CN112852981A - Intestinal microbial marker of abdominal aortic aneurysm and application thereof - Google Patents
Intestinal microbial marker of abdominal aortic aneurysm and application thereof Download PDFInfo
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Abstract
The invention relates to an intestinal microbial marker of abdominal aortic aneurysm and application thereof. The invention determines 30 intestinal microbial markers of abdominal aortic aneurysm based on a classifier modeling evaluation and verification method of intestinal microbial abundance, wherein 25 intestinal microbial markers are up-regulated and 5 intestinal microbial markers are down-regulated, and high-risk groups of abdominal aortic aneurysm can be effectively screened or early patients can be found according to the intestinal microbial markers of abdominal aortic aneurysm, so that the abdominal aortic aneurysm can be prevented from further expanding and the rupture risk can be reduced as soon as possible, and the treatment effect of the abdominal aortic aneurysm can be monitored. Meanwhile, the intestinal microbial marker can be used for preparing a diagnostic kit and a therapeutic drug. The invention overcomes the defects that the existing abdominal aortic aneurysm diagnosis can not realize early screening and can not predict the onset and development trend of the abdominal aortic aneurysm, and the like, and can help disease pathological typing, medicine action target point research, accurate medication, pathogenesis research and the like.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and mainly relates to an intestinal microbial marker of abdominal aortic aneurysm and application thereof.
Background
Abdominal aortic aneurysms are the most common aneurysms and are a serious health-threatening circulatory system disease. Abdominal Aortic Aneurysm (AAA) refers to abnormal or localized expansion of a section of the abdominal aorta, with a transverse diameter > 3cm or more than 50% of the normal abdominal aorta diameter, and finally causes a high-risk disease that the vessel wall cannot bear the impact of blood flow and breaks. The incidence of abdominal aortic aneurysm is on the increasing trend year by year, most of the cases occur above 50 years old, especially in men and patients with family history of the disease, and other risk factors include smoking, hypertension, coronary heart disease, high cholesterol, peripheral arterial disease, high homocysteine level and the like. The pathogenesis of the disease comprises: the action of matrix metalloproteinases leads to the destruction of the extracellular matrix; inflammation and oxidative stress; vascular smooth muscle cell apoptosis; abnormalities in the innate immune system include Toll-like receptor upregulation, chemokine receptor activation, and complement deposition. In addition, studies have been made in recent years to show that hyperhomocysteinemia and metabolic intermediates of tryptophan are involved in the progression of abdominal aortic aneurysms.
Abdominal aortic aneurysms are highly fatal cardiovascular diseases associated with hypertension and no effective drug therapy is currently available. Before rupture, abdominal aortic aneurysms usually have no obvious symptoms, but structural pathological changes of weak abdominal aortic walls and hypotonia exist, and the rupture of the aneurysm is easily induced when defecation, anger and heavy object carrying are performed by force. The fear of the method is that once a tumor body is broken, massive bleeding is caused, so that a patient mostly dies from hemorrhagic shock and quickly dies, and therefore, the name of 'untimely bomb' in a human body is often that the human body is not ready to suddenly 'explode'. In particular, the mortality rate from acute bleeding after rupture is higher in elderly patients with other diseases, and once ruptured, the mortality rate is 85% to 90%. Today with such advanced medical treatments, the first problem in the medical field is faced with the highly insidious but extremely harmful disease. Therefore, early diagnosis and early treatment are found, and the prevention of the aggravation and rupture of the abdominal aortic aneurysm is urgent.
Currently, the diagnosis of abdominal aortic aneurysms in the clinic relies mainly on abdominal B-ultrasound and CTA. The ultrasonic examination of the abdominal aorta is more difficult than the lower limb veins and the carotid arteries, because the abdominal aorta is shielded by the foregut tube and other visceral organs, the ultrasonic examination image is unclear, the diagnosis is difficult, and especially the early-stage aneurysm with the diameter of 3-4cm accounts for less than 10% of the abdominal aortic aneurysm found by screening. CTA (CT angiography) is the gold standard for diagnosing abdominal aortic aneurysms. But has strict contraindications, and is forbidden for patients with iodine contrast agent allergy, liver and kidney insufficiency and serious arrhythmia. Moreover, CTA is associated with large doses of ionizing radiation and may result in a significant increase in the risk of developing cancer. Most physical examination units do not perform specific physical examination on the abdominal aorta at present, so that the abdominal aortic aneurysm is difficult to find.
