CN114099555A - Lactobacillus plantarum lipoteichoic acid and application thereof in inhibiting amyloid protein aggregation - Google Patents
Lactobacillus plantarum lipoteichoic acid and application thereof in inhibiting amyloid protein aggregation Download PDFInfo
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- CN114099555A CN114099555A CN202111332410.2A CN202111332410A CN114099555A CN 114099555 A CN114099555 A CN 114099555A CN 202111332410 A CN202111332410 A CN 202111332410A CN 114099555 A CN114099555 A CN 114099555A
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- lactobacillus plantarum
- lipoteichoic acid
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Abstract
The invention provides a lactobacillus plantarum lipoteichoic acid and application thereof in inhibiting amyloid protein aggregation. The main chain of the lactobacillus plantarum lipoteichoic acid contains glycerol, and the side chain contains a large amount of N-acetylglucosamine and alanine modification. The lipoteichoic acid can effectively inhibit the aggregation of beta-amyloid 1-42 (Abeta 42), is a potential Abeta 42 aggregation inhibitor, and can be applied to the development of medicaments, health-care products or functional foods for preventing and/or improving Alzheimer's disease.
Description
Technical Field
The invention belongs to the technical field of medicines, health products or foods, and particularly relates to separation and extraction, structure identification and application of novel lactobacillus plantarum lipoteichoic acid in inhibiting amyloid protein aggregation, in particular to application of lactobacillus plantarum MA2 serving as a beta-amyloid 1-42 (Abeta 42) aggregation inhibitor in preparation of medicines, health products and functional foods for preventing and/or improving Alzheimer's disease.
Background
Aggregation and misfolding of amyloid in cells and tissues to form toxic intermediates and amyloid fibrils may lead to various biological dysfunctions. These aggregation intermediates and fibers are presumed to be associated with certain neurodegenerative and other disorders, such as Alzheimer's Disease (AD), Parkinson's Disease (PD), diabetes type II, and the like. Numerous studies have demonstrated that the more toxic moiety is an oligomer or fibril intermediate, and the development of a highly effective amyloid aggregation inhibitor or an anti-amyloid aggregation functional food is one of the effective means for alleviating and treating these diseases. The aggregation and deposition of beta-amyloid 1-42(A beta 42) are closely related to the development of AD, so that the inhibition of the aggregation of the A beta 42 and the depolymerization of the A beta 42 fibers are effective ways for developing anti-AD drugs.
The probiotics is a large number of microorganisms beneficial to human bodies, including lactic acid bacteria, bifidobacteria and the like, and plays a role of probiotics by regulating the intestinal microecological balance. Multiple studies show that the intake of probiotics can increase the adhesion of intestinal flora, effectively improve intestinal microecology, activate immune system, reduce inflammation, promote the release of neurotransmitter and other beneficial metabolites, and further improve AD and other neurodegenerative diseases. After the AD model rat intakes mixed probiotics composed of 4 bacteria such as lactobacillus acidophilus, bifidobacterium lactis and the like, the spatial memory capacity and the oxidative stress of the AD model rat are obviously improved. Clinical trials also evaluated the effect of various probiotics consisting of lactobacilli and bifidobacteria on learning and memory of AD patients, and the results showed that the minimal mental state of the tested patients was significantly improved. Therefore, the microecological therapy for improving the intestinal flora by probiotics is expected to be an effective way for preventing and improving AD. At present, probiotics for preventing and treating AD are known to be deficient, the study difficulty is increased due to the complexity of intestinal flora and metabolites thereof, the action mechanism for improving AD by using intestinal microecology is not clear, and the problems are key scientific problems for preventing and relieving AD by probiotics.
