellular deposition of amyloid-β protein, formed from amyloid precursor protein (APP), intracellular deposition of hyperphosphorylated tau as neurofibrillary tangles4, oxidative stress, loss of neuronal synapses and pyramidal neurons5,6. Among these factors, the cholinergic deficit, extracellular deposition of amyloid-β protein, intracellular deposition of tau as neurofibrillary tangles, and oxidative stress are considered to play a significant part in AD pathogenesis7.
In cholinergic deficit, the damage of cholinergic neurons happens due to the decrease of neurotransmitter like acetylcholine8, an important neurotransmitter involved in critical physiological processing of the brain will get hydrolysed by the acetylcholinesterase in the synaptic cleft, an essential reaction to allow the cholinergic neurons into its resting state. The level of acetylcholine can be maintained by using an acetylcholinesterase inhibitor is used as the treatment for AD7.
The extracellular accumulation of amyloid-β protein is formed by the β pathway due to the hydrolysis of amyloid precursor protein (APP) by β-secretase (BACE1) and then by γ-secretase results in the development of insoluble Aβ plagues7. Aβ plagues are the potential target for AD due to its pathological feature of severe neuronal loss. The treatment strategy to reduce the Aβ production is by targeting on β- and γ-secretase but causes serious side effects like blindness and large catalytic pocket7,9.
The tau is a microtubule-binding protein that helps in stabilizing and providing flexibility to the microtubules10. In pathological condition, the tau will get disintegrated from the microtubules and forms tau aggregations causing intracellular deposition of neurofibrillary tangles causes impairment in neuronal axons and therefore causes neurodegeneration7. Due to the incomplete understanding of AD, the tau-targeted treatment stays challenging7. oxidative stress is another significant factor of AD pathogenesis brought about by the imbalance between Reactive Oxygen species (ROS) production and antioxidants levels making harm to the cells by excessive production of ROS11.
Based on different strategies, different drugs are used for the treatment of AD. which includes Aβ plagues inhibitors (Tramiprosate and ALZ-801), anti-tau (EpoD), anti-inflammatory (NSAID) and cholinergic enhancement drug (Donepezil, Galantamine, Rivastigmine, and Tacrine) which inhibits the acetylcholinesterase (AChE)12,13 but these drugs can cause serious side effects like nausea, vomiting, muscle cramps, increased bowel movement frequencies, loss of appetite, dizziness, confusion, constipation14.
Various studies showed that the loss of biodiversity in the gastrointestinal tract of humans can lead to AD. The gut microbiota can maintain the homeostasis of the brain by producing neurotransmitters, nerve signals, and metabolites transmitted along the gut-brain axis15. Human lifestyle changes contributed a depletion in gut microbiota which could lead to a high risk of AD pathogenesis15. So, an alteration in gut microbiota through a probiotic supplementation with beneficial microorganisms could reduce the risk of AD pathogenesis and also side effects associated with the AD drugs.
The Gut microbiota and the Gut-Brain Axis
The gut microbiota consists of numerous bacterial species dwelling inside the gastrointestinal tract (GIT) existing as symbionts with the human host16 and is believed to play an essential role in physiology17,18. A 51% of gut microbiota are belonging to the Firmicutes phyla comprising the groups of Clostridium coccoides and Clostridium leptum and the most acknowledged Lactobacillus genera and 48% consists of the Bacteroidetes phyla comprising well recognized genera of Prevotella and Bacteroides19,20. The remaining 1% of microbiota is the less-known phyla, comprising Proteobacteria, Actinobacteria, Bifidobacteria, Fusobacteria, Spirochaetes, Verrucomicrobia, and Lentispaerae19,21.
The gut microbiota got recognition due to its connectedness to the body parts remarkably the brain. The GIT is connected with the Central nervous system (CNS) through a signaling pathway of networks including the autonomic, immune systems, neuroendocrine, bacterial metabolites, and neuromodulatory molecules are collectively called as the “gut-brain axis”19,22,23. The regulatory factors are mainly common in between enteric nervous system (ENS) and CNS19,24.
