WO2024070185A1 - Biomarqueur et procédé pour aider à déterminer le risque d'apparition de l'acné - Google Patents
Biomarqueur et procédé pour aider à déterminer le risque d'apparition de l'acné Download PDFInfo
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- WO2024070185A1 WO2024070185A1 PCT/JP2023/027791 JP2023027791W WO2024070185A1 WO 2024070185 A1 WO2024070185 A1 WO 2024070185A1 JP 2023027791 W JP2023027791 W JP 2023027791W WO 2024070185 A1 WO2024070185 A1 WO 2024070185A1
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- Prior art keywords
- acne
- biomarker
- bacteria
- total
- risk
- Prior art date
Links
- 239000000090 biomarker Substances 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims description 26
- 208000002874 Acne Vulgaris Diseases 0.000 claims abstract description 96
- 206010000496 acne Diseases 0.000 claims abstract description 96
- 241000186427 Cutibacterium acnes Species 0.000 claims abstract description 45
- 241000894006 Bacteria Species 0.000 claims description 48
- 229940055019 propionibacterium acne Drugs 0.000 claims description 23
- 241000894007 species Species 0.000 claims description 7
- 210000001061 forehead Anatomy 0.000 claims description 5
- 239000000853 adhesive Substances 0.000 description 5
- 230000001070 adhesive effect Effects 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 108020004465 16S ribosomal RNA Proteins 0.000 description 2
- 241000625996 Cutibacterium acnes subsp. elongatum Species 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 210000001331 nose Anatomy 0.000 description 2
- 229920000742 Cotton Polymers 0.000 description 1
- 238000007400 DNA extraction Methods 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 239000012790 adhesive layer Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 210000005000 reproductive tract Anatomy 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 238000003696 structure analysis method Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
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- 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, e.g. protozoa; 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6888—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
Definitions
- the present invention relates to a biomarker and a diagnosis assistance method.
- Cutibacterium acnes is the most predominant bacterial species on the skin and plays a central role in the development of acne (see Non-Patent Document 1). It is preferable to be able to accurately know the risk of developing acne in advance, since this would allow treatment to be started early to improve the condition of the body, such as the skin.
- the present invention aims to provide biomarkers that can be used to determine the risk of developing acne.
- a biomarker that can be used to determine the risk of developing acne.
- the biomarker is Propionibacterium acnes type III.
- This embodiment can be used to accurately assess the risk of developing acne.
- 1 is a graph showing the ratio of Propionibacterium acnes to total bacteria in subjects with and without acne. 1 is a graph showing the proportion of Propionibacterium acnes among all bacteria by age group. 1 is a graph showing the log copy number of total Propionibacterium acnes per 6.4 mm2 sample in "acne" and "non-acne” cases. 6. A graph showing the log copy number of total P. acnes per 4 mm2 sample by age group. 1 is a graph showing the composition of Propionibacterium acnes types in all subjects. 1 is a graph showing the composition of acne bacteria types by age group.
- the biomarker of the present invention can be used to determine the risk of developing acne.
- the biomarker of the present invention is Propionibacterium acnes type III.
- P. acnes is genetically classified into five subclasses, namely, types IA1, 1A2, 1B, II, and III. According to the study by the present inventors, it was found that subjects who complain of acne symptoms tend to have a higher proportion of P. acnes in the total bacteria contained in samples collected from the subjects and a lower proportion of type III P. acnes in the total bacteria, compared to subjects who do not complain of symptoms. Therefore, it is believed that the risk of developing acne can be accurately determined by using type III Propionibacterium acnes as a biomarker.
- the ratio of the biomarker of the present invention (type III acne bacteria) to the total acne bacteria contained in a sample (hereinafter simply referred to as "sample") collected from a subject is within a predetermined range, it can be used to determine a high risk of developing acne.
- the specific value of the predetermined range is preferably less than 2%, more preferably less than 1.5%, and even more preferably 0.1% or more and less than 1%. In this way, subjects with a low ratio of biomarkers can be determined to have a high probability of developing acne.
- the ratio of the biomarkers is within the above range and the ratio of the total P. acnes in the total bacteria contained in the sample is within a predetermined range, it can be used to determine that the risk of developing acne is high, thereby making it possible to further increase the accuracy of the above determination.
- a specific value of the predetermined range is preferably 45% or more, more preferably 45% to 70% and even more preferably 50% to 65%.
- the ratio of the biomarker when the ratio of the biomarker is within the above range and the logarithmic copy number of all P. acnes contained in the sample per 6.4 mm2 is within a predetermined range, it can be used to determine that the risk of developing acne is high. This can further increase the accuracy of the above determination.
- the logarithm is a common logarithm with the base "10".
- the specific value of the predetermined range is preferably 3.75 or more, more preferably 3.9 to 4.5, and even more preferably 4.05 to 4.3.