In recent years, scientists have found through research that the intestinal microbiota of the body is closely related to various diseases of human beings. However, the relationship between intestinal microbiota and abdominal aortic aneurysm is not reported at present, and no reliable intestinal microbiota marker exists in abdominal aortic aneurysm. Furthermore, the current diagnostic criteria do not allow early prediction of the onset of abdominal aortic aneurysms.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the intestinal microbial marker of the abdominal aortic aneurysm and the application thereof, and the intestinal microbial marker of the abdominal aortic aneurysm can effectively screen high-risk groups of the abdominal aortic aneurysm at early stage or discover early-stage patients so as to prevent the further expansion of the abdominal aortic aneurysm and reduce the rupture risk as early as possible, and can help disease pathological typing, medicine action target point research, accurate medication, pathogenesis research and the like.
The technical scheme of the invention is as follows:
the present invention provides an intestinal microbial marker of abdominal aortic aneurysm, comprising 30 microorganisms,
wherein, the intestinal microorganism markers of the abdominal aortic aneurysm patient are as follows:
(1)Roseitalea_porphyridii；
(2)Streptomyces_peucetius；
(3)Pseudonocardia_autotrophica；
(4)Agrobacterium_fabrum；
(5)Enterobacter_cloacae_complex_sp._FDA-CDC-AR_0132；
(6)Gordonibacter_pamelaeae；
(7)Neokomagataea_sp._Ha5；
(8)Enterobacter_ludwigii；
(9)Simian_immunodeficiency_virus；
(10)Burkholderia_plantarii；
(11)Burkholderia_multivorans；
(12)Saimiriine_alphaherpesvirus_1；
(13)Actinosynnema_pretiosum；
(14)Georgenia_sp._ZLJ0423；
(15)Amycolatopsis_orientalis；
(16)Acetobacter_persici；
(17)Ruthenibacterium_lactatiformans；
(18)Synechococcus_sp._CB0101；
(19)Xanthomonas_vasicola；
(20)Geobacter_anodireducens；
(21)Cupriavidus_metallidurans；
(22)Adoxophyes_honmai_entomopoxvirus；
(23)Actinomadura_sp._WMMA1423；
(24)Legionella_oakridgensis；
(25)Klebsiella_quasipneumoniae；
the intestinal microbial markers decreased in patients with abdominal aortic aneurysm were as follows:
(1)Haemophilus_parainfluenzae；
(2)Candidatus_Rhodoluna_planktonica；
(3)Vibrio_phage_PWH3a-P1；
(4)Roseburia_intestinalis；
(5)Pseudomonas_asplenii。
in the invention, the method for determining the intestinal microbial markers of the abdominal aortic aneurysm is a classifier modeling evaluation and verification method based on the abundance of intestinal microbiota, and comprises the following steps:
I. obtaining fecal samples of 31 healthy people and 33 abdominal aortic aneurysm patients, extracting DNA for metagenomic sequencing, wherein the method is PE150, performing quality control on original data by using kneaddata to remove a host, cutting reads with average base mass less than 20, performing species annotation by using kraken2, and calculating the relative abundance of each species in each sample;
II. Numbering healthy people and abdominal aortic aneurysm patients, generating 30 random numbers by using an R language, taking people corresponding to corresponding numbers as a training set, taking the rest 34 healthy people and abdominal aortic aneurysm patients as a test set, training the training set by using a machine learning random forest model, classifying and predicting the quality of a preliminary evaluation model by the test set, optimizing parameters of the random forest model to retrain if the prediction Accuracy is lower than 75%, until the prediction Accuracy is higher than 75%, verifying and checking the corresponding feature number when the lowest error rate is checked by cross-folding cross validation, and selecting an intestinal tract microbial marker according to the cross-folding cross validation result and the importance score of Mean precision reduction (Mean increment Accuracy), wherein the error rate is the lowest when the microbial number is 32, and the intestinal tract microbial marker is the best model;
and III, selecting the first 30 intestinal microorganisms which are arranged in a descending order according to Mean precision descent (Mean increment Accuracy) as intestinal microorganism markers of the abdominal aortic aneurysm, and dividing the intestinal microorganism markers into an intestinal microorganism marker increasing group (AAA increase) and an intestinal microorganism marker decreasing group (AAA Decrease).