The microbiota and intestinal enterochromaffin (EC) cells secreted hormones and metabolites cross with several biochemical pathways influencing the CNS processing creating a way to communicate between the external environment in link with the gut microbiota and brain19. The enteric nervous system formed by millions of nerves end in the GIT mucosa, helps to control the functions of the intestine and communicates with the brain through the nerve vagus and is responsible for the transmission of signals from the brain to GIT through the autonomic nervous system23. Studies suggest that an imbalance in the gut microbiota can influence the progression of neurological disorder and can initiate disease onset and also collapses the permeability of the intestine which leads to inflammatory conditions in both gut and brain, because of the proinflammatory cytokines which can enter into the bloodstream and reach the brain19,25,26. Evidence suggests that the importance of inflammation should not be underrated, since it plays a critical role in various chronic disorders, like type II diabetes27, AD28, and depression23,29.
The genus lactobacillus
The lactobacilli are Gram-positive, rods or coccobacilli non-spore formers, strict fermentative, aero-tolerant, or anaerobic with complex nutritional requirements like carbohydrates, amino acids, peptides, fatty acid esters, salts, nucleic acid derivatives, and vitamins30. Lactobacilli are either homofermentative (yielding lactic acid more than 85%) or heterofermentative (yielding lactic acid, carbon dioxide, and ethanol/acetic acid) depends upon a carbon source as glucose30. The strains of Lactobacillus are referred to as safe consumption bacteria because of their efficiency in gut defense mechanisms31. Lactobacillus is a genuine member of lactic acid bacteria (LAB) and other genera includes Streptococcus, Pediococcus, Lactococcus, Leuconostoc, Bifidobacterium, Carnobacterium, Enterococcus and Sporolactobacillus32.
A probiotic is a supplementary diet consist of beneficial living microorganisms which is found as normal flora with little or no pathogenicity33,34. These probiotics are believed to have an effect on preventing or treating diseases like gastrointestinal sickness, diarrhoea, irritatable bowel syndrome, and inflammatory bowel disease (IBD)35, and also possess anticancer, antioxidant, anti-obesity, antidiabetic, and antihyperlipidemic activities1. Using of Lactobacilli as a probiotic strain have a long history of safe use because of its normal inhabit in human and animal GIT36 and also considered as a beneficial microorganism because of its roles in immunomodulation, enteric pathogenic intervention, and healthy intestinal microflora maintenance37. Due to the attractiveness of “all-natural” products to treat diseases, Lactobacillus sp. (Table 1) supplemented products received popularity35.
Table (1):
Description of Lactobacillus sp. used as probiotics.
Species name |
Morphological characteristics |
Growth requirements |
Strains isolated from |
Reference |
|---|---|---|---|---|
Lactobacillus acidophilus |
Acid-loving bacteria. rods cells with rounded ends, 0.6-0.9 by 1.5-6 µm, seen as single, in pairs, and in short chains |
Obligatory homofermentative Requires riboflavin, pantothenic acid (vitamin B5), folic acid, and niacin for growth |
Isolated from the human and animal intestinal tract, human mouth and vagina |
38,39 |
Lactobacillus crispatus |
Straight to slightly curled rod cells, 0.8-1.6 by 2.3-11 µm, occur in single or in short chains |
Obligatory homofermentative A few strains can grow at 48-53°C |
Isolated from human faeces, vagina, and buccal cavities |
38 |
Lactobacillus amylovarus |
Rod-shaped cells, 1.0 by 3.0-5.0 µm, existing as single and in short chains |
Obligatory homofermentative Requires pantothenic acid, folic acid, nicotinic acid, and riboflavin for growth |
Pig intestinal epithelial cells |
37
|
Lactobacillus gallinarum |
Shorter to long rod-shaped cells, 0.5-1.5 by1.5-10 µm, existing as single, in pairs, or in short chains. |
Obligatory homofermentative Tolerant to 4% NaCl |
Chicken intestine |
38,40 |
Lactobacillus gasseri |
Rods with rounded end cells, 0.6-.08 by 3.0-5.0 µm, existing in single or in chains (mini-cells and snake formation) |
