WO2012107601A1 - Utilisation d'une souche de lactobacillus bulgaricus pour le traitement de l'immunosénescence - Google Patents

Utilisation d'une souche de lactobacillus bulgaricus pour le traitement de l'immunosénescence Download PDF

Info

Publication number
WO2012107601A1
WO2012107601A1 PCT/ES2011/000329 ES2011000329W WO2012107601A1 WO 2012107601 A1 WO2012107601 A1 WO 2012107601A1 ES 2011000329 W ES2011000329 W ES 2011000329W WO 2012107601 A1 WO2012107601 A1 WO 2012107601A1
Authority
WO
WIPO (PCT)
Prior art keywords
strain
probiotic
increase
bulgaricus
lymphocytes
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/ES2011/000329
Other languages
English (en)
Spanish (es)
Other versions
WO2012107601A8 (fr
Inventor
José Miguel DE LAS HERAS DEL RIO
Maria Baltadjieva
Carlos LOPEZ LARREA
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of WO2012107601A1 publication Critical patent/WO2012107601A1/fr
Anticipated expiration legal-status Critical
Publication of WO2012107601A8 publication Critical patent/WO2012107601A8/fr
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; PREPARATION THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/127—Fermented milk preparations; Treatment using microorganisms or enzymes using microorganisms of the genus lactobacteriaceae and other microorganisms or enzymes, e.g. kefir, koumiss
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/11—Lactobacillus
    • A23V2400/123—Bulgaricus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K2035/11—Medicinal preparations comprising living procariotic cells
    • A61K2035/115—Probiotics
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/225—Lactobacillus