The invention provides application of the intestinal microbial marker of the abdominal aortic aneurysm as a prediction factor in early screening of the abdominal aortic aneurysm.
The invention carries out gene sequencing on the intestinal microbiota separated from a detection object, compares the abundance value of the obtained intestinal microbial marker of the abdominal aortic aneurysm with a preset value, and carries out early screening on the abdominal aortic aneurysm.
The invention provides application of the intestinal microbial markers of the abdominal aortic aneurysm in preparation of a tool for early screening or prediction of the abdominal aortic aneurysm.
Preferably, the tool for early screening or prediction of abdominal aortic aneurysm comprises an early screening or pre-testing kit for abdominal aortic aneurysm.
Further preferably, the early screening or pre-testing kit for abdominal aortic aneurysm comprises a detection reagent for intestinal microbial markers of the abdominal aortic aneurysm.
Further preferably, the detection reagent comprises a primer specific to the intestinal microbial marker of the abdominal aortic aneurysm.
The kit can be used for detecting the abundance of intestinal microbial markers of the abdominal aortic aneurysm, so that the obtained abundance value can be compared with a preset value, the early screening or prediction of the abdominal aortic aneurysm of a detection object can be carried out, or the treatment effect of a patient with the abdominal aortic aneurysm can be monitored.
The invention provides application of the intestinal microbial marker of the abdominal aortic aneurysm in preparation of a medicine for treating the abdominal aortic aneurysm.
According to the invention, the application is preferably to prepare or screen the medicament for treating the abdominal aortic aneurysm by taking the intestinal microbial marker of the abdominal aortic aneurysm as a target.
The present invention can utilize the effect of a candidate drug on the intestinal biomarkers of abdominal aortic aneurysm of the present invention before and after use to determine whether the candidate drug can be used to treat or prevent abdominal aortic aneurysm.
Preferably, according to the invention, the drug acts on the intestinal microbial marker of the abdominal aortic aneurysm as a target.
The invention provides application of the intestinal microbial marker of the abdominal aortic aneurysm in predicting individual treatment effect of patients with the abdominal aortic aneurysm.
The invention has the following beneficial effects:
the invention determines 30 intestinal microbial markers of abdominal aortic aneurysm based on a classifier modeling evaluation and verification method of intestinal microbiota abundance, wherein 25 intestinal microbial markers are up-regulated and 5 intestinal microbial markers are down-regulated, and high-risk groups of abdominal aortic aneurysm can be effectively screened or early patients can be found according to the intestinal microbial markers of abdominal aortic aneurysm, so that the abdominal aortic aneurysm can be prevented from further expanding and the rupture risk can be reduced as early as possible, and the treatment effect of the abdominal aortic aneurysm can be monitored. Meanwhile, the intestinal microbial marker can be used for preparing a diagnostic kit and a therapeutic drug. The invention overcomes the defects that the existing abdominal aortic aneurysm diagnosis can not realize early screening and can not predict the onset and development trend of the abdominal aortic aneurysm, can help disease pathological typing, medicine action target point research, accurate medication, pathogenesis research and the like, and provides a new treatment scheme.