Obligatory homofermentative Growth is exceptionally expanded by anaerobiosis and 5% CO2 |
Mouth, intestine, faeces, and vagina |
38,41 |
Lactobacillus johnsonii |
Shorter to long rod-shaped cells, 0.5-1.5 by 1.5-10 µm, existing in single, pairs, or in short chains |
Obligatory homofermentative Tolerant to 4% NaCl |
Chicken faeces, mice, calves, and pigs |
38 |
Lactobacillus helveticus |
Rod cells, 0.7-0.9 by 2.0-6.0 µm, existing in single, or in chains |
Obligatory homofermentative Requires thiamine, folic acid, biotin, vitamin B12 for development, a few strains can likewise grow at 50-52 °C |
Sour milk, cheese starter culture, and cheese (emmental and gruyere in particular) |
38 |
Lactobacillus delbrueckii subsp. bulgaricus |
Rods with rounded end cells, 0.5-.08 by 2.0-9.0 µm, existing as single, or in short chains |
Obligatory homofermentative Requires pantothenic acid and niacin. Some strains need riboflavin, folic acid, vitamin BI2, and thymidine. |
Yoghurt and cheese |
38,42 |
Lactobacillus salivarius subsp. salivarius |
Rods cells with rounded ends, 0.6-0.9 by 1.5-5.0 µm, existing as single or in chains with varying length |
Obligatory homofermentative Ferments salicin and esculin |
The intestinal tract of human, hamster, and chicken |
38,43 |
Lactobacillus casei |
Rod-shaped cells, 0.7-1.1 by 2.0-4.0 µm, existing as square ends and tends to form chains |
Facultatively heterofermentative Requires riboflavin, folic acid, calcium pantothenate, and niacin for development, needs pyridoxal or pyridoamine as fundamental or stimulatory growth prerequisite |
Milk, cheese, dairy products, dairy environment, sourdough, cow dung, silage, human intestinal tract, mouth, vagina, and sewage |
38,44 |
Lactobacillus paracasei subsp. paracasei |
Rod-shaped square-ended cells, 0.8-1.0 by 2.0-4.0 µm, existing as single or in chains |
Facultatively heterofermentative Develop at 10 and 40°C a few strains can develop at 5 and 45°C |
Dairy products, sewage, silage, human and clinical sources |
38,45 |
Lactobacillus paracasei subsp. tolerans |
Rod cells with square ends, 0.8-1.0 by 2.0-4.0 µm, existing as single or in chains |
Facultatively heterofermentative Withstand at 72°C for 40 sec |
Dairy products |
38,42 |
Lactobacillus plantarum |
Straight rod cells with rounded ends, 0.9-1.2 by 3.0-8.0 µm, existing as single, in pairs, or in short chains |
Facultatively heterofermentative Require calcium pantothenate and niacin for growth |
Dairy products environments, silage, sauerkraut, pickled vegetables, sourdough, cowdung, the human mouth, intestinal tract, faeces, and from sewage |
38,46 |
Lactobacillus rhamnosus |
Rod-shaped cells with square ends, 0.8-1.0 by 2.0-4.0 µm, existing as single or in chains |
Facultatively heterofermentative Some of the strains grow at 48ºC |
dairy products, sewage, humans, and clinical sources |
38,42 |
Lactobacillus fermentum |
Rod cells, 0.5-0.9 µm, mostly existing in single or in pairs, the length is highly variable |
Obligately heterofermentative Require calcium pantothenate, niacin, and thiamine for growth |
Yeast, milk products, sourdough, fermenting plant material, manure, sewage, and human mouth and faeces |
38 |
Lactobacillus reuteri |
Slightly irregular cells with bend rods and rounded ends, 0.7-1.0 by 2.0-5.0 µm, existing as single, pairs or in small clusturs |
Obligately heterofermentative
|
Human and animal faeces, meat products and sourdough |
38,47 |
Lactobacillus sp. studies in Alzheimer’s disease
The gut microbiota’s contribution to AD pathogenesis is well studied in human and animal models. Most of the studies on probiotics were associated with its effects on oral bacteriotherapy in numerous neurological diseases and function, and only a few examines have been done to find the relationship between probiotic treatment and the mechanisms connected with AD48. The scientists have shown the benefits of probiotics to improve cognitive impairment in humans. The probiotics are hypothesized to be a cognition booster because of its two-way communication between gut microbiota, the GIT, and the brain through the immune system, nervous system, and hormones49. The contribution of Lactobacillus strains to the AD pathogenesis is well depicted in AD models (Table 2).
Table (2):
Lactobacillus sp. study on Alzheimer’s disease.