Definitions

  • the present invention relates to the use of a strain of Lactobacillus bulgaricus for the preparation of a drug or food supplement intended for the treatment of immunosenecence or deterioration of the defensive capacity of the immune system as a consequence of chronological aging. Specifically, it refers to the use of the strain of Lactobacillus delbrueckii subsp. bulgaricus, isolated in the mountains of Bulgaria and deposited in the "National Bank for Industrial Microorganisms and Cell Cultures" (NBIMCC) under n ° 8481.
  • NBIMCC National Bank for Industrial Microorganisms and Cell Cultures
  • Probiotics are non-pathogenic microorganisms that exert a positive influence on the health or physiology of the host when ingested.
  • beneficial properties of these microorganisms is their immunomodulatory activity.
  • This process is mainly characterized by (1) the limitation of the repertoire of the T lymphocytes and the accumulation of oligoclonal effector memory cells directed against ubiquitous infectious agents; (2) thymic involution and disappearance of "na ' ⁇ ve"cells; and (3) a chronic inflammatory state.
  • Lactobacillus Among the probiotic organisms inherent to the digestive system of humans, the effect of Lactobacillus is known, presenting an effect on lactose intolerance, effect on the immune system, etc., due to its ability to control infections while maintaining an adequate balance in the microflora of the intestine.
  • Different strains of Lactobacillus have been used for the preparation of products with adequate organoleptic properties and with prophylactic and therapeutic characteristics.
  • the application of the known strains of Lactobacillus delbrueckii subsp. bulgaricus has been limited to the area of fermented milk products and its activity is limited to a short period of time.
  • the patents BG63961, BG63962 and BG63963 disclose that strains of Lactobacillus delbrueckii subsp. bulgaricus are used as crops for Bulgarian yogurt and other fermented dairy products.
  • the patent BG61476 discloses the possibility of combining a biologically active substance from the culture of Lactobacillus delbrueckii subsp. bulgaricus with natural products for the preparation of food additives.
  • Patents UA63201, UA63202 and UA64163 disclose that a strain of Lactobacillus delbrueckii subsp. bulgaricus 9702 grown under certain conditions produces a substance with hepatoprotective, gastroenterological and immune system modulating properties, but does not describe specific clinical experimental data that supports this claim.
  • Lactobacillus delbrueckii subsp. Strain is described in patent application WO2008 / 043161.
  • Bulgaricus deposited in the "National Bank for Industrial Microorganisms and Cell Cultures" (NBIMCC) under n ° 8481, and is indicated in a general way that can be used for the preparation of pharmaceutical or food products with prophylactic and therapeutic properties, showing effect at the local level of the digestive system.
  • NBIMCC National Bank for Industrial Microorganisms and Cell Cultures
  • the present invention relates to the use of the strain of Lactobacillus delbrueckii subsp. bulgaricus, deposited in the "National Bank for Industrial Microorganisms and Cell Cultures" (NBIMCC) under n ° 8481 for the preparation of drugs or food supplements intended for the treatment of immunosenescence or deterioration of the defensive capacity of the immune system due to chronological aging . As a consequence of age, a series of changes in the functioning of the immune system that imply a worse defensive capacity can be observed.
  • NBIMCC National Bank for Industrial Microorganisms and Cell Cultures
  • the pharmaceutical or food product prepared from this probiotic strain can be a tablet or capsule for oral administration to the patient.
  • each capsule contains 400 mg of the probiotic strain.
  • the pharmaceutical or food product can also be presented in the form of envelopes.
  • the administration of a drug containing this probiotic strain has been shown to have implications for a number of modifications in both the innate and adaptive immune responses.
  • the probiotic strain acts on different parameters such as:
  • SIRT1 protein sirtuin-1
  • the probiotic strain has an effect on the production of ⁇ -defensins, molecules that represent a defensive first line against bacteria and viruses.
  • - Figure 2 is a graphic representation of the distributions of CD8 + CD28 + CD8 + CD28 + CD28 + T lymphocytes in the probiotic group and placebo at zero time, three and six months after the ingestion of the probiotic.
  • FIG. 3 shows the distribution of different subpopulations in both TCD4 + and CD8 + lymphocytes in young and elderly individuals.
  • FIG. 4 is a graphic representation of the evolution of the frequency of populations of CD4 and CD8 T lymphocytes of the probiotic group
  • Figure 5 represents the population of CD45RA + cells in young and old.
  • FIG. 6 shows the evolution of CD4 + CD45RA + / CD31 + T lymphocyte populations in five individuals representative of the probiotic group and the placebo group.
  • FIG. 7 shows the population of ⁇ -defensins of the probiotic group and placebo group at zero, three and six months of the probiotic intake.
  • FIG. 8 shows levels of SIRT1 mRNA from the probiotic group and placebo at different times of probiotic intake.
  • FIG. 9 shows two 2D-PAGE gels (two-dimensional polyacrylamide electrophoresis), before (9a) and after (9b) of the probiotic intake.
  • the objective of the study on the immune system was to assess the efficacy of the intake of capsules of Lactobacillus delbrueckii subsp. lyophilized bulgaricus in the potentiation of the immune response in the elderly.
  • the main objective was to study the improvement that the exposure to the Lactobacillus delbrueckii subsp strain produces on different aspects of the immune response. bulgaricus in people older than 65 years.
  • Placebo group group of individuals given placebo capsules, without probiotic
  • IRP Immunological risk profile
  • T lymphocytes can be divided into: na ' ⁇ ve (NAIVE, CD45RA + CCR7 +), central memory (CM; CD54RA-CCR7 +), effector memory (E; CD45RA + CCR7) -) and terminally differentiated effector memory (EMRA, CD45RA + CCR7-).
  • NAIVE CD45RA + CCR7 +
  • CM central memory
  • E effector memory
  • EMRA terminally differentiated effector memory
  • CD45RA + cells the expression of CD31 is related to a higher degree of immaturity, this phenotype corresponding to the cells of more recent thymic migration. As can be seen in the representative figure 5, young individuals have this population clearly increased compared to the older individuals.
  • Defensins are cysteine proteins rich in ions, they are found in vertebrates and invertebrates and function as natural antibiotics that are found on the surface of the skin. They are active against bacteria, fungi and viruses. Most defensins act by penetrating the microbial plasma membrane, once they have penetrated, they form a pore that produces cell death.
  • Defensins are peptides highly conserved in the evolutionary scale forming part of the innate immune response, they have a size of 2-5 kilodaltons (typically 30-45 amino acids) and have three disulfide bridges. In humans, they are synthesized mainly in epithelia and leukocytes. Its antimicrobial properties are broad spectrum (antibacterial, antifungal, antiviral) varying in microbicidal effectiveness according to its structure and net cationic charge. According to their molecular pattern of disulfide bridges and genomic distribution they are classified into the alpha (a), beta ( ⁇ ) and theta ( ⁇ ) families.
  • the a-defensins 1-4 have anti-HIV activity and it has been shown that although they have the property of binding to the C1q peptide and thus activating the classical pathway of the complement system. Additionally they have a chemotactic effect for T lymphocytes, monocytes and mature dendritic cells, in addition to inducing the synthesis of cytokines. In this study, no difference was found in the expression of a-defensin 1, neither in the people who took the placebo nor in those who took the probiotic. It is hypothesized that ⁇ -defensins block late events of the replication of viruses and other pathogens. They induce intracellular signals by interacting with chemokine receptors and Toll-like receptors (TLRs), whose pathways promote adaptive immune responses by recruiting dendritic cells and T to the site of invasion.
  • TLRs Toll-like receptors
  • SIRT1 Sirtuin-1
  • SIRT1 is the most studied member of the sirtuin family with respect to increased longevity and age-related diseases. It is believed that it plays a crucial role in the aging process for several reasons. SIRT1 is decreased in senescent cells and in aging. Caloric reduction, clearly related to longevity, induces the production of SIRT1, possibly increasing cell survival. The increase in its expression is also related to the increase in mitochondrial biogenesis, which is closely related to longevity and aging. One activator of SIRT1 is resveratrol whose beneficial effects on cell rejuvenation have been shown to be mediated by the increase in SIRT1.
  • proteomics is the large-scale study of proteins, particularly their structure and function.
  • the proteome is the complete complement of proteins, including the modifications made in a particular set of proteins, produced by an organism or system.
  • Figure 2 shows two 2D-PAGE gels (two-dimensional polyacrylamide electrophoresis) before and after the probiotic intake.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Polymers & Plastics (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Nutrition Science (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Virology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention se rapporte à l'utilisation d'une souche de Lactobacillus delbrueckii subsp. Bulgaricus pour la préparation d'un médicament ou d'un complément alimentaire pour le traitement de l'immunosénescence ou de la dégradation du système immunitaire résultant du vieillissement chronologique. Ladite souche produit des effets au niveau systémique, et aussi bien sur la réponse immunitaire innée que sur la réponse immunitaire adaptative.
PCT/ES2011/000329 2011-02-09 2011-11-11 Utilisation d'une souche de lactobacillus bulgaricus pour le traitement de l'immunosénescence Ceased WO2012107601A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ESP201100133 2011-02-09
ES201100133A ES2386914B1 (es) 2011-02-09 2011-02-09 Uso de una cepa de lactobacillus bulgaricus para el tratamiento de la inmunosenescencia.