Drawings
FIG. 1 is a flow chart of a method for determining gut microbial markers based on classifier modeling evaluation verification of gut microbiota abundance;
FIG. 2 is a shock chart of the species composition at the level of the intestinal microbiota in the abdominal aortic aneurysm patient group and in the healthy human group; wherein C is a healthy human group and P is an abdominal aortic aneurysm patient group; the right side is the latin name of the level of intestinal microbiota in the healthy population group and in the abdominal aortic aneurysm patient group; specifically, Archaea is Archaea, bacillia is Bacteria, Eukaryota is eukaryote, and virues are Viruses;
FIG. 3 is a plot of intestinal microbial species levels versus PCoA between a healthy human group and a patient group with abdominal aortic aneurysm;
FIG. 4 is a graph of the results of a random forest model using another data set (test set) to verify the results of predictions for (a) a healthy population group and (b) an abdominal aortic aneurysm patient group;
FIG. 5 shows cross-validation results of ten folds and results of 30 gut flora biomarkers determined from random forests; in the figure, Actinobacteria: actinomycete phyla; cyanobacteria: cyanobacteria phylum; firmicutes: firmicutes; proteobacteria: a proteobacteria; and (4) Virus: a virus; on the left side of the figure are the Latin names for the levels of 30 different microbial species screened in example 1; the small graph in the graph is a ten-fold cross validation result;
FIG. 6 is a graph of interclass distribution of the abdominal aortic aneurysm enriched intestinal microbial index (AAA incrased microbial index) and the abdominal aortic aneurysm reduced intestinal microbial index (AAA degrased microbial index); wherein (a) is a group distribution violin graph of abdominal aortic aneurysm enriching intestinal microorganism indexes, (b) is a group distribution violin graph of abdominal aortic aneurysm reducing intestinal microorganism indexes, # indicates that wilcoxon rank sum test P is less than 0.05;
FIG. 7 is a graph of the Abdominal aortic aneurysm enriched intestinal microbial index (AAA secreted microbial index) and Abdominal aortic aneurysm reduced intestinal microbial index (AAA secreted microbial index) for evaluation of the receiver operating characteristic Curve (ROC) and area under the Curve (AUC) in the test set;
FIG. 8 is a diagram of a violin with inter-set distribution of diastolic, systolic, cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, homocysteine, glucose, uric acid indicators; wherein SBP is diastolic pressure, DBP is systolic pressure, TC is serum total cholesterol, TG is serum triglyceride, HDL is high density lipoprotein, LDL is low density lipoprotein, HCY is homocysteine, glucose is glucose, UA is uric acid, # indicates wilcoxon rank sum test P < 0.05;
FIG. 9 is a graph of systolic blood pressure, diastolic blood pressure, cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, homocysteine, uric acid, and glucose index (AUC) estimates of the operating curve (ROC) and the area under the curve (AUC) of subjects in the test set for the abdominal aortic aneurysm patient group and the healthy human group; wherein SBP is diastolic pressure, DBP is systolic pressure, TC is serum total cholesterol, TG is serum triglyceride, HDL is high density lipoprotein, LDL is low density lipoprotein, HCY is homocysteine, glucose is glucose, and UA is uric acid.
Detailed Description
The technical solution of the present invention will be described in detail below with reference to specific examples.
A process for determining intestinal microbial markers by a classifier modeling evaluation and verification method based on intestinal microbiota abundance is shown in figure 1, and comprises the steps of firstly obtaining fecal samples and clinical index indexes of healthy people and abdominal aortic aneurysm patients, then carrying out macro-genome sequencing to obtain species composition, establishing a random forest model, optimizing model parameters and carrying out training, predicting by adopting another data set, evaluating the quality of the model, determining the number of the intestinal microbial markers and representative intestinal microbial markers according to species contribution and ten-fold cross validation after the model is established, calculating the intestinal microbial marker indexes, taking each index as a variable to serve as a working characteristic curve of a subject, calculating the area under the curve, and determining the accuracy of the intestinal microbial markers.
Example 1
The method for determining the intestinal microbial markers of the abdominal aortic aneurysm based on the classifier modeling evaluation verification method of the intestinal microbiota abundance comprises the following steps:
1. determination of the subject
Exclusion criteria for the abdominal aortic aneurysm patient group and healthy person group were:
(1) those suffering from the following: immune system diseases (SLE, arthritis, etc.), tumor diseases, liver cirrhosis, hypothyroidism, hyperthyroidism, peripheral vascular diseases, acute infectious diseases;
(2) the inflammation markers such as antibiotics or recent infection, leucocyte, neutrophil granulocytes, CRP and the like are obviously increased after being taken within two weeks;
(3) other medicines are taken in large quantities in the last month.
The information of the abdominal aortic aneurysm patient group and the healthy person group is shown in table 1.
TABLE 1 clinical data information of the study subjects
Note: and NS: p is more than 0.05, and no significant difference exists; # #: p is less than 0.01, and the difference is obvious.
