CN106687130A - Use of eubacterium in the prevention and treatment for colorectal cancer related diseases - Google Patents
Use of eubacterium in the prevention and treatment for colorectal cancer related diseases Download PDFInfo
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- CN106687130A CN106687130A CN201480080834.6A CN201480080834A CN106687130A CN 106687130 A CN106687130 A CN 106687130A CN 201480080834 A CN201480080834 A CN 201480080834A CN 106687130 A CN106687130 A CN 106687130A
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- 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
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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
- C12N1/205—Bacterial isolates
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- 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
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- 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
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- 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
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- Health & Medical Sciences (AREA)
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- Wood Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
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- General Health & Medical Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The application of microorganisms, particular Eubacterium strains, in treatment and prevention of colorectal cancer-related diseases is disclosed. The composition comprising the Eubacterium strains is involved.
Description
Cross-Reference to Related Applications
Nothing
Field
The present invention relates to microbiology, in particular it relates to it is related to treat and prevent colorectal cancer in this application
The Eubacterium bacterial isolateses of disease, and further relate to the compositionss comprising Eubacterium antibacterial and its application.
Background
Colorectal cancer (CRC) is the 3rd modal cancer forms, and is of cancer related mortality in the Western countries
Two main causes (Schetter AJ, Harris CRC (2011) Alterations of microRNAs contribute to
colon carcinogenesis.Semin Oncol 38：734-742, is incorporated herein by).Many people are diagnosed trouble
There is CRC, and annual many patients die from the disease in the whole world.Although current strategy, including operation, radiotherapy and change
Treat, for CRC has a significant clinical value, but the recurrence of Post operation cancer and transfer hinder these therapeutic modalities into
Work(.
The intestinal chronic inflammatory occurred in inflammatory bowel (IBD) is induced along gastrointestinal Continuous Damage and enhanced mucosa
Permeability, plays an important role in the development of colorectal cancer (CRC).With familial adenomatous polyposises and Hereditary non-polyposis
Hereditary syndrome together, IBD is first three excessive risk condition (Xie J, Itzkowitz SH (2008) Cancer of CRC
in inf lammatory bowel disease.World J Gastroenterol 14：378-389, is incorporated by reference into
Herein).In ulcerative colitiss (UC) patient, one of two kinds of main clinical manifestations of IBD, develop CRC relative risk with
Degree (Eaden JA, Abrams KR, Mayberry JF (2001) the The risk of related to the persistent period of disease
colorectal cancer in ulcerative colitis：a meta-analysis.Gut 48：526-535, by drawing
With being expressly incorporated herein).In IBD patient, this risk is annual after 8-10 to increase 0.5-1.0% (Munkholm P (2003)
Reviewarticle：the incidence and prevalence of colorectal cancer in inf
lammatory bowel disease.Aliment Pharmacol Ther 18Suppl 2：1-5, is incorporated by reference into this
Text).
People's intestinal microbiota comprising about 100,000,000,000,000 microorganisms is tied up to by Absorption And Metabolism thing (such as vitamin and short chain
Fatty acid) maintain host health (in gastrointestinal tract and whole body) in play a crucial role (Moore WE, Holdeman LV (1974)
Human fecal flora：the normal flora of 20 Japanese-Hawaiians.Appl Microbiol
27：961-979, is incorporated herein by).Recent research have proved that, the specific bacterial strain of antibacterial is related to enteral stable state
Adjust, to neuro muscular activity delivering Regulate signal (the Shanahan F (2004) of epithelium, mucomembranous immune system and intestinal
Probiotics in inf lammatory bowel disease-therapeutic rationale and role.Adv
Drug Deliv Rev 56：809-818, is incorporated herein by).Additionally, some symbiosis of people's intestinal microorganism group and cause a disease
Biology is required in the pathogeny of IBD and CRC.Therefore, enterobacteria composition and local generation are manipulated by using probiotic bacteria
It is approach likely for CRC Results to thank to thing and be explored.Probiotic bacteria is microorganism feeding additive living, favorably
Ground affects the health of host.They depend on and specific external source bacterial strain are introduced in intestinal microbiota.For the research of CRC,
Inventor is analyzed in metagenomics field, and the data of the grand genome analysises of depth from CRC intestinal microorganism groups are presented.
Summary of the invention
The embodiment of the disclosure attempts at least to solve to a certain extent in problems of the prior art at least
One.
Following discovery of the present invention based on the present inventor：
The assessment of intestinal micropopulation and sign have become the Major research field of human diseasess, and the disease includes that knot is straight
Intestinal cancer (CRC), this is one of modal cause of death in all types of cancers.In order to the intestinal microorganism in CRC patient
Content is analyzed, present inventor has performed grand genome-full joint study (Megagenome-Wide Association
Study, MGWAS) scheme (Qin, J. et al. A metagenome-wide association study of gut
Microbiota in type 2diabetes.Nature 490,55-60 (2012), are incorporated herein by), which is based on
From the depth shotgun sequencing of the intestinal microbial DNA of 128 Chinese Individuals.The present inventor identifies 2 kinds of probiotic bacterias.Then originally
Inventor has separately verified the probiotic bacteria zoopery related to colitis and CRC.It is true that zooperal result demonstrates convex abdomen
Bacillus (Eubacterium ventriosum) and Eubacterium eligens (Eubacteriumeligens) effectively prevention and treatment knot
The ability of enteritis and colorectal cancer.
