CN116949165B - Fecal marker panel for assessing anxiety/depression-breast cancer co-morbidity and uses thereof - Google Patents
Fecal marker panel for assessing anxiety/depression-breast cancer co-morbidity and uses thereof Download PDFInfo
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Abstract
The invention discloses a fecal marker group for evaluating anxiety/depression-breast cancer co-morbidity and application thereof. The inventor finds that the deprivation of intestinal flora can reverse anxiety and depression behaviors and carcinomatous effect caused by chronic mental stress, and the content of Achroman and butyric acid in the faeces of mice in a stress group is obviously reduced. Among 57 breast cancer patients, anxiety and depression states of the patients are evaluated through HADS scoring, 16s rDNA sequencing, qPCR verification and targeted short-chain metabolome detection are carried out on patient faeces, and the fact that the content of Ackermann bacteria and butyric acid in the faeces of the breast cancer patients with anxiety and depression emotion is obviously reduced is found, and the high content of the Ackermann bacteria and the butyric acid is obviously inversely related to the size, grading, distal metastasis, ki67 and tumor marker CA153 expression quantity of the breast cancer. The oral administration of the Ackermans and the sodium butyrate can inhibit the breast cancer progress and anxiety and depression behaviors of the pressure mice, and provide clinical diagnosis and treatment guidance for patients suffering from anxiety/depression-breast cancer.
Description
Technical Field
The invention belongs to the field of medical diagnosis, and particularly relates to a fecal marker group for evaluating anxiety/depression-breast cancer co-morbidity and application thereof.
Background
Clinical studies show that tumor patients often suffer from chronic mental stress, and 54.9% and 49.7% of Chinese cancer patients suffer from chronic mental stress symptoms of depression and anxiety 1 And chronic stress can increase the death risk of tumor patients 2 . Recent studies have shown that chronic mental stress is mainly caused by abnormal release of stress-related hormones through activation of the Sympathetic Nervous System (SNS) and hypothalamic-pituitary-adrenal (HPA) axes, thereby promoting various malignant phenotypes such as tumor metastasis, proliferation, angiogenesis and immune escape 2 . For example, chronic stress may activate the HP A axis to release epinephrine and thereby activate ADRB2 receptor up-regulating MYC transcription activation SLUG, thereby promoting breast cancer dryness 3 . Therefore, the key to improving the tumor treatment effect and improving the life quality of the patient is to pay close attention to the emotion change and psychological state of the tumor patient, provide psychological consultation in time and conduct psychological coaching intervention. The Hospital Anxiety Depression Scale (HADS) is a 'gold standard' for the current clinical self-evaluation of the anxiety depression state of patients, but the scale is highly subjective and is easily interfered by objective factors, and sometimes cannot well reflect the mental and psychological state of the patients, thus delaying the 'gold window' of treatment. Therefore, the search for noninvasive, convenient, objective and accurate anxiety/depression-breast cancer co-morbidity early diagnosis and postoperative detection methods is a constant effort of researchersThe direction of the force.
Detection of changes in the flora in feces is currently a trend in noninvasive diagnosis of tumor patients. Intestinal flora homeostasis plays a key role in maintaining normal physiological functions of the body, and dysbacteriosis can lead to malignant progression of tumors. For example, in comparison to healthy humans, early stage colon cancer patients are enriched in coliform bacteria (expressing clbB) and bacteroides fragilis (expressing bft) secreting oncogenic toxins in the colonic mucosa 4 . Recent studies have found that chronic stress can promote the development of a variety of diseases by interfering with intestinal flora homeostasis. For example, chronic stress causes abnormal release of glucocorticoid to increase intestinal permeability, and further stimulates G-CSF production by activating Th17 cells to release IL-17A by the arthrobacter, promoting sickle cell disease 5 . However, the regulatory mechanisms by which chronic mental stress causes disturbances in the intestinal flora in promoting tumor progression are still unclear.