Lactobacillus sp. used |
Type of study animal/human |
Treatment |
Major findings |
Future aspect or limitation of the study |
Reference |
|---|---|---|---|---|---|
L. helveticus R0052 |
Male Wistar rats |
Peripheral neuroinflammation induced by Lipopolysaccharides (LPS). |
Probiotic treatment showed a decrease in both systemic and neuroinflammation responses stimulated by LPS. Proinflammatory cytokines (TNF-α and IL1-β) levels are significantly decreased in the hippocampus and serum of the model. |
The effects are not observed in the behavioural test, further research is needed to confirm the conclusion |
48 |
L. helveticus |
ddY mice |
Scopolamine induced memory impairment |
Calpis sour milk whey powder (prepared by using L. helveticus and S. cerevisiae) treated mice indicated an improvement in scopolamine-induced memory deterioration and memory of object recognition. |
Can be used as a preventive measure from AD and as a learning and memory enhancer in humans. Further analysis with L. helveticus fermented milk to be done to clarify its potential in the enhancement of cognition in humans. |
50,51 |
L casei W56, L. lactis W19, L. acidophilus W22, L. paracasei W20, L. plantarum W62, and L. salivarius W24 |
Human |
Patients with International Classification of Disease (ICD)-10 criteria of AD (f 00.1). |
Probiotic supplementation results in an increase of kynurenine levels in serum. Stimulation of anergic immune cells may capable to initiate mechanisms that are helpful to eliminate the amyloid aggregates and damaged cells. |
Increased activating events may exert a negative impact on gut barrier function and may stimulate the neurodegenerative process further. The study was not placebo-controlled |
52 |
L. Plantarum MTCC1325 |
Wistar Rats |
D-galactose induced AD |
Activities of membrane transport ATPases were improved significantly. The bacterium stabilized the structural and functional condition of the membranes by controlling the ionic gradient through its antioxidant activity. |
Studies on higher mammalian models like a rabbit, owl monkeys, vervet monkeys, squirrel monkeys should be done to understand better on Lactobacillus strains and its protection against neurodegenerative disease. |
1 |
L. paracasei BD87E6 |
In vitro studies |
L. paracasei BD87E6 used as a biocatalyst. |
(S)-rivastigmine drug synthesized in a mild, cheap, and nature-friendly process using this strain as biocatalyst |
Can be used as an attractive strain for biocatalytic preparation of other carbinols |
20 |
Lactobacillus sp. and other microbial community |
UAS-ArcAβ42 flies and elav-GAL4c155 Drosophila |
Drosophila models were set up by expressing Aβ in the CNS for the investigation of molecular mechanisms of AD. |
The proportion of Lactobacillus and Acetobacter and the production of acetate were remarkably got decreased. A dysregulation in the microbiota can lead to AD by regulating SCFA |
The molecular pathology understanding of AD model can be further used to develop an alternative therapeutic method in the future. |
53 |
L. fermentum, L. Casei, L. acidophilus |
AD patients |
Treating of AD patients with a probiotic formulation containing L. acidophilus, L. casei, L. fermentum, and Bifidobacterium bifidum |
Cognitive signs improved slightly, some antioxidant factors raised and normalization of some lipid profiles. |
The group of AD patients were under the severe stage of disease (83.5 vs. 67%) and less were under moderate stage (16.5 vs. 33%) |
54
|
L. plantarum MTCC 1325 |
Albino rats |
D-galactose induced AD |
Ability to produce the neurotransmitter acetylcholine, healthy neurons with hyperchromatic nuclear chromatin were observed, showed a significant decrease in acetylcholinesterase (AChE) level compared to the AD-model group. |
Compared to the control group, the strain alone could not make any effect on AChE activity. Further investigation on the underlying mechanism of the relationship between L. plantarum MTCC 1325 and AD should be done. |
55,56 |
L. acidophilus CUL60, L. acidophilus CUL21 |
Middle-aged rats |
Aβ (1-4) induced spatial learning impairment by the pre-treatment with L. acidophilus, B. bifidum, and B. longum |
Improved learning impairment, improved cognitive function, |
Probiotic Supplementation did not show an impact on spatial memory |
57,58 |
L. acidophilus |
AD patients |