Publications (2)

Publication Number Publication Date
WO2012107601A1 true WO2012107601A1 (fr) 2012-08-16
WO2012107601A8 WO2012107601A8 (fr) 2013-09-12

Family

ID=46638155

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/ES2011/000329 Ceased WO2012107601A1 (fr) 2011-02-09 2011-11-11 Utilisation d'une souche de lactobacillus bulgaricus pour le traitement de l'immunosénescence

Country Status (2)

Country Link
ES (1) ES2386914B1 (fr)
WO (1) WO2012107601A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103897998A (zh) * 2012-12-25 2014-07-02 北京中天神舟航天食品技术研究院 唾液乳杆菌及其应用以及功能食品组合物及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE202005009120U1 (de) * 2005-06-10 2005-11-10 Peterik, Josef Bifidoaktiver probiotischer Joghurt
WO2008002484A2 (fr) * 2006-06-23 2008-01-03 Lacpro Industries, Llc Nouvelle souche de lactobacillus bulgaricus et compositions la contenant
WO2008043161A1 (fr) * 2006-10-09 2008-04-17 Maria Baltadjieva Souche probiotique du lactobacille delbrueckii subsp. bulgaricus

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE202005009120U1 (de) * 2005-06-10 2005-11-10 Peterik, Josef Bifidoaktiver probiotischer Joghurt
WO2008002484A2 (fr) * 2006-06-23 2008-01-03 Lacpro Industries, Llc Nouvelle souche de lactobacillus bulgaricus et compositions la contenant
WO2008043161A1 (fr) * 2006-10-09 2008-04-17 Maria Baltadjieva Souche probiotique du lactobacille delbrueckii subsp. bulgaricus