Recent studies have found that ackermanni is considered a biomarker for healthy intestinal tract 6,7 Its abundance is inversely related to tumor progression 8 . For example, amuc_1100 protein expressed on the outer membrane of Acremonium by promoting CD8 + Expansion and activation of T cells to slow progression of colorectal cancer 9 . In addition, the extramembranous protein Amuc_1100 produced by Ackermana Δ80 Can reduce inflammatory reaction and HPA axis activity by inducing serotonin biosynthesis and activation of 5-HTR1A-CREB-BDNF pathway, thereby relieving depression-like symptoms of mice caused by chronic stress 10 . Although ackermannia can improve the anxiety-depression state induced by chronic mental stress, ackermannia can reverse the tumor progression promoted by chronic mental stress, and is still to be further studied as a new marker for anxiety/depression-breast cancer co-disease diagnosis.
As an important medium for the functions of intestinal flora, the metabolites of the intestinal bacteria play an important role in maintaining the normal physiological homeostasis of the organism, regulating host immunity, metabolism and other aspects of development. Short Chain Fatty Acids (SCFAs) are important intestinal bacteria metabolites, are small molecules synthesized by specific intestinal bacteria through dietary fiber fermentation, and can inhibit tumor progression 11 . For example, butylPromotion of downstream target gene Fas, P21, P27 expression by acid through inhibition of HDAC3 activity causes cell cycle arrest, thereby inducing apoptosis of lymphoma cells 12 . In addition, butyric acid can cause apoptosis in human colon tumor cells by activating the G protein-coupled receptor GPR43 to up-regulate the expression of the pro-apoptotic protein Caspase 3/6/7/8 13 . Recent studies have found that anaplerotic acid in mice can reverse anxiety-depressive behavior due to chronic stress 14 . However, whether in vivo back-patch acid can reverse the carcinomatous effect caused by chronic mental stress and whether butyric acid can be used as a novel marker to evaluate anxiety-depressive states of breast cancer patients remains to be further explored.
Disclosure of Invention
The object of the present invention is to overcome at least one of the disadvantages of the prior art and to provide a fecal marker panel for assessing anxiety/depression-breast cancer co-morbidity and uses thereof.
The technical scheme adopted by the invention is as follows:
in a first aspect of the invention, there is provided:
a fecal marker panel for assessing anxiety/depression-breast cancer co-morbidity consisting of ackerman and butyric acid in feces.
In a second aspect of the invention, there is provided:
the application of the detection reagent in preparing the anxiety/depression-breast cancer co-morbidity diagnosis reagent is characterized in that a sample detected by the detection reagent is feces, and quantitative markers are Ackermans bacteria and butyric acid in the feces.
In some examples of application, the ackermannia is quantified by methods of metagenomics, 16s rDNA sequencing (16 s rDNA seq) or qPCR.
In some examples of applications, butyric acid is quantified by gas chromatography-mass spectrometry (GC-MS).
In a third aspect of the invention, there is provided:
a system for assessing anxiety/depression-breast cancer co-morbidity comprising:
the quantifying device is used for quantifying the content of the Acremonium and the butyric acid in the fecal sample;
an analysis device for evaluating the risk of anxiety/depression-breast cancer co-morbidity based on the quantitative result of the quantitative device;
and a result output device for outputting the analysis result of the analysis device.
In some examples of the system, the quantification device comprises a macrogenomic device to quantify ackermannia, a 16s rDNA seq quantification or a qPCR analysis device.
In some examples of the system, the quantification device comprises a GC-MS device that quantifies butyric acid.
In some examples of the system, the amounts of ackermanni and butyric acid were significantly reduced, indicating a high risk of anxiety/depression-breast cancer co-morbidity.
In some system examples, acremonium DNA content greater than or equal to 1.382 μg/g patient stool DNA and butyric acid content greater than or equal to 1080 μg/g patient stool, indicating low anxiety depression.
In a fourth aspect of the invention, there is provided:
a composition for improving anxiety/depression-breast cancer co-morbidity symptoms comprises an active ingredient and acceptable auxiliary materials, wherein the active ingredient is Acremonium and pharmaceutically acceptable butyrate.
In some examples of compositions, the ratio of ackermanni to butyric acid is: the gastric lavage dosage of the Ackermana is (1-9) multiplied by 10 8 CFU, pharmaceutically acceptable butyrate, is used in the form of (100-400) mg/kg.
In some examples of compositions, the pharmaceutically acceptable butyrate is sodium butyrate.
The beneficial effects of the invention are as follows:
the invention breaks through the limitation that anxiety/depression can be determined only through subjective evaluation in the prior art, and discovers that a specific fecal marker can be used as an objective index for evaluating the risk