NINDS-ADRDA criteria and revised criteria from the National Institute of Aging-Alzheimer’s association diagnosed AD patients. |
Probiotic and selenium co-supplementation on AD patients had a favourable effect on MMSE score, hs-CRP, TAC, GSH, insulin metabolism markers, triglycerides, VLDL, LDL, total-/HDL-cholesterol. Also, an improvement in gene expression of TNF-α, PPAR-γ, and LDLR. |
No effect on inflammation biomarkers, oxidative stress, FPG, other lipid profile, and gene expression of IL-8 and TGF-β. Faecal bacterial loads and plasma selenium level quantification by the intake of probiotic and selenium were not accessed and also their co-supplementation on gene expression related to oxidative stress was not examined. |
58 |
Lactobacillus C29 |
Male C57BL/6J mice |
Memory impairment with D-galactose induced aging |
D-galactose excessive intake caused chronic inflammation due to the generation of ROS. Treatment with C29 increased the suppressed expression of DCX, BDNF, and CREB in the hippocampus region of the mouse. The findings of the study suggest that C29 can be used to inhibit inflammaging. |
Suppressed M2 markers arginase 1 and CD206 suggesting that inflammation can be induced by D-galactose by activating M1 macrophages. The expression of autophagy proteins was influenced by neither C29 nor D-galactose. |
59 |
L. fermentum, L. rhamnosus, L. plantarum, L. brevis, L. casei, L. helveticus, L. salivarius, L. sakei, L. reuteri, L. mucosa, L. crispatus, L. buchneri, L. gasseri |
In vitro |
Synthesis of GABA from Lactobacillus and Bifidobacterium strains |
Food derived Lactobacillus strains produced a high amount of GABA (involved in neurotransmission and brain metabolism) (L. buchneri WP2001, L. brevis NCL912, L. brevis K203, and L. plantarum strains). GABA impaired function is involved in AD neuropathy. |
The genes gadB and gadC are required for the synthesis and export of GABA from bacteria. The gadB gene is active in the acidic medium and the gut pH is almost close to neutral. |
60 |
L. helveticus NS8 |
Adult male specific-pathogen-free (SPF) Sprague-Dawley rats |
Chronic restraint stress in rat |
Chronic treatment with the probiotic can leads to an anxiolytic and antidepressant effects, boost cognition, decrease the levels of plasma CORT and ACTH, modulate the balance of anti-inflammation and pro-inflammation, restore the content of 5-HT, NE, BDNF in the hippocampus region. |
The probiotic supplementation can be used as an efficient safe treatment for chronic-stress-induced depression. |
61 |
L. acidophilus, L plantarum, L. paracasei, L. delbrueckii subsp. bulgaricus, L. brevis |
3xTg-ADmice |
AD mice model (reliable model of human AD patients) was treated with nine live strains of bacteria (Lactobacilli, Bifidobacteria, and Streptococcus thermophilus). |
The modification of gut microbiota can affect several pathways and as a result, delays the progression of AD. |
The diminution of Aβ load and cognitive function improvement supports the idea of gut microbiota modulation for the prevention and treatment of AD. |
62 |
L. acidophilus, L. casei, L. fermentum |
AD patients |
Patients are treated with probiotic milk containing L. acidophilus, L. casei, L. fermentum, and Bififobacterium bifidum. |
Consumption of probiotics had favourable effects on MDA, hs-CRP, insulin metabolism markers, serum levels of triglyceride, and VLDL. The probiotic supplements can have clinical significance on the impact of cognitive symptoms. |
Patients cognition was assessed based only on MMSE test. |
63 |
L. fermentum strain NS9 |
Male Sprague-Dawley rats |
Ampicillin induced physiological and psychological irregularity in rats. |
Probiotic supplementation reduced the ampicillin-induced spatial memory deterioration and improved its chronic restraint stress. |
NMDA receptor and MR levels in hippocampus not been measured. |
64 |
The relationship between the brain and the gut is a rapidly emerging field of study due to the importance of a healthy gut specifically for immune systemic functions as well as for mental health. Once the most ignored area (the gut) has now become the most appreciated area because of its effects on most chronic diseases including neurodegenerative diseases. Lactobacillus strains as a probiotic supplement got a long history of safe uses because of their normal inhabit in the gastrointestinal tract of human beings.