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CANDORE, G. ET AL.: "Immunosenescence and anti-immunosenescence therapies: the case of probiotics", REJUVENATION RESEARCH, vol. 11, no. 2, 2008, pages 425 - 432 *
IBRAHIM, F. ET AL.: "Probiotics and immunosenescence: cheese as a carrier", FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, vol. 59, no. 1, June 2010 (2010-06-01), pages 53 - 59 *
MAKINO, S. ET AL.: "Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1", BRITISH JOURNAL OF NUTRITION, vol. 104, no. 7, October 2010 (2010-10-01), pages 998 - 1006 *
MANE, J. ET AL.: "A mixture of Lactobacillus plantarum CECT 7315 and CECT 7316 enhances systemic immunity in elderly subjects. A dose-response, double-blind, placebo-controlled, randomized pilot trial.", NUTRICION HOSPITALARIA: ORGANO OFICIAL DE LA SOCIEDAD ESPANOLA DE NUTRICION PARENTERAL Y ENTERAL, vol. 26, no. 1, January 2011 (2011-01-01), pages 228 - 235 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103897998A (zh) * 2012-12-25 2014-07-02 北京中天神舟航天食品技术研究院 唾液乳杆菌及其应用以及功能食品组合物及其制备方法

Also Published As

Publication number Publication date
ES2386914A1 (es) 2012-09-05
ES2386914B1 (es) 2013-06-19
WO2012107601A8 (fr) 2013-09-12

Similar Documents

Publication Publication Date Title
ES2705157T3 (es) Composiciones que comprenden cepas bacterianas
Geddes et al. Unleashing the therapeutic potential of NOD-like receptors
Guryanova et al. Strategies for using muramyl peptides-modulators of innate immunity of bacterial origin-in medicine
ES2389547B1 (es) Bifidobacterium cect 7765 y su uso en la prevención y/o tratamiento del sobrepeso, la obesidad y patologías asociadas.
TWI797067B (zh) 包含細菌菌株之組合物
ES2916601T3 (es) Composiciones que comprenden cepas bacterianas
ES2436251B1 (es) Bacteroides cect 7771 y su uso en la prevención y tratamiento de sobrepeso, obesidad y alteraciones metabólicas e inmunológicas.
JP6442401B2 (ja) プロバイオティクスを封入するための微粒子、この微粒子を得ることおよびその使用
KR20050109928A (ko) 유산균으로부터 유래된 소염 활성
BRPI0616960A2 (pt) uso de lactobacilo para o tratamento de infecções virais
JP7490554B2 (ja) 免疫チェックポイント阻害療法を促進するための組成物
JP2023510158A (ja) 細菌及び微生物細胞外小胞を含有する固形剤形
CN105229142A (zh) 免疫刺激剂
ES2734550T3 (es) Composiciones y métodos relacionados con el tratamiento de enfermedades
ES2336222T3 (es) Una composicion que tiene actividades inmunorreguladoras que comprende lactobacillus pensosus.
ES2321602T3 (es) Composicion para fomentar la proliferacion de lactobacillus casei subsp.casei.
US20250121013A1 (en) Use of bacillus amyloliquefaciens for preventing and treating parkinson's disease
WO2005018542A2 (fr) Utilisation de lactoferrine dans une prophylaxie dirigee contre une infection et/ou contre une inflammation, chez des patients immunosupprimes
ES2331863B1 (es) Bacterias y productos derivados para fortalecer las defensas y reducir el riesgo de enfermedad.
WO2020067422A1 (fr) Composition permettant d'activer des lymphocytes t
ES2386914B1 (es) Uso de una cepa de lactobacillus bulgaricus para el tratamiento de la inmunosenescencia.
US20050265963A1 (en) Immunodynamic complexes and methods for using and preparing such complexes
CN115515600B (zh) 免疫功能兴奋用组合物
CN111481565B (zh) 戈氏副拟杆菌的脂多醣用于抑制发炎反应的医药组合物的用途
JP2004262773A (ja) 免疫機能改善を目的としたビフィズス菌製剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 11858031

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 11858031

Country of ref document: EP

Kind code of ref document: A1