- the site from which the sample is taken from the subject is not particularly limited, and may be any site that is in contact with the external environment, such as the skin, digestive tract, oral cavity, nasal cavity, respiratory tract, and genital tract.
- the site from which the sample is taken is preferably the skin of the subject. If it is the skin of the subject, it is easy to take a sample suitable for determining the risk of developing acne.
- the skin may be any part of the skin, but is preferably at least one of the forehead, cheeks, chin, nose and neck, and more preferably the forehead, since samples taken from these areas can provide results that more accurately reflect the risk of developing acne.
- the diagnosis assistance method of the present invention is a method for assisting in the diagnosis of the risk of developing acne.
- Such a judgment assistance method includes an identification step and a specification step. Each step will be described below in order.
- the identification step involves identifying the species and types of all bacteria present in the sample taken from the subject.
- Preferred sites for collection of samples from subjects are as described above.
- the sample can be collected, for example, by attaching an adhesive (adhesive patch, adhesive sheet, etc.) to the collection site and transferring the sample to the adhesive layer, or by wiping the surface of the collection site with a cotton swab.
- an adhesive adheresive patch, adhesive sheet, etc.
- various methods utilizing lipase or gene characteristics can be used to identify the species and types of all bacteria contained in a sample, it is preferable to combine a microbiome analysis method based on the 16S rRNA gene with a subtype structure analysis method based on a gene of Propionibacterium acnes. By using such a method, the species and types of all bacteria can be accurately identified.
- the proportion of type III acne bacteria in the total acne bacteria is identified. This can be obtained by dividing the number of type III acne bacteria by the total number of acne bacteria based on the results of the total species and types of bacteria identified in the identification step.
- the proportion of type III acne bacteria may be a result obtained from a sample collected from one collection site, or may be an average value of the results obtained from samples collected from multiple collection sites. If the ratio is less than 2% (preferably less than 1.5%, more preferably 0.1% or more and less than 1%), it is preferable to judge that the risk of developing acne is high while also referring to the subject's medical interview, skin photos, etc. In other words, if the ratio of type III acne bacteria to all acne bacteria is less than 2%, it can be assisted in judging that the risk of developing acne is high.
- the identification step it is preferable to further identify whether the ratio of all P. acnes to all bacteria is 45% or more (preferably 45% or more and 70% or less, more preferably 50% or more and 65% or less). In this case, it is possible to more accurately determine whether the risk of developing acne is high. In addition, in the identification step, it is preferable to further identify whether the log copy number of all Propionibacterium acnes contained in the sample per 6.4 mm2 is 3.75 or more (preferably 3.9 to 4.5, more preferably 4.05 to 4.3). This also helps to more accurately determine whether the risk of developing acne is high.
- the risk of developing acne can be accurately determined, which has the advantage that treatment for improving the condition of the body, such as the skin, can be started at an early stage. Furthermore, it may be provided in the following aspects:
- a biomarker that can be used to determine the risk of developing acne the biomarker being type III Propionibacterium acnes.
- a biomarker as described in (1) above which is used to determine that a subject is at high risk of developing acne if the proportion of the biomarker in the total amount of P. acnes bacteria contained in a sample collected from the subject is less than 2%.
- a method for assisting in determining the risk of developing acne comprising an identification step and a specification step, in which the identification step identifies the species and type of all bacteria contained in a sample collected from a subject, and the specification step identifies the proportion of type III acne bacteria among all acne bacteria.
- a method for determining that the risk of developing acne is high when the proportion of type III acne bacteria in the total acne bacteria is less than 2% in the identification step in the method for determining that the risk of developing acne is high in the method for determining that the risk of developing acne is high in the method for determining that the proportion of type III acne bacteria in the total acne bacteria in the identification step is less than 2%.
- step of identifying further includes identifying whether the proportion of the total P. acnes bacteria in the total bacteria is 45% or more.
- step of identifying further includes identifying whether or not the log copy number of the total Propionibacterium acnes contained in the sample per 6.4 mm2 is 3.75 or more. Of course, this is not the case.
- Facial skin conditions were obtained from these subjects using a web questionnaire and smartphone photos.
- a skin surface sample was taken using an adhesive patch (manufactured by TAK-Circulator, Inc., "MySkin") as an adhesive, and the sample was mailed directly to the subjects.
- MySkin an adhesive patch
- the sample was taken from the skin surface of the cheek, and for subjects with acne, the sample was taken from the skin surface of the area with acne (cheek, forehead, chin, around the mouth).
- microbiome analysis based on the 16S rRNA gene and type structure analysis based on a single gene of P. acnes were performed.
- FIG. 1 The ratio of Propionibacterium acnes to all bacteria is shown by age group in the following Table 3 and Figure 2.
- Figure 2 is a graph showing the ratio of Propionibacterium acnes to all bacteria by age group. As a result, the proportion of Propionibacterium acnes among all bacteria was low in the older age group, consistent with previous reports. There was also a significant difference (p ⁇ 0.05) between those in their 20s and 40s.