Brief description
Will be clear from and be easier with advantage in terms of by the following description for combining accompanying drawing, these and other of the disclosure
Understand, wherein：
Fig. 1 shows the P values association statistical distribution of all microbial genes in this research.The association point of CRC p values distribution
Analysis identifies the out-of-proportion excessive performance of the strong correlation label under relatively low P values, wherein most of genes are under null hypothesiss
Follow expected P Distribution values.This shows that significant label may represent true rather than false association.
The Eubacterium ventriosum ATCC 27560 that Fig. 2 gastric gives, Eubacterium ventriosum L2-12, Eubacterium ventriosum STAFF
1042, Eubacterium eligens ATCC 27750, Eubacterium eligens STAFF1020, Eubacterium eligens TSDC10.2-1.1 is respectively to DSS
Colitis C57BL/6J of induction lose weight at (A), the protective effect in terms of (B) disease activity index and (C) colon lengths.
Data are expressed as mean+/-standard error.Different asterisks (*) represents significant difference (* P<0.05, * * P<0.01, * * * p<
0.001)。
Used in Fig. 3 colons that the 15th day obtains after inducing colitis, ELISA (A) TNF-αs and (B) IL-10 are carried out
Quantitatively.Data are expressed as mean+/-standard error.Different asterisks (*) represents significant difference (* P<0.05, * * P<
0.01, * * * p<0.001)
Fig. 4 Eubacterium ventriosums ATCC 27560, Eubacterium ventriosum L2-12, Eubacterium ventriosum STAFF1042, fastidious true bar
Bacterium ATCC 27750, Eubacterium eligens STAFF 1020, Eubacterium eligens TSDC10.2-1.1 are respectively to (A) disease activity index
(B) therapeutical effect of colon's pathology.Different asterisks (*) represents significant difference (* P<0.05, * * P<0.01, * * * p<
0.001)
Fig. 5 Eubacterium ventriosums ATCC 27560, Eubacterium ventriosum L2-12, Eubacterium ventriosum STAFF1042, fastidious true bar
Bacterium ATCC 27750, Eubacterium eligens STAFF 1020, Eubacterium eligens TSDC10.2-1.1 regulate and control in BABL/C mices respectively
Colon gene expression (relative to beta-actin).Data are expressed as mean+/-standard error.Different asterisks (*) represents aobvious
Write difference (* P<0.05, * * P<0.01, * * * p<0.001).
Describe in detail
Terms used herein has the implication that the those of ordinary skill in field related to the present invention is generally understood that.Such as
" one kind ", " one " are not intended to only refer to singular entity with the term of " being somebody's turn to do ", but can be used for what is illustrated including specific embodiment
General category.Term herein is used to describe specific embodiments of the present invention, but their usage does not limit the present invention,
Unless summarized in the claims.
On the one hand, this application provides for preventing or treating the Eubacterium eligens of colitis and/or colorectal cancer or convex
Abdomen Eubacterium.On the other hand, this application provides Eubacterium eligens or Eubacterium ventriosum are used to prepare for preventing or treating knot
The purposes of the medicine of enteritis and/or colorectal cancer.On the other hand, this application provides for prevent or treat colitis and/or
The method of colorectal cancer, which includes to patient in need the Eubacterium eligens or Eubacterium ventriosum for applying effective dose.Another
Aspect, this application provides comprising Eubacterium eligens or Eubacterium ventriosum and its be used as medicine description test kit.This
Application additionally provides the pharmaceutical composition comprising Eubacterium eligens or Eubacterium ventriosum and pharmaceutically acceptable carrier.
Preferably, Eubacterium eligens are the bacterial strains selected from group consisting of：Eubacterium eligens ATCC 27750, it is fastidious
Eubacterium STAFF 1020 and Eubacterium eligens TSDC10.2-1.1.Preferably, the Eubacterium ventriosum is selected from the following group
Into group bacterial strain：Eubacterium ventriosum ATCC27560, Eubacterium ventriosum L2-12 and Eubacterium ventriosum STAFF1042.At one
In embodiment, Eubacterium eligens or convex abdomen are applied in the form of Eubacterium eligens living or Eubacterium ventriosum or its metabolite
Eubacterium.
The present invention is further illustrated in the following non-limiting examples.Unless otherwise stated, part and percentage ratio with
Weight meter, the number of degrees for degree Celsius.Although it will be obvious to those skilled in the art that indicating the preferred reality of the present invention
Scheme is applied, but these embodiments are only given by way of illustration, and reagent is all commercially available obtainable.
Embodiment
Embodiment 1. identifies the probiotic bacteria from 128 Chinese Individuals
1.1 sample collections and DNA extraction
In the case of informed consent, this prince hospital of Weir (Prince of Wales Hospital) collect from
The fecal specimens of 128 experimenters, including 74 colorectal cancer patients and 54 normal healthy controls (table 1).Include in order to qualified
This research, individual have to comply with following fecal specimens and collect standard：1) antibiotic or other drugs, no specific drink are not taken
Food (diabeticss, vegetarian etc.) and normal lifestyles (not having extra pressure) at least 3 months；2) any medical intervention
At least 3 months afterwards；3) no colorectal resection, or any kind of cancer, or the medical history of the inflammation or infectious disease of intestinal.
It is required that experimenter collected fecal specimens at home before colonoscopy in standardised container, and immediately sample is stored in
In domestic freezer case.Then frozen samples are transported to into Prince of Wales Hospital in insulation polystyrene foam container, are existed side by side
- 80 DEG C are stored in until using.