2. Feces collection and preservation
Fresh, middle and later stage fecal samples were collected from abdominal aortic aneurysm patient groups and healthy groups in one tube and immediately frozen in a-80 ℃ freezer.
3. Extraction of intestinal microbial genome DNA
(1) Weighing 25-30mg of excrement, disinfecting a spoon between samples by using alcohol, storing the samples by using an enzyme eptube, and marking;
(2) adding 2 × CTAB preheated in 65 deg.C water bath, 300 μ L/sample, oscillating for 10s, and heating with 95 deg.C metal bath for 8 min;
(3) adding 300 μ L of phenol-chloroform (volume ratio of saturated phenol, chloroform and isoamylol is 25:24:1), shaking uniformly, 1000g/min, centrifuging for 5 min;
(4) the supernatant was transferred to a new 1.5mL ep tube and 3 volumes (600. mu.L) of a sol solution (B2 solution) were added using B518131 kit (sangon);
(5) adding 800 μ L of the liquid into a separation column in the kit, standing for 2min, 12000g/min, and centrifuging for 1 min;
(6) discarding the liquid, adding 400 μ L of washing solution into the separation column, standing for 2min, 12000g/min, and centrifuging for 1 min;
(7) repeating the step (6) once;
(8) abandoning the waste liquid in the recovery tube, emptying the tube at 12000g/min, and centrifuging for 2 min;
(9) transferring the separation column into a new ep tube, adding 60 mu L of EB eluent, 12000g/min, and centrifuging for 1 min;
(10) the DNA concentration and purity of each sample were measured by nanodrop 2000.
4. Metagenomic sequencing
After the DNA samples are randomly interrupted, a PE150 strategy of an Illumina Novaseq sequencing platform is adopted to carry out metagenome sequencing on each sample, and each sample generates 6-12G clean reads.
5. Data analysis
Using the metagenome sequencing data quality control software kneaddata to call trimmatic to remove reads with average quality less than 20 and call bowtie2 to compare to a human genome removal host sequence to obtain final reads; evaluating the qualified quality of final reads by fastqc; species annotation with kraken2 to obtain species abundance table; species abundance tables were normalized to relative abundance using R-script.
Wherein species composition impact patterns at the level of intestinal microbiota in the abdominal aortic aneurysm patient group and healthy human group are shown in fig. 2; the results of PCoA analysis based on Bray-Curtis distance for species composition at intestinal microbial species level in the abdominal aortic aneurysm patient group and healthy human group are shown in fig. 3, and the results of displacement multivariate analysis of variance (PERMANOVA) are 7.2232 in F-value and 0.0001 in P-value, indicating that species composition at intestinal microbial species level in the abdominal aortic aneurysm patient group and healthy human group are significantly different.
6. Model construction and evaluation
Using the relative abundance of species as input, numbering 1-64 for 31 healthy people and 33 patients with abdominal aortic aneurysm, generating 30 random numbers of 1-64 by using R language, using people corresponding to corresponding numbers as a training set, using the rest 34 healthy people and patients with abdominal aortic aneurysm as a test set, training the training set by using random forest, predicting by using another data set (test set), evaluating the quality of a model, and readjusting random forest parameters if the accuracy of the phenotype predicted by the test set is lower than 75%; among the healthy persons in the test set shown in fig. 4(a), 13 of 16 persons successfully predict the phenotype as a healthy person, and the prediction success rate is 81.25%, among the abdominal aortic aneurysm patients in the test set shown in fig. 4(b), 14 of 18 persons successfully predict the abdominal aortic aneurysm patients, and the prediction success rate is 77.78%, the preliminary evaluation model is good, the next operation can be performed, the cross-over verification is performed for ten times to check the corresponding microbial population at the lowest error rate, and the intestinal microbial marker is selected according to the cross-over verification result and the Mean precision Decrease (Mean precision Accuracy) importance score, and the error rate is the lowest when the microbial population is 32, which is the best model.