- Table 4 below and Figure 3 show the log copy number of total P. acnes contained in samples per 6.4 mm2 for "acne” and “non-acne”.
- Figure 3 is a graph showing the log copy number of total P. acnes contained in samples per 6.4 mm2 for "acne” and "non-acne”.
- the logarithmic copy number of all P. acnes was 4.117 in the "with acne” group and 3.722 in the "without acne” group, which was significantly (p ⁇ 0.001) higher than the "without acne” group.
- Table 5 and Figure 4 below show the log copy number of all P. acnes contained in samples per 6.4 mm2 by age group.
- Figure 4 is a graph showing the log copy number of all P. acnes contained in samples per 6.4 mm2 by age group. As a result, the log copy number of all P. acnes was lower in the older age group, consistent with previous reports. In addition, significant differences (p ⁇ 0.05) were observed between those in their 20s and 30s, and between those in their 20s and 40s.
- Fig. 5 is a graph showing the composition of types of Propionibacterium acnes in all subjects. The results showed that type IA1 was the most common at 42.8%, followed by type IA2 at 24.5%, type II at 21.5%, type IB at 10.1%, and type III at 1.1%.
- Fig. 11 is a graph showing the composition of types of Propionibacterium acnes in subjects by age group. As a result, the composition of acne bacteria types was similar across all age groups.
- type III P. acnes is suitable for use as a biomarker to determine the risk of developing acne.
- IA1 Type IA1 IA2: Type IA2 IB: Type IB II: Type II III: Type III
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- Proteomics, Peptides & Aminoacids (AREA)
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- Urology & Nephrology (AREA)
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Abstract
La présente invention vise à procurer un biomarqueur utilisable pour déterminer le risque d'apparition de l'acné. La solution selon la présente invention porte sur un biomarqueur qui peut être utilisé pour déterminer le risque d'apparition de l'acné. Le biomarqueur est le Cutibacterium acnes de type III.
Applications Claiming Priority (2)
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JP2022-158576 | 2022-09-30 | ||
JP2022158576 | 2022-09-30 |
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WO2024070185A1 true WO2024070185A1 (fr) | 2024-04-04 |
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PCT/JP2023/027791 WO2024070185A1 (fr) | 2022-09-30 | 2023-07-28 | Biomarqueur et procédé pour aider à déterminer le risque d'apparition de l'acné |
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014095608A (ja) * | 2012-11-09 | 2014-05-22 | Nippon Menaade Keshohin Kk | 皮膚に常在するアクネ菌の菌数を予測する方法 |
JP2016528880A (ja) * | 2013-06-18 | 2016-09-23 | プロダームアイキュー インコーポレイテッド | 皮膚細菌叢の解析に基づくカスタマイズしたスキンケア製品及びパーソナルケア製品 |
JP2017029133A (ja) * | 2015-07-21 | 2017-02-09 | TAK−Circulator株式会社 | 身体状態の評価方法、情報の提示方法、および身体状態を改善又は予防する物質のスクリーニング方法 |
JP2019208419A (ja) * | 2018-06-04 | 2019-12-12 | 日本メナード化粧品株式会社 | 赤ニキビを予測する方法 |
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- 2023-07-28 WO PCT/JP2023/027791 patent/WO2024070185A1/fr unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014095608A (ja) * | 2012-11-09 | 2014-05-22 | Nippon Menaade Keshohin Kk | 皮膚に常在するアクネ菌の菌数を予測する方法 |
JP2016528880A (ja) * | 2013-06-18 | 2016-09-23 | プロダームアイキュー インコーポレイテッド | 皮膚細菌叢の解析に基づくカスタマイズしたスキンケア製品及びパーソナルケア製品 |
JP2017029133A (ja) * | 2015-07-21 | 2017-02-09 | TAK−Circulator株式会社 | 身体状態の評価方法、情報の提示方法、および身体状態を改善又は予防する物質のスクリーニング方法 |
JP2019208419A (ja) * | 2018-06-04 | 2019-12-12 | 日本メナード化粧品株式会社 | 赤ニキビを予測する方法 |
Non-Patent Citations (1)
Title |
---|
MCLAUGHLIN JOSEPH, WATTERSON STEVEN, LAYTON ALISON M, BJOURSON ANTHONY J, BARNARD EMMA, MCDOWELL ANDREW: "Propionibacterium acnes and Acne Vulgaris: New Insights from the Integration of Population Genetic, Multi-Omic, Biochemical and Host-Microbe Studies", MICROORGANISMS (BASEL), MDPI AG, SWITZERLAND, 13 May 2019 (2019-05-13), Switzerland, pages 128, XP055904975, [retrieved on 20220324], DOI: 10.3390/microorganisms7050128 * |
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