Fecal specimens are thawed on ice, and using QiagenQIAamp DNA Stool Mini Kit according to manufacturer
Description carry out DNA extraction.Extract is processed to eliminate RNA pollutions with the RNase without DNA enzymatic.Using NanoDrop light splitting
Photometer, Qubit exometers (determining test kit with Quant-iTTMdsDNA BR) and gel electrophoresiss determine amount of DNA.
The baseline characteristic of colorectal cancer case and control in 1 group of I of table.BMI：Body-mass index；eGFR：Epidermal growth factor
Sub- receptor；DM：Type 2 diabetes mellitus.
| Parameter | Matched group (n=54) | Case (n=74) |
| Age | 61.76 | 66.04 |
| Sex (M：F) | 33:21 | 48:26 |
| BMI | 23.47 | 23.9 |
| eGFR | 72.24 | 74.15 |
| DM (%) | 16 (29.6%) | 29 (39.2%) |
| Visible peristalsis visible intestinal peristalsis (Enterotype) (1：2：3) | 26:22:6 | 37:31:6 |
| Disease stage (1：2：3：4) | n.a. | 16:21:30:7 |
| Position (near-end：Distal end) | n.a. | 13:61 |
1.2DNA library constructions and sequencing
Description (2000 platforms of Illumina HiSeq) according to manufacturer carries out DNA library structure.The present inventor makes
Cluster generation, template hybridization, isothermal duplication, linearisation, closing and degeneration are carried out with workflow same as previously described, with
And hybridization (Qin, J. et al. A metagenome-wide association study of gut of sequencing primer
2 diabetes.Nature 490 of microbiota in type, 55-60 (2012), are incorporated herein by).
Inventor has double ends (PE) library of the Insert Fragment size for 350bp for each sample constructs one,
High-flux sequence is carried out subsequently to obtain about 30,000,000 PE readings of the length as 2x100bp.By filtering from initial data
Low quality reading with ' N' bases, adapter pollution and the pollution of people's source DNA, and by pruning the low quality for reading simultaneously
Terminal bases, extract high-quality reading.Generate 751,000,000 grand gene group number-readings (high-quality reading) (average every
Individuality has 5,860,000 readings, and table is 2).
1.3 readings map
High-quality reading is mapped to gene catalogue (table 2) to the disclosure set up by Europe and Chinese adult by the present inventor
Reference intestinal gene catalogue (Qin, J. et al. A metagenome-wide association study of gut
2 diabetes.Nature 490 of microbiota in type, 55-60 (2012), are incorporated herein by) (homogeneity
>=90%), based on this, the present inventor uses the same procedure of the T2D articles (paper) disclosed in Qin et al. (2012, ibid)
Derivative gene profile (gene profile).From reference gene catalogue (gene catalogue) such as Qin et al. (2012, ibid),
The present inventor has derived the individual genes of 2,110,489 (2.1M) at least 6 samples occurred in all 128 Hong Kong samples
Subset.
2. grand genomic data of table and the summary for being mapped to reference gene catalogue.4th row report is from Wilcoxon sums of ranks
The result of inspection.
| Parameter | Control | Case | P- values |
| Average original reading | 60162577 | 60496561 | 0.8082 |
| After deleting low quality reading | 59423292 (98.77%) | 59715967 (98.71%) | 0.831 |
| After deleting people's reading | 59380535±7378751 | 58112890±10324458 | 0.419 |
| Mapping rate | 66.82% | 66.27% | 0.252 |
1.4 affect the factorial analysiss of intestinal micropopulation gene profile
In order to ensure the robust of the gene content of 128 grand genomes compares (robust comparison), the present inventor
One group 2 is created, the individual genes of 110,489 (2.1M), which is present at least 6 experimenters, and uses this 2,100,000 genes
Produce 128 gene abundances and compose (abundance profile).Inventor is using displacement multivariate analysis of variance
(permutational multivariate analysis of variance) (PERMANOVA) inspection is different special to assess
Levy (include age, BMI, eGFR, TCHO, LDL, HDL, TG, sex, DM, CRC state, smoking state and position) to 2.1M bases
The impact of the gene profile of cause.The present inventor is analyzed using the method implemented in " vegan " bag in R, and by 10,
000 arrangement obtains arranged p value.The present inventor is also with Benjamini-Hochberg methods using in R
" p.adjust " correcting multiple check, to obtain the q values of each gene.
When inventor's covariant different to 13 kinds enters line replacement multivariate analysis of variance (PERMANOVA), only CRC states
It is significantly correlated with these gene profiles that (3) q=0.0028, table, is shown than the second optimal determiner BMI (body-mass index)
Higher association (q=0.15).Therefore, in as shown by data CRC patient microorganism group genomic constitution change.
PERMANOVA analysis of the table 3. using microbial gene spectrum.It is analyzed to test clinical parameter and colorectal cancer
(CRC) whether state has appreciable impact (q to intestinal micropopulation<0.05).BMI：Body-mass index；DM：Type 2 diabetes mellitus；
HDL：High density lipoprotein；TG：Triglyceride；eGFR：EGF-R ELISA；TCHO：T-CHOL；LDL；Low density lipoprotein
Albumen.