7. Determining gut microbial markers
Selecting the first 30 intestinal microorganisms which are arranged in a Mean precision descending (Mean increment Accuracy) descending order as the intestinal microorganism markers of the abdominal aortic aneurysm, and dividing the intestinal microorganism markers into an intestinal microorganism marker ascending group (AAA ascending) and an intestinal microorganism marker descending group (AAA descending) as shown in figure 5, wherein the number of the intestinal microorganism markers in the AAA ascending group is 25, and the number of the intestinal microorganism markers in the AAA descending group is 5;
wherein, the intestinal microorganism markers of the abdominal aortic aneurysm patient are as follows:
(1)Roseitalea_porphyridii；
(2)Streptomyces_peucetius；
(3)Pseudonocardia_autotrophica；
(4)Agrobacterium_fabrum；
(5)Enterobacter_cloacae_complex_sp._FDA-CDC-AR_0132；
(6)Gordonibacter_pamelaeae；
(7)Neokomagataea_sp._Ha5；
(8)Enterobacter_ludwigii；
(9)Simian_immunodeficiency_virus；
(10)Burkholderia_plantarii；
(11)Burkholderia_multivorans；
(12)Saimiriine_alphaherpesvirus_1；
(13)Actinosynnema_pretiosum；
(14)Georgenia_sp._ZLJ0423；
(15)Amycolatopsis_orientalis；
(16)Acetobacter_persici；
(17)Ruthenibacterium_lactatiformans；
(18)Synechococcus_sp._CB0101；
(19)Xanthomonas_vasicola；
(20)Geobacter_anodireducens；
(21)Cupriavidus_metallidurans；
(22)Adoxophyes_honmai_entomopoxvirus；
(23)Actinomadura_sp._WMMA1423；
(24)Legionella_oakridgensis；
(25)Klebsiella_quasipneumoniae；
the intestinal microbial markers decreased in patients with abdominal aortic aneurysm were as follows:
(1)Haemophilus_parainfluenzae；
(2)Candidatus_Rhodoluna_planktonica；
(3)Vibrio_phage_PWH3a-P1；
(4)Roseburia_intestinalis；
(5)Pseudomonas_asplenii。
8. calculating an intestinal microbial marker index
The abdominal aortic aneurysm enriched intestinal microbial index (AAA acquired microbial index) and the abdominal aortic aneurysm reduced intestinal microbial index (AAA acquired microbial index) of each sample were calculated using the following formulas, respectively:
example 2 evaluation of accuracy of the screened intestinal biomarkers to predict risk of abdominal aortic aneurysm
In the test set, the abdominal aortic aneurysm enriched intestinal microorganism index (AAA acquired microbial index) and the abdominal aortic aneurysm reduced intestinal microorganism index (AAA acquired microbial index) calculated in example 1 were input, and the interclass distribution thereof was as shown in fig. 6, and the identification abilities of the abdominal aortic aneurysm enriched intestinal microorganism and the abdominal aortic aneurysm reduced intestinal microorganism for the abdominal aortic aneurysm were evaluated by the area under the curve (AUC) of the receiver operating characteristic curve (ROC), respectively, and as a result, as shown in fig. 7, the AUC obtained when the abdominal aortic aneurysm enriched intestinal microorganism index (AAA acquired microbial index) was input was 0.8856, the diagnostic identification ability for the abdominal aortic aneurysm was good, the AUC obtained when the abdominal aortic aneurysm reduced intestinal microorganism index (AAA acquired microbial index) was input was 0.9071, and the diagnostic identification ability for the abdominal aortic aneurysm was good.