In recent years, the concept of metazoan has been receiving much attention, and metazoan is a general term for a metabolite component and a bacterial body of a probiotic after processing of the probiotic. Research proves that some metazoan have better immunoregulation capability than original viable bacteria and still have high physiological activity even treated by high temperature, ultrasound or gastrointestinal digestive fluid. Among them, teichoic acid is a representative component of metazoan, and is a key for determining the tolerance of metazoan to acid, alkali and heat. Teichoic acid is a specific component of gram-positive bacterial cell wall, and is divided into a main chain and a side chain, wherein the main chain is polymerized by 16-40 phosphoric acid-glycerol or phosphoric acid-ribitol, and the side chain is modified by hydroxyl, N-acetylglucosamine or D-alanine, etc. Teichoic acid can be divided into Lipoteichoic acid (LTA) and teichoic acid (WTA), anchored to peptidoglycan of the cell membrane and cell wall, respectively. Wherein, the gram-positive bacteria lipoteichoic acid has important function for the physiological function, which mainly comprises the following aspects: (1) determining cellular colonization of the bacteria; (2) the balance of anions and cations in the bacterial cell wall is maintained, so that the bacteria are prevented from being damaged by antibacterial peptide, antibiotics and the like; (3) recognizing host cell related receptor and making interaction, specifically recognizing and activating animal mode recognition receptor and inducing correspondent immune response reaction.
The lactobacillus plantarum MA2 is a novel lactobacillus separated from the subject group, and early researches show that the lactobacillus plantarum MA2 has good acid-resistant, cholate-resistant and antioxidant activities and has a remarkable function of improving cognitive dysfunction of AD mice. Meanwhile, the thalli subjected to high-temperature or ultrasonic treatment also has a good effect of improving AD, so that the lactobacillus plantarum MA2 lipoteichoic acid (lpTLA) is separated and extracted for the first time, the structure of the lactobacillus plantarum MA2 lipoteichoic acid (lpTLA) is identified, the effect of the lactobacillus plantarum MA2 lipoteichoic acid on inhibiting Abeta 42 aggregation is explored, and the lactobacillus plantarum lipoteichoic acid has important theoretical significance and application value for researching that the teichoic acid improves neurodegenerative diseases and developing and preventing and/or improving AD medicines, health care products or functional foods.
Disclosure of Invention
The invention provides separation, extraction and structure identification of novel lactobacillus plantarum lipoteichoic acid, application of the novel lactobacillus plantarum lipoteichoic acid in inhibiting amyloid protein aggregation, and application of the novel lactobacillus plantarum lipoteichoic acid in preparing medicaments, health-care products or functional foods for preventing and/or improving AD.
Further, the Lactobacillus plantarum lipoteichoic acid is Lactobacillus plantarum MA2 lipoteichoic acid.
Further, the lactobacillus plantarum MA2 lipoteichoic acid is separated, extracted and structurally identified.
Further, use of Lactobacillus plantarum MA2 lipoteichoic acid in the manufacture of a medicament, health product or functional food for preventing and/or ameliorating a disease characterized by aggregated deposition of A β 42.
Further, the disease is alzheimer's disease.
Further, the Lactobacillus plantarum MA2 lipoteichoic acid was present as an aqueous dispersion.
Further, the Lactobacillus plantarum MA2 lipoteichoic acid was present in an aqueous dispersion at a concentration of 0.25,0.50,1.00,2.00 mg/mL.
The lactobacillus plantarum lipoteichoic acid is lipoteichoic acid which is separated, purified and structurally identified for the first time, also is used for exploring the function of the lactobacillus plantarum lipoteichoic acid in inhibiting A beta 42 aggregation for the first time, and has the following advantages in developing an A beta 42 aggregation inhibitor:
the application of the lactobacillus plantarum MA2 lipoteichoic acid in inhibiting A beta 42 aggregation provided by the invention is derived from lactobacillus plantarum having a probiotic effect on a human body, and is high in safety; the content of N-acetylglucosamine, alanine and fatty acid groups on the side chain of lpLTA obtained by the invention is high, the lpLTA has important effect on the physiological function, can effectively inhibit A beta 42 aggregation, can be used as a potential drug precursor or food functional factor, can be used for developing new drugs, health care products or functional foods, and can be used for preventing and/or improving diseases characterized by A beta 42 aggregation and abnormal conception thereof.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate an embodiment of the invention and, together with the description, serve to explain the invention and not to limit the invention. In the drawings:
FIG. 1 is a chart of the infrared spectrum of Lactobacillus plantarum MA2 lipoteichoic acid (lpLTA) in example 2 of the present invention.
FIG. 2 is a nuclear magnetic resonance hydrogen diagram of Lactobacillus plantarum MA2 lipoteichoic acid (lpLTA) in example 2 of the present invention
FIG. 3 shows fluorescence profiles of ThT cocultured with different concentrations of lipoteichoic acid (lpLTA) from Lactobacillus plantarum MA2 and Abeta 42 according to example 3 of the present invention.