The 1.5 CRC related genes identified by MGWAS
1.5.1 the identification of colorectal cancer related gene.Present inventor has performed grand genome association analysis (MGWAS) is with mirror
The fixed contributive gene of genomic constitution to changing in CRC.In order to identify the association between grand genome spectrum and colorectal cancer,
Bilateral Wilcoxon rank tests used in the individual gene profiles of 2.1M (2,110,489).Inventor obtains 140,455 gene marks
Note thing, which is enriched with case or control, P<0.01 (Fig. 1).
1.5.2 estimate false positive rate (FDR).Replacement order P value method for removing, the present inventor are applied in previously research
" qvalue " method (J.D.Storey, R.Tibshirani, the Statistical significance for for proposing
genomewide studies.Proceedings of the National Academy of Sciences of the
United States of America 100,9440 (on August 5th, 2003), are incorporated herein by) estimating FDR.
In MGWAS, assumed statistical inspection is carried out to the big measure feature of 140,455 genes.False positive rate (FDR) is 11.03%.
1.6 data spectrums build
The sequencing reading of 128 micropopulations based on above-mentioned acquisition, inventor checked control and CRC related microorganisms
Taxonomic distinctness between group, to identify the micropopulation for causing ecological disturbance.For this purpose, the present inventor is using different from three kinds
Taxonomy spectrum (taxonomic profile) of method, because the supporting evidence from various methods will strengthen association.First,
Metagenomics reading is mapped to 4650 microbial genome in IMG data bases (edition 4 00) by the present inventor, and is estimated
The abundance of the microbial species (being expressed as IMG species (denoted IMG species)) being included in the data base.Secondly,
The present inventor estimates thing using general-purpose system development marker gene (universal phylogenetic marker gene)
The abundance of the molecule manipulation taxon (mOTU) of the level of kind.3rd, 140,455 genes that inventor will be identified by MGWAS
The grand genome linkage group (MLG) for representing the gene cluster from homologous genes group is organized into, as much as possible using IMG data bases
MLG is annotated in species level, based on these species annotation packet MLG, then estimates that the abundance of these species (is expressed as MLG things
Kind).
1.6.1 the species of IMG genomes annotate (Species annotation)
For each IMG genome, using the NCBI taxonomic history devices provided by IMG, inventor is turned using NCBI classification
Storage file (taxonomy dump file) identifies corresponding NCBI taxonomy classification on species and category level.Without corresponding
The genome of NCBI species names is kept its original I MG title, wherein most of unfiled.
1.6.2 gene profile
High-quality reading is mapped to gene catalogue to the disclosed ginseng set up by Europe and Chinese adult by the present inventor
Examine intestinal gene catalogue (Qin, J. et al. A metagenome-wide association study of gut microbiota
2 diabetes.Nature 490 of in type, 55-60 (2012), are incorporated herein by) (homogeneity >=90%), base
In this, the present inventor using with the derivative gene profile of the same procedure of the T2D articles disclosed in Qin et al. (2012, ibid).
1.6.3 mOTU is composed
Using default parameterss (S.Sanagawa et al., Metagenomic species profiling using
10,1196 (Dec, 2013), by drawing of universal phylogenetic marker genes. Nature methods
With being expressly incorporated herein) clean reading (the high-quality reading in embodiment 1) is compared with reference to (79268 sequences altogether) with mOTU.
Identify the mOTU of 549 species levels, including 307 annotated species and 242 mOTU for not having representative genome
Linkage group, which is estimated to be Firmicutes (Firmicutes) or Bacteroidetes (Bacteroidetes).
1.6.4 IMG species and IMG category are composed
Http is downloaded from from down：//ftp.jgi-psf.org IMG v400 reference databases (V.M.Markowitz et al.,
IMG：the Integrated Microbial Genomes database and comparative analysis
System. Nucleic acids research 40, D115 (2012) Jan, is incorporated herein by) extract antibacterial, ancient
Antibacterial and fungal sequence.Obtain altogether 522,093 sequence, and the block (chunk) of 7 equal sizes based on original document
Build SOAP reference keys (reference index).Using SOAP comparative device (R.Li et al., SOAP2：an improved
(2009) Aug 1, leads to ultrafast tool for short read alignment, Bioinformatics 25,1966
Cross and be incorporated herein by reference) 2.22 editions, using parameter " 600-v 8-c of-m 4-s, 32-r, 2-n, 100-x, 0.9-p 3 "
Clean reading is compared with reference.Then, cover software (coverage software) to calculate each genome using SOAP
Reading cover, use genome length standardization, and be further directed to the relative abundance of each individual sample and be standardized.Spectrum
It is based only upon the reading of unique mapping and generates.
The identification of 1.7 colorectal cancer relative species
Based on 140,455 colorectal cancer mark of correlation thing gene profiles of identification, the 2 types sugar before the present inventor's priority of use
Method (such as Qin et al. 2012, ibid) described in urine disease research builds colorectal cancer correlation MLG.All genes and IMG data
The reference gene group of storehouse v400 compares to obtain genomic level annotation.If>50% constitutive gene annotation arrives genome, then
MLG is assigned to into the genome, otherwise which is referred to as non-classified.Altogether 87 MLGs of the Select gene number more than 100 are used as knot
Rectal cancer correlation MLG.These MLG are grouped based on the species annotation of these genomes, to build MLG species.
In order to estimate the relative abundance of MLG species, inventor remove that 5% is minimum and 5% highest abundance gene after, estimation
The average abundance of the gene of MLG species.The phase of IMG species is estimated by the abundance of total IMG genomes for belonging to the species
To abundance.