In order to further embody the accuracy of predicting the risk of abdominal aortic aneurysm by intestinal biomarkers of abdominal aortic aneurysm, the diastolic pressure (SBP), systolic pressure (DBP), Triglyceride (TC), cholesterol (TG), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), homocysteine (Hcy), glucose (glucose) and Uric Acid (UA) indexes of a healthy human group and an abdominal aortic aneurysm patient group are obtained, the distribution among the groups of the indexes is shown in fig. 8, the distribution is respectively used as input in a test set, the identification capability of each index on abdominal aortic aneurysm is evaluated by the area under the curve (AUC) of a characteristic operating curve (ROC) of a subject, and the results are shown in fig. 9, wherein the diastolic pressure (SBP), the systolic pressure (DBP), the Triglyceride (TC), the cholesterol (TG), the High Density Lipoprotein (HDL), the Low Density Lipoprotein (LDL), the homocysteine (Hcy), The AUC values obtained by using glucose (glucose) and Uric Acid (UA) as inputs are 0.6848, 0.6271, 0.5420, 0.6271, 0.6711, 0.5846, 0.7204, 0.5723 and 0.6530, respectively, and thus it can be seen that these clinical indicators considered as risk factors of abdominal aortic aneurysm are significantly less accurate in diagnosis of abdominal aortic aneurysm than intestinal microbial markers.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (10)
1. An intestinal microbial marker of an abdominal aortic aneurysm, wherein the intestinal microbial marker comprises 30 microorganisms,
wherein, the intestinal microorganism markers of the abdominal aortic aneurysm patient are as follows:
(1)Roseitalea_porphyridii；
(2)Streptomyces_peucetius；
(3)Pseudonocardia_autotrophica；
(4)Agrobacterium_fabrum；
(5)Enterobacter_cloacae_complex_sp._FDA-CDC-AR_0132；
(6)Gordonibacter_pamelaeae；
(7)Neokomagataea_sp._Ha5；
(8)Enterobacter_ludwigii；
(9)Simian_immunodeficiency_virus；
(10)Burkholderia_plantarii；
(11)Burkholderia_multivorans；
(12)Saimiriine_alphaherpesvirus_1；
(13)Actinosynnema_pretiosum；
(14)Georgenia_sp._ZLJ0423；
(15)Amycolatopsis_orientalis；
(16)Acetobacter_persici；
(17)Ruthenibacterium_lactatiformans；
(18)Synechococcus_sp._CB0101；
(19)Xanthomonas_vasicola；
(20)Geobacter_anodireducens；
(21)Cupriavidus_metallidurans；
(22)Adoxophyes_honmai_entomopoxvirus；
(23)Actinomadura_sp._WMMA1423；
(24)Legionella_oakridgensis；
(25)Klebsiella_quasipneumoniae；
the intestinal microbial markers decreased in patients with abdominal aortic aneurysm were as follows:
(1)Haemophilus_parainfluenzae；
(2)Candidatus_Rhodoluna_planktonica；
(3)Vibrio_phage_PWH3a-P1；
(4)Roseburia_intestinalis；
(5)Pseudomonas_asplenii。
2. use of the intestinal biomarker for abdominal aortic aneurysm of claim 1 as predictor for early screening of abdominal aortic aneurysm.
3. Use of an intestinal biomarker for an abdominal aortic aneurysm as claimed in claim 1 in the manufacture of a tool for early screening or prediction of an abdominal aortic aneurysm.
4. The use of claim 3, wherein the tool for early screening or prediction of an abdominal aortic aneurysm comprises an early screening or pretest kit for an abdominal aortic aneurysm.
5. The use of claim 4, wherein the early abdominal aortic aneurysm screening or pretesting kit comprises a detection reagent for an intestinal microbial marker of an abdominal aortic aneurysm of claim 1.
6. The use of claim 5, wherein the detection reagent comprises a primer specific for a gut microbial marker of abdominal aortic aneurysm as claimed in claim 1.
7. Use of an intestinal microbial marker of an abdominal aortic aneurysm as claimed in claim 1 in the manufacture of a medicament for the treatment of an abdominal aortic aneurysm.
8. The use according to claim 7 for the preparation or screening of a medicament for the treatment of abdominal aortic aneurysm targeting the intestinal biomarker of abdominal aortic aneurysm as claimed in claim 1.
9. The use according to claim 7, wherein the medicament acts on the intestinal biomarker of abdominal aortic aneurysm as defined in claim 1.
10. Use of the intestinal biomarker for abdominal aortic aneurysm of claim 1 for predicting the individual treatment efficacy of an abdominal aortic aneurysm patient.
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| CN109852714A (en) * | 2019-03-07 | 2019-06-07 | 南京世和基因生物技术有限公司 | A kind of early diagnosis of intestinal cancer and Diagnosis of Pituitary marker and purposes |
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| GB1499351A (en) * | 1974-01-23 | 1978-02-01 | Wirostko E | Process for producing a micro-organism |
| CN109852714A (en) * | 2019-03-07 | 2019-06-07 | 南京世和基因生物技术有限公司 | A kind of early diagnosis of intestinal cancer and Diagnosis of Pituitary marker and purposes |
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