FIG. 4 is an atomic force microscope scan of co-culture of Lactobacillus plantarum MA2 lipoteichoic acid (lpLTA) and A β 42 according to example 4 of the present invention.
Detailed Description
It should be noted that the embodiments and features of the embodiments may be combined with each other without conflict.
The embodiment of the invention provides separation and extraction, structure identification and application in inhibiting amyloid protein aggregation of novel lactobacillus plantarum lipoteichoic acid.
In the embodiment of the invention, the lactobacillus plantarum used is lactobacillus plantarum MA2 separated and screened in the laboratory, is derived from Kefir grains of Tibet farmers, is preserved in China general microbiological culture Collection center (CGMCC 3005) in 2009. Amyloid is β -amyloid 1-42(a β 42), consisting of 42 amino acids, with a molecular weight of about 4.5kDa, containing highly hydrophobic domains, and its aggregation and deposition in nerve cells are closely related to the development and progression of AD. The invention provides the lactobacillus plantarum lipoteichoic acid which can effectively inhibit A beta 42 aggregation, and provides a new thought for the development of an A beta 42 aggregation inhibitor and the research of improving AD by probiotics and metazoans.
The embodiment of the invention provides application of lactobacillus plantarum lipoteichoic acid serving as an Abeta 42 aggregation inhibitor in preparation of drugs, health-care products or functional foods for preventing and/or improving AD. The invention fully utilizes the characteristics of lactobacillus plantarum MA2 lipoteichoic acid as probiotic postbiotic product, high safety, good adaptability of patients and the like, can be widely applied to the development of medicaments, health-care products or functional foods, and further promotes the research progress of AD
Preferably, the Lactobacillus plantarum MA2 lipoteichoic acid is present in an aqueous dispersion. In other words, the Lactobacillus plantarum MA2 lipoteichoic acid can be administered in the form of an aqueous dispersion, such as an injection, an injection solution, a soft capsule, a drink, an oral liquid, etc.
Preferably, the Lactobacillus plantarum MA2 lipoteichoic acid is present in an aqueous dispersion at a concentration of 0.25-2.00 mg/mL. Specific concentrations were 0.25,0.50,1.00 and 2.00 mg/mL.
The isolation, extraction, structural identification and use of a novel class of Lactobacillus plantarum lipoteichoic acids in inhibiting amyloid aggregation are further illustrated below with reference to specific examples.
Example 1: separation, extraction and purification of Lactobacillus plantarum MA2 lipoteichoic acid (lpLTA)
(1) Inoculating lactobacillus plantarum MA2 in a biological safety cabinet, and culturing to an exponential growth phase under corresponding conditions;
(2) taking the bacterial liquid in a centrifuge cup, centrifuging at 4 ℃ and 7000rpm for 20min, collecting thalli, and weighing the wet weight of the thalli;
(3) resuspending wet bacteria in 0.1M sodium citrate buffer solution with pH 4.7 according to a ratio of 1:1(w/v), repeatedly freezing and thawing for 3 times, crushing the bacteria by using an ultrasonic crusher, wherein the amplitude is 30%, the bacteria are opened for 1s and closed for 1s, and the total working time is 30 min;
(4) adding n-butanol of the same volume into the mixed bacterial suspension, mixing thoroughly, stirring on a magnetic stirrer for 30min, centrifuging at 4 deg.C and 7000rpm for 30min, and collecting the lower aqueous phase;
(5) performing rotary evaporation and dialysis on the water phase, wherein the cut-off molecular weight of a dialysis bag is 2000 Da;
(6) preparing a2 x 20cm octyl-Sepharose gel chromatography column, equilibrating the column with 15% n-propanol in 0.1M sodium acetate buffer (pH 4.7);
(7) mixing the lipoteichoic acid crude extract obtained in the step (5) with 0.1M sodium acetate buffer solution (pH 4.7) according to the ratio of 1:5(v/v), diluting and then passing through a column;
(8) washing with 15% n-propanol in 0.1M sodium acetate buffer (pH 4.7) to remove unbound impurities;
(9) gradient eluting the column with 0.1M sodium acetate buffer (pH 4.7) containing 20%, 35%, 45% n-propanol, respectively, and collecting the eluate with 10mL centrifuge tube;
(10) detecting inorganic phosphorus in the eluent, collecting the eluent with higher phosphorus content, and performing rotary evaporation and dialysis;
(11) preparation of DEAE-Fastflow (1.5 x 10cm) anion chromatography column for secondary purification of lipoteichoic acid, column equilibration with 30% n-propanol in 0.1M sodium acetate buffer (pH 4.7);
(12) pretreating the dialyzed sample in the step (10), loading the sample on a column, performing gradient elution by using 0-1M sodium chloride solution (prepared by 0.1M sodium acetate buffer solution), and collecting eluent by using a 10 mL/tube;
(13) performing inorganic phosphorus detection on the eluent collected in the step (12), collecting the eluent with higher phosphorus content, and performing rotary evaporation and dialysis;
(14) freezing the dialysate obtained in (13) at-80 deg.C for 4 hr, lyophilizing to obtain solid of plant lactobacillus MA2 lipoteichoic acid, and freezing for storage.