These Analysis and Identification 30 IMG species significantly correlated with CRC states, 21 mOTU and 86 MLG species
(Wilcoxon rank tests, q<0.05；Referring to table 4,5).In all three method (Wilcoxon rank test-IMG：Q=
0.0414；mOTU：Q=0.012757；MLG：Q=5.446 × 10-4) in, Eubacterium ventriosum is as one man enriched in control microorganism
In group, and Eubacterium eligens (Wilcoxon rank test-IMG are enriched according to two methods：Q=0.069；MLG：Q=
0.00031).These results indicate that both species prevention and treatment CRC relevant diseases in as probiotic bacteria have it is very big
Ability.
On the other hand, Parvimonas micra (q<1.80x10-5), Peptostreptococcus stomatis (q<
1.80x10-5), Solobacterium moorei (q<0.004331) with Fusobacterium nucleatum (Fusobacterium
nucleatum)(q<0.004565) as one man it is enriched in CRC patient micropopulation in all three method.
P.stomatis (S.Pullalkar et al., Comparison of oral microbiota in tumors relevant with oral cancer
and non-tumor tissues of patients with oral squamous cell carcinoma.BMC
Microbiology 12,144 (2012), is incorporated herein by), S.moorei is relevant with bacteremia
(R.M.Pedersen, H.M.Holt, U.S.Justesen, Solobacterium moorei bacteremia：
Identification, antimicrobial susceptibility, and clinical
Characteristics.Journal of clinical microbiology 49,2766 (in July, 2011), by quoting
It is expressly incorporated herein).Have been observed that Fusobacterium nucleatum is significantly rich in CRC tumor samples using the nearest research that 16S rRNA are sequenced
Collection (M.Castellarin et al., Fusobacterium nucleatum infection is prevalent in human
Colorectal carcinoma.Genome research 22,299 (2012) Feb, is incorporated herein by), and
This antibacterial has been shown with viscosity (G.Bachrach, C.Ianculovici, R.Naor, E.I.Weiss, Fluorescence
based measurements of Fusobacterium nucleatum coaggregation and of
fusobacterial attachment to mammalian cells.FEMS microbiology letters 248,235
(Jul 15,2005) be incorporated herein by), invasive (Y.W.Han et al., Interactions between
periodontal bacteria and human oral epithelial cells：Fusobacterium nucleatum
Adheres to and invades epithelial cells.Infection and immunity 68,3140 (Jun,
2000), it is incorporated herein by), and proinflammatory disease (A.D.Kostic et al., Fusobacterium nucleatum
Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune
Microenvironment.Cell Host Microbe 14,207 (2013), are incorporated herein by) characteristic.These knots
Fruit confirms this association in the new colony with different heredity and culture origin.However, P.micra (obligate anaerobic is thin
Bacterium (obligate anaerobic bacterium), its can cause oral cavity infection such as Fusobacterium nucleatum (G.sundqvist,
Taxonomy, ecology, and pathogenicity of the root canal flora.Oral surgery, oral
Medicine, and oral pathology 78,822 (1994) Oct, is incorporated herein by) are in CRC related micro- life
The enrichment of the highly significant in thing is a kind of new discovery.P.micra participates in the etiology of periodontal disease (periodontis)
(B.H.Kremer et al., Peptostreptococcus micros smooth and rough genotypes in
Periodontitis and gingivitis.Journal of periodontology 71,209 (2 months 2000), pass through
Be incorporated herein by reference), and its produce wide scope proteolytic enzyme and use peptone and aminoacid as the energy
(D.A.Murdoch, H.N.Shah, Reclassification of Peptostreptococcus magnus (Prevot
1933)Holdeman and Moore 1972 as Finegoldia magna comb.Nov.and
Peptostreptococcus micros(Prevot 1933)Smith 1957 as
Micromonasmicroscomb.nov.Anaerobe 5,555 (10//, 1999), it is incorporated herein by).Known its life
Produce hydrogen sulfide (J.Carlsson, J.T.Larsen, M.B.Edlund, Peptostreptococcus micros has a
uniquely high capacity to form hydrogen sulfide from glutathione.Oral
Microbiology and immunology 8,42 (1993) Feb, is incorporated herein by), its promote tumour growth and
Propagation (C.Szabo et al., Tumor-derived hydrogen sulfide, the produced by of colon cancer cell
Cystathionine-beta-synthase, stimulates bioenergetics, cell proliferation, and
angiogenesis in colon cancer.Proceedings of the National Academy of Sciences
Of the United States of America 110,12474 (on July 23rd, 2013), are incorporated herein by).Need
Further to study to verify whether P.micra participates in the pathogenesis of CRC, or whether its enrichment is colon and/or rectum
The result of middle CRC associated changes.However, it may represent the chance of the non-invasive diagnostic biomarker of CRC.
Checking in 2. zoopery of embodiment
In order to verify the ability of probiotic bacteria, Eubacterium ventriosum and Eubacterium eligens in prevention and treatment CRC relevant diseases,
Present inventor has performed zoopery.
2.1 checkings in the zoopery related to colitis
2.1.1 method
The C57BL/6J mices of ten to ten two week old of the colitis research induced for DSS are prepared under the conditions of SPF.