The studies on probiotic supplementation with Lactobacillus strains showed a decrease in the neuroinflammation responses stimulated by lipopolysaccharides (LPS) which produce proinflammatory cytokines48. L. plantarum MTCC 1325 was reported to produce acetylcholine (Ach) neurotransmitter which has properties against D-galactose induced AD impairment1. L. paracasei BD87E6 was reported to produce (S)-rivastigmine, an anticholinesterase inhibitor that serves the cholinergic hypothesis20. A dysregulation in the gut microbiota can lead to AD by regulating short-chain fatty acid (SCFA)53. Lactobacillus strains can be used as a preventive measure to treat AD, cognitive enhancer, memory enhancer, and safe treatment for chronic-stress-induced depression. Studies on AD mice models treated with Lactobacillus strains proved that the modification on the gut microbiota can affect the various pathways which can result in the delaying of AD progression. The treatment with probiotic supplements showed a reduction in Aβ load and an improvement in cognitive function which supports the idea of modulation of gut microbiota for the treatment and prevention of AD62.
A study from the University of Geneva, Switzerland confirms the correlation between an imbalance of gut microbiota linked to the Aβ plaques development in the brain65. Studies on the links between metabolic and AD demonstrate an increment in Type 3 diabetes due to the unhealthy nutrigenomic diets down-regulated brain and hepatic Sirt1 (Sirtuin 1) related with insulin resistance, aggregation of α-synuclein and, Aβ dyshomeostasis in AD and PD66. Increased exposure to Gram-negative bacterial derived LPS can cause dysbiosis in gut microbiota which may initiate metabolic and liver diseases and promote systemic chronic low-grade inflammation. In vitro studies on investigating the Lactobacillus and Bifidobacterium probiotics on colonic LPS and inflammatory cytokine concentrations using human colonic microbiota models uncovered that the particular probiotic strains can diminish the concentrations of colonic LPS, which may further reduce the secretion of inflammatory cytokines in macrophage cells67. LPS alters the cell phospholipid dynamics associated with the recruitment of the Aβ peptide with the advancement of toxic Aβ oligomers. With the induction of a neuroinflammatory response, LPS can act on Blood-Brain Barrier (BBB) with BBB disruption or through receptors68. Through the inflammatory process, the bacterial LPS corrupts asterocyte which thus delays Aβ clearance in the brain with an increased amyloid plaque formation in different networks related to excessive feeding and abnormal liver metabolism69. Researchers have been now recognized that the gene Sirt 1 to be defective and has been linked to genetic disease, non-alcoholic fatty liver disease (NAFLD), diabetics, and neurodegenerative diseases and the bacterial LPS may act as a competitive inhibitor to Sirt 1 with glucose and cholesterol toxicity to different cells and tissues70. To reactivate Sirt 1 and to improve drug-induced toxicity nutritional diets are required. For early identification of AD, researchers are working to identify the specific bacterial strains that produce inflammatory LPS and short-chain fatty acids (SCFAs). Understanding these underlying factors may give a new point of view on novel therapeutic strategies for AD and pathologies.
Biotherapy with Lactobacillus strains shows an enormous ability to treat against AD-related pathogenesis. Thus, Modulation of the gut with a personalized diet can become a treatment for various disorders including AD with decreased or no side effects. Further research to confirm the gut-microbiota and related linkages to the gut-brain axis are required to completely understand the scope of probiotics to treat these impaired diseases with a good safety profile. Researchers have been identified the inflammatory molecules LPS, from bacteria been linked to AD and chronic gut inflammation, and SCFAs. The increased degrees of LPS are identified with chronic diseases such as NAFLD, diabetics, obesity, and neurodegenerative disease. The interest in probiotics treatments for AD is quite compelling with importance to its interaction with LPS. LPS is associated with the aggregation of Aβ with impacts on nuclear and cell receptors prompts to neurotoxicity and Aβ plaque formation. In future researchers can contribute to the perspective of probiotic therapy with Lactobacillus strains and interaction with LPS to prevent Aβ aggregation and neurodegeneration as a safe and effective therapy.
ACKNOWLEDGMENTS
We would like to thank the Department of Biotechnology, Karunya Institute of Technology and Sciences.
CONFLICT OF INTEREST
The author declares that their is no conflict of interest.
AUTHORS’ CONTRIBUTION
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.
FUNDING
This research was supported by UGC-Maulana Azad Fellowship, grant number F1-17.1/2016-17/MANF-2015-17-KER-70961.
ETHICS STATEMENT
This article does not contain any studies with human participants or animals performed by any of the authors.
AVAILABILITY OF DATA
All datasets generated or analysed during this study are included in the manuscript.
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