Example 2: structural identification of Lactobacillus plantarum MA2 lipoteichoic acid (lpLTA)
(1) Infrared spectroscopic analysis
Weighing a proper amount of lpLTA powder, grinding the lpLTA powder and potassium bromide according to the mass ratio of 1:100, tabletting the mixed powder, and analyzing functional groups of lpLTA by using an infrared spectrometer, wherein the result is shown in figure 1.
Referring to FIG. 1, band 3419.95cm-1Characterization of the-NH group, band 2929.31cm-1Characterization of-CH2、-CH3Radical, band 1651.56cm-1Characterization of the-C ═ O group, band 1547.32cm-1Characterization of-C ═ H group, band 1379.09cm-1Characterization of the-P ═ O group, band 1231.18cm-1Characterisation of the sugar residue group, band 1038.81cm-1the-C-O group was characterized. The result is basically consistent with the characteristic functional group of the general structure of lipoteichoic acid, and the infrared spectrum result shows that lpLTA contains a phosphoglycerol structure and groups such as amide and sugar residue.
(2) Nuclear magnetic resonance analysis
A proper amount of lpLTA powder is weighed, fully dissolved by a deuterated reagent, and a sample H spectrum is detected on a 400MHz nuclear magnetic resonance instrument, and the result is shown in figure 2.
Referring to fig. 2, lpLTA has distinct absorption peaks at σ of 5.096,4.182,3.807,3.511,1.983,1.762,1.177 and 0.784, and 5.096ppm is-COO vibration, 4.182 and 3.807ppm are glycerol and glycosyl vibration, 3.511ppm is N-acetyl vibration, and 1.983,1.762,1.177 and 0.784ppm are N-acetylglucosamine, alanine and fatty acid vibration, as seen in conjunction with the standard chemical shift. Therefore, the lpLTA contains glycerol in the main chain and N-acetylglucosamine, alanine and fatty acid modifications in the side chain. Meanwhile, compared with the reported teichoic acid nuclear magnetic resonance results (Wu et al, 2021, Journal of biological Chemistry, 296: 100384; patent application CN 104161776A-lipoteichoic acid from Clostridium butyricum and application thereof in adjusting immune response of livestock and poultry), the nuclear magnetic resonance results in FIG. 2 show that the characteristic peaks of groups with chemical shifts between 0.5 and 2.0ppm are rich, and vibration signals are strong, which indicates that the contents of N-acetylglucosamine, alanine and fatty acid groups on the lpLTA side chain are high, and the nuclear magnetic resonance results have important effects on the physiological functions of the lpLTA side chain.
Example 3: detection of aggregation inhibition effect of Lactobacillus plantarum MA2 lipoteichoic acid (lpLTA) with different concentrations on Abeta 42 by thioflavin T (Thioflavine T, ThT) method
Preparing Abeta 42 solution with the final concentration of 25 MuM, adding lpLTA with the concentration of 0.25,0.50,1.00,2.00mg/mL, adding 25 MuM ThT dye, fully mixing uniformly, placing in an enzyme labeling instrument, continuously culturing at 37 ℃, detecting the fluorescence of the sample every 1h under the detection conditions that the excitation light wavelength is 440nm, the emission light wavelength is 480nm, and the ThT fluorescence result is shown in figure 3.
Referring to FIG. 3, the fluorescence intensity of A β 42 itself gradually increased with time, reaching a plateau substantially after 24h, while the fluorescence intensity of the A β 42 solution also gradually increased with time after 0.25mg/mL of lpTLA was added, but reaching a plateau after 12h, and the maximum fluorescence intensity was about 60% of the maximum fluorescence value of the blank group, indicating that the aggregation of A β 42 was inhibited by lpTLA. After the addition of lpLTA at 0.50,1.00,2.00mg/mL, there was little change in fluorescence intensity of the A β 42 solution, indicating that high concentrations of lpLTA completely inhibited the aggregation of A β 42. As described above, lpTLA has a good effect of inhibiting A β 42 aggregation, and the concentration of lpTLA is 0.50mg/mL, which completely inhibits A β 42 aggregation.
Example 4: observing the effect of Lactobacillus plantarum MA2 lipoteichoic acid (lpLTA) on A beta 42 aggregation to form fibers by using atomic force microscope
A25. mu. M A. beta.42 solution was added with lpLTA at a final concentration of 0.50mg/mL, incubated at 37 ℃ for 48 hours, and examined by atomic force microscopy for the aggregation of A.beta.42 to form fibers in the presence or absence of lpLTA, as shown in FIG. 4,
Referring to FIG. 4, A β 42 was able to aggregate to form a distinct fiber morphology after 48h of self-culture, with a length of between about 200 and 1200 nm. And after 0.50mg/mL lpLTA is added, the aggregation of the A beta 42 is inhibited, no obvious long fiber appears, and further, the lpLTA can effectively inhibit the aggregation of the A beta 42 and is an A beta 42 aggregation inhibitor with great potential.
The application of patent application CN 112386614A-Lactobacillus plantarum MA2 in preparing medicaments or foods for preventing or improving AD is the application of Lactobacillus plantarum MA2, the invention further extracts and identifies lipoteichoic acid of Lactobacillus plantarum MA2 and explores the application of the lipoteichoic acid in inhibiting AD pathogenic protein Abeta 42 aggregation, and the invention has the following advantages: (1) the effect of the lactobacillus plantarum MA2 on relieving AD is demonstrated more deeply and specifically, and theoretical support is provided for researching the action mechanism of the lactobacillus plantarum MA 2; (2)0.5mg/mL lpLTA lipoteichoic acid can completely inhibit the aggregation of Abeta 42, and the lactobacillus plantarum MA2 does not have the function; (3) the lpLTA lipoteichoic acid has stable property, easy storage and low energy consumption in the preparation process; (4) can be added into functional food, beverage, health product, etc. in various forms and accurately in certain amount, and is also helpful for developing anti-AD medicine.
A large number of researches show that the aggregation of A beta 42 is a key factor for the occurrence and development of AD, the inhibition of the aggregation and deposition of the A beta 42 is a hotspot in the current medical field, and the development of new anti-AD drugs is one of effective ways for preventing and treating AD. The lipoteichoic acid of the lactobacillus plantarum MA2 is obtained by ultrasonic crushing, hydrophobic gel filtration chromatography, ion exchange chromatography separation and extraction, the structure of the lipoteichoic acid is preliminarily analyzed through infrared spectroscopy and nuclear magnetic resonance, and the application of the lipoteichoic acid in inhibiting amyloid Abeta 42 aggregation is provided and verified by ThT fluorescent staining and atomic force microscope analysis. The present invention has been described in terms of embodiments, and it will be apparent to those of ordinary skill in the art that variations or modifications and combinations of the methods herein can be made to implement the techniques of the present invention without departing from the spirit and scope of the invention. It should be understood that the above description is only exemplary of the preferred embodiment of the present invention, and is not intended to limit the invention, and that all similar substitutes and modifications apparent to those skilled in the art, which fall within the spirit and scope of the invention, are deemed to be within the spirit, scope and content of the invention.
Claims (9)
1. The lactobacillus plantarum lipoteichoic acid is characterized in that a main chain of the lactobacillus plantarum lipoteichoic acid contains glycerol, and a side chain contains a large amount of N-acetylglucosamine and alanine modification.
2. A Lactobacillus plantarum lipoteichoic acid according to claim 1, characterized in that: the lactobacillus plantarum is prepared by using lactobacillus plantarum MA2 which is obtained by separating and screening lactobacillus plantarum in the laboratory and originates from Kefir grains in Tibetan farmers, and the lactobacillus plantarum MA2 is preserved in China general microbiological culture Collection center (CGMCC) with the preservation number of CGMCC 3005.