After domestication, some animals arbitrarily obtain the drinking water containing 3.5-5%DSS (dextran sulfate sodium), continue 5 days, for colon
Scorching induction.Eubacterium ventriosum ATCC27560, Eubacterium ventriosum L2-12, Eubacterium ventriosum STAFF 1042, Eubacterium eligens
ATCC27750, Eubacterium eligens STAFF 1020, Eubacterium eligens TSDC10.2-1.1 (109-1010Cfu/ml is fresh daily
Prepare) bacterial suspension or medium after inducing colitis the 1st day to the 14th day by intragastric gavage daily respectively to little
Mus are applied.Without colitis and colitis Control group at gastric accepting medium (daily 500 μ l/50g.BW, every group of n=10).
C57BL/6J mices are purchased from southern china medical university Experimental Animal Center.Eubacterium ventriosum ATCC 27560 and choose
Eubacterium ATCC 27750 is picked purchased from American Type Culture Collection (ATCC).
Eubacterium ventriosum L2-12：Estelle Devillard, Freda M.McIntosh, Sylvia H.Duncan and
R.John Wallace (in March, 2007).Metabolism of Linoleic Acid by Human Gut Bacteria:
Different Routes for Biosynthesis of Conjugated Linoleic Acid.Journal of
Bacteriology 189(6)：2566-2570.
Eubacterium ventriosum STAFF 1042, Eubacterium eligens STAFF 1020：Kageyama, A et al.
Rapiddetection of human fecal Eubacterium species and related genera by
Nested PCR method, Microbiology and Immunology (2001) 45 (4)：315-318.
Eubacterium eligens TSDC10.2-1.1 is purchased from University of Washington (U.S.) http in St. Louis://
www.genomesonline.org/projectsId=47012.
Mice is observed daily and records clinical measures.Before DSS administrations and after intragastric gavage weekly, to experiencing DSS
Body weight and disease activity index (table 6) (Alex P, Zachos NC, Nguyen T, Gonzales L, the Chen of the mice of stimulation
TE, Conklin, LS et al. 2009Distinct cytokine patterns identified from
multiplexprofiles of murine DSS and TNBS-induced colitis.Inflamm Bowel Dis；15
(3)：341-52, is incorporated herein by), ((such as perianal pollution, rectum go out a kind of clinical sign of reflection disease
Blood and diarrhoea etc.) comprehensive score) be estimated, after inducing colitis the 15th day monitoring inflammation, now by cervical dislocation
Put to death mice.
6 clinical score standard of table
Colon is taken out, fat-free and mesentery is cut off, it is careful to open, and cleaned with PBS (phosphate buffered saline (PBS)).Measurement
Colon lengths.Traumatic Colon and inflammation are assessed in the case of unwitting according to Wallace standards.Colon is also collected in into liquid nitrogen
In and be stored in -80 DEG C for ELISA (enzyme-linked immunosorbent assay) check.
2.1.2 result
2.1.2.1 in mice DSS induction colitis the order of severity respectively by Eubacterium ventriosum ATCC 27560, convex abdomen
Eubacterium L2-12, Eubacterium ventriosum STAFF 1042, Eubacterium eligens ATCC 27750, Eubacterium eligens STAFF 1020, choose
Pick Eubacterium TSDC10.2-1.1 reductions.
The present inventor is by testing Eubacterium eligens ATCC 27750, STAFF 1020, TSDC10.2-1.1 and convex respectively
Abdomen Eubacterium L2-12, STAFF 1042, ATCC 27560 recovers the ability of the acute colitis induced by DSS, probes in vivo
Anti-inflammatory effect.After DSS process, serious acute inflammation is observed in colitis Control group, and is receiving aseptic culture
Significant protective effect is not observed in the mice of medium.By contrast, 6 kinds of Eubacterium bacterial strains living distinguish daily gastric
Administration results in the notable mitigation of colitis, loses weight (table 7, Fig. 2A) with what is reduced, and the 7th after intragastric gavage
It and the 14th day reduce the disease activity index related to colitis (data spectrum of the 7th day is similar with the data spectrum of the 14th day, this
Place is not shown).And compared with media processes group, segmental colonic length is standardized (table 8, Fig. 2 B, 2C).In intragastric gavage
During beginning, body weight and disease activity index do not have difference.Data are expressed as mean+/-standard error.
Data (the W0 of 7 body weight of table：DSS before processing body weight；W1：The body weight of the 7th day after intragastric gavage)
* ATCC 27560 represents Eubacterium ventriosum ATCC 27560；L2-12 represents Eubacterium ventriosum L2-12, STAFF
1042 represent Eubacterium ventriosum STAFF 1042, and ATCC 27750 represents Eubacterium eligens ATCC 27750,1020 generations of STAFF
Table Eubacterium eligens STAFF 1020, TSDC10.2-1.1 represents Eubacterium eligens TSDC10.2-1.1.
The data of the clinical measurement related to colitis of table 8
2.1.2.2 Eubacterium ventriosum ATCC 27560, Eubacterium ventriosum L2-12, Eubacterium ventriosum STAFF 1042, fastidious
Eubacterium ATCC 27750, Eubacterium eligens STAFF 1020, Eubacterium eligens TSDC10.2-1.1 adjust colitis respectively
Expression
By proinflammatory TNF-α (tumor necrosis factor α) cytokine of the quantitative colons of ELISA and anti-inflammatory IL-10 (leukocyte
Interleukin -10).Compared with without colitis Control group, TNF-α level increases, and IL-10 levels almost do not have in colitis mice
Change.After being processed with the suspension of Eubacterium eligens ATCC 27750, (8) Fig. 3 A, table are substantially less than colitis for the secretion of TNF-α
Matched group and medium group.Meanwhile, IL-10 secretions are induced in the colon of the mice processed with ATCC 27750, and (Fig. 3 B, table is 8).
With Eubacterium ventriosum ATCC 27560, Eubacterium ventriosum L2-12, Eubacterium ventriosum STAFF 1042, Eubacterium eligens STAFF
1020 and Eubacterium eligens TSDC10.2-1.1 (Fig. 3, it was observed that similar phenomenon in the C57Bl/6J mices that 8) table is administered.
Checking in 2.2 zooperies related to colorectal cancer
2.2.1 method
BABL/c mices are oxidized azomethane (AOM, 10mg/kg) in 10 week old to be stimulated, then at the 2nd week, the 5th week
Started with the 8th week with the drinking water treatment for containing 2.0% dextran sulfate sodium (DSS) 7 days, it is straight with the knot that inducing colitis are related
Intestinal cancer (CRC).Then Eubacterium ventriosum ATCC 27560, L2-12, STAFF 1042 were used respectively from the 9th week of research, and it is fastidious
Eubacterium ATCC 27750, STAFF 1020, TSDC10.2-1.1 (109-1010cfu/ml, daily fresh preparation) or control are situated between
Matter processes mice, until putting to death (daily 0.1ml/50g.BW, every group n=15) by cervical dislocation at the 11st week.BABL/c is little
Mus are purchased from southern china medical university Experimental Animal Center.
Calculate disease activity index as previously mentioned, its be before intragastric gavage and intragastric gavage after weekly, to experience
The mice that AOM+DSS stimulates is estimated.
For histopathological examination, after postmortem, section of colon is fixed in the neutral formalin of 10% buffering, subsequently
It is embedded in paraffin, then cuts into slices (6 μm) and dyeed with H＆E (h and E).In Olympus microscope (lympus
America Inc., Dulles, VA) middle inspection histological slides.Specimen through ignorant histological examination, and in adenoma and gland
Score in terms of cancer 1-4.
For RNA separates the real-time polymerase chain reaction with cytokine, Qiagen is used according to the description of manufacturer
RNA separating kits (Qiagen) separate the tTotalRNA from colon, then using iScript cDNA synthetic agent box
(Bio-Rad, Hercules, CA) uses it for producing cDNA templates, and carries out real-time RT-PCR as previously mentioned
(Bassaganya-Riera J, Reynolds K, Martino-Catt S, Cui Y, Hennighausen L, et al.
(2004), Activation of PPAR gamma and delta by conjugated linoleic acid
mediates protection from experimental inflammatory bowel disease.Gastroen-
terology 127:777-791, be incorporated herein by).CD36 and PPAR γ (peroxidating is assessed by real-time quantitative PCR
Thing enzyme body proliferation activated receptor γ) mRNA expression.
2.2.2 result
2.2.2.1 continuing to give within 2 weeks Eubacterium ventriosum L2-12 daily or Eubacterium ventriosum STAFF 1042 or convex abdomens are true
Bacillus ATCC 27560 or Eubacterium eligens STAFF 1020 or Eubacterium eligens TSDC10.2-1.1 or Eubacterium eligens ATCC
After 27750, disease activity index is substantially less than CRC matched groups (table 9), and straight in the knot of inflammation driving before intragastric gavage
Difference is not shown in intestinal cancer model (data not here it is shown that).And have detected 6 kinds of Eubacterium bacterial strains and process right respectively
Experiment azoxymethane induction colorectal cancer the pathological impact of colon, and it is all these process and compare
Comparing reduces adenoma and adenocarcinoma and forms that (Fig. 4, table is 9).
2.2.2.2 Eubacterium ventriosum L2-12 or Eubacterium ventriosum STAFF1042 or Eubacterium ventriosum ATCC 27560 or choose
Pick Eubacterium STAFF1020 or Eubacterium eligens TSDC10.2-1.1 or Eubacterium eligens ATCC27750 adjusts colitis respectively
Disease and the expression of carcinogenic label.
The mice stimulated with azoxymethane and DSS was euthanized in the lotus knurl stage of disease.Use Eubacterium eligens
ATCC 27750 or Eubacterium eligens STAFF 1020 or Eubacterium eligens TSDC10.2-1.1 or Eubacterium ventriosum L2-12 or convex
Those mices that abdomen Eubacterium STAFF 1042 or Eubacterium ventriosum ATCC 27560 is processed are compared with the matched group of media processes
Show that the mRNA expression of the CD36 and PPAR γ in colon increases that (Fig. 5, table is 9).
The data of the clinical measurement related to CRC of table 9
| Group | Disease activity index | CD36 | PPAR-γ | Adenoma and adenocarcinoma |
| Health | 0 | 0.92±0.25 | 38.22±7.06 | 0 |
| CRC is compareed | 10.7±3.0 | 0.40±0.34 | 29.43±8.14 | 2.3±0.8 |
| ATCC 27750 | 8.2±2.5 | 0.67±0.30 | 32.17±8.03 | 1.2±0.3 |
| STAFF 1020 | 8.9±2.2 | 0.72±0.37 | 34.82±5.79 | 1.7±0.5 |
| TSDC10.2-1.1 | 7.9±3.0 | 0.65±0.29 | 35.67±3.96 | 1.5±0.7 |
| ATCC 27560 | 7.4±2.1 | 0.75±0.26 | 34.25±5.23 | 1.6±0.5 |
| L2-12 | 9.1±1.8 | 0.71±0.39 | 36.11±7.40 | 1.4±1.1 |
| STAFF 1042 | 8.8±2.4 | 0.69±0.40 | 35.93±6.67 | 1.7±0.6 |
In a word, result of this study demonstrate that Eubacterium ventriosum L2-12 or the true bar of Eubacterium ventriosum STAFF1042 or convex abdomens
Bacterium ATCC 27560 or Eubacterium eligens STAFF 1020 or Eubacterium eligens TSDC10.2-1.1 or Eubacterium eligens ATCC
27750 abilities for improving both colitis and colorectal cancer.