3. The Lactobacillus plantarum lipoteichoic acid according to claim 1, the preparation process comprises separation, extraction, and purification processes, and is characterized by comprising the following specific steps:
(1) inoculating Lactobacillus plantarum MA2 in MRS liquid culture medium in a biological safety cabinet, and culturing in an incubator at 37 deg.C for 16-20 h;
(2) taking the bacterial liquid obtained in the step (1) in a centrifuge cup, centrifuging for 20min at 4 ℃ and 7000rpm, collecting thalli, and weighing the wet weight of the thalli;
(3) resuspending wet bacteria in 0.1M sodium citrate buffer solution with pH 4.7 according to a ratio of 1:1(w/v), repeatedly freezing and thawing for 3 times, crushing bacteria by using an ultrasonic crusher to obtain mixed bacteria suspension, wherein the amplitude is 30%, the opening time is 1s, the closing time is 1s, and the total working time is 30 min;
(4) adding n-butanol with the same volume into the mixed bacterial suspension obtained in the step (3), fully mixing, stirring on a magnetic stirrer for 30min, centrifuging at 4 ℃ and 7000rpm for 30min, and gently collecting the lower-layer water phase;
(5) performing rotary evaporation and dialysis on the water phase, and intercepting lipoteichoic acid with molecular weight of 2000Da by a dialysis bag to obtain a lipoteichoic acid crude extract;
(6) preparing a2 x 20cm octyl-Sepharose gel chromatography column, equilibrating the column with 0.1M sodium acetate buffer, pH 4.7, containing 15% n-propanol;
(7) mixing and diluting the lipoteichoic acid crude extract obtained in the step (5) and 0.1M sodium acetate buffer solution with the pH value of 4.7 according to the volume ratio of 1:5, and then passing through a column;
(8) washing with 15% n-propanol in 0.1M sodium acetate buffer solution of pH 4.7 to remove impurities which cannot be combined;
(9) gradient eluting the column with 20%, 35%, 45% n-propanol in 0.1M sodium acetate buffer solution of pH 4.7, and collecting the eluate with 10mL centrifuge tube;
(10) detecting inorganic phosphorus in the eluent, collecting the eluent with higher phosphorus content, and performing rotary evaporation and dialysis;
(11) preparation of DEAE-Fastflow 1.5 x 10cm anion chromatography column secondary purification of lipoteichoic acid, pH 4.7 containing 30% n-propanol 0.1M sodium acetate buffer balance column;
(12) pretreating the dialyzed eluent in the step (10), loading the dialyzed eluent into a column, performing gradient elution by using 0-1M sodium chloride solution, and collecting the eluent by using a 10 mL/tube; preparing a sodium chloride solution 0.1M sodium acetate buffer solution;
(13) performing inorganic phosphorus detection on the eluent collected in the step (12), collecting the eluent with higher phosphorus content, and performing rotary evaporation and dialysis;
(14) freezing the dialysate obtained in (13) at-80 deg.C for 4 hr, lyophilizing to obtain solid of plant lactobacillus MA2 lipoteichoic acid, and freezing for storage.
4. Use of a lipoteichoic acid of lactobacillus plantarum according to claim 1 for inhibiting amyloid aggregation.
5. The use of a lipoteichoic acid of lactobacillus plantarum as claimed in claim 4 for inhibiting amyloid aggregation, characterized in that: the application of the beta-amyloid peptide in preparing medicines, health products or functional foods for preventing and/or improving diseases characterized by the aggregation and deposition of beta-amyloid 1-42 (Abeta 42).
6. Use according to claim 5, characterized in that: the disease is alzheimer's disease.
7. Use according to claim 5, characterized in that: the Lactobacillus plantarum MA2 lipoteichoic acid is present in an aqueous dispersion.
8. Use according to claim 5, characterized in that: the Lactobacillus plantarum MA2 lipoteichoic acid was present in an aqueous dispersion at a concentration of 0.25,0.50,1.00,2.00 mg/mL.
9. The use according to claim 7, wherein said aqueous dispersion of lipoteichoic acid from Lactobacillus plantarum MA2 is formulated for injection, soft capsule, beverage or oral liquid.
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