While there has been shown and described that illustrative embodiment, it should be appreciated to those skilled in the art that above-mentioned reality
The scheme of applying is not construed to limit the disclosure, and in the case of the spirit without departing from the disclosure, principle and scope, can be with
Embodiment is changed, substitutions and modifications.
Claims (13)
1. it is used for preventing or treating the Eubacterium ventriosum of colitis and/or colorectal cancer.
2. the Eubacterium ventriosum of purposes according to claim 1 is used for, wherein the Eubacterium ventriosum is selected from following
The bacterial strain of the group of composition：Eubacterium ventriosum ATCC 27560, Eubacterium ventriosum STAFF 1042 and Eubacterium ventriosum L2-12.
3. for the Eubacterium ventriosum of the purposes according to claim 1 or claim 2, wherein the Eubacterium ventriosum with
The form of Eubacterium ventriosum living or its metabolite is applied.
4. the purposes that Eubacterium ventriosum is used in the medicine for preventing or treating colitis and/or colorectal cancer in preparation.
5. purposes according to claim 4, wherein the Eubacterium ventriosum is the bacterial strain selected from group consisting of：Convex abdomen is true
Bacillus ATCC 27560, Eubacterium ventriosum STAFF 1042 and Eubacterium ventriosum L2-12.
6. the purposes according to claim 4 or claim 5, wherein the Eubacterium ventriosum with Eubacterium ventriosum living or
The form of its metabolite is applied.
7. a kind of method for preventing or treating colitis and/or colorectal cancer, applies effective including to patient in need
The Eubacterium ventriosum of amount.
8. method according to claim 7, wherein the Eubacterium ventriosum is the bacterial strain selected from group consisting of：It is convex
Abdomen Eubacterium ATCC 27560, Eubacterium ventriosum STAFF 1042 and Eubacterium ventriosum L2-12.
9. the method for claim 7 or claim 8, wherein the Eubacterium ventriosum is with Eubacterium ventriosum living or its metabolite
Form apply.
10. it is a kind of comprising Eubacterium ventriosum and its description as medicine test kit.
The test kit of 11. claim 10, wherein the Eubacterium ventriosum is the bacterial strain selected from group consisting of：Convex abdomen is true
Bacillus ATCC 27560, Eubacterium ventriosum STAFF 1042 and Eubacterium ventriosum L2-12.
A kind of 12. pharmaceutical compositions, which includes Eubacterium ventriosum and pharmaceutically acceptable carrier.
The pharmaceutical composition of 13. claim 12, wherein the Eubacterium ventriosum is the bacterial strain selected from group consisting of：It is convex
Abdomen Eubacterium ATCC 27560, Eubacterium ventriosum STAFF 1042 and Eubacterium ventriosum L2-12.
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| EP3240554B1 (en) | 2015-06-15 | 2019-07-31 | 4D Pharma Research Limited | Blautia stercosis and wexlerae for use in treating inflammatory and autoimmune diseases |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101590081A (en) * | 2008-05-28 | 2009-12-02 | 青岛东海药业有限公司 | Eubacterium ventriosum and Eubacterium biforme preparation and application thereof |
| WO2012142605A1 (en) * | 2011-04-15 | 2012-10-18 | Samaritan Health Services | Rapid recolonization deployment agent |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1333564C (en) * | 1988-08-02 | 1994-12-20 | Thomas Julius Borody | Treatment of gastro-intestinal disorders |
| CN101744239A (en) * | 2008-12-01 | 2010-06-23 | 青岛东海药业有限公司 | Application of dietary fibers in the preparation of pharmaceutical preparations for preventing and curing excrement smelling or excrement smelling poisoning syndrome |
| EP2756071B1 (en) * | 2011-09-14 | 2017-12-20 | University Of Guelph | Media supplements and methods to culture human gastrointestinal anaerobic microorganisms |
-
2014
- 2014-08-05 WO PCT/CN2014/083689 patent/WO2016019506A1/en active Application Filing
- 2014-08-05 CN CN201480080834.6A patent/CN106687130B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101590081A (en) * | 2008-05-28 | 2009-12-02 | 青岛东海药业有限公司 | Eubacterium ventriosum and Eubacterium biforme preparation and application thereof |
| WO2012142605A1 (en) * | 2011-04-15 | 2012-10-18 | Samaritan Health Services | Rapid recolonization deployment agent |
Non-Patent Citations (2)
| Title |
|---|
| W.E.C.MOORE ET AL.: "Discussion of Current Bacteriological Investigations of the Relationships between Intestinal Flora,Diet,and Colon Cancer", 《CANCER RESEARCH》 * |
| W.E.C.MOORE ET AL.: "Intestinal Floras of Populations That Have a High Risk of Colon Cancer", 《APPLIED AND ENVIRONMENTAL MICROBIOLOGY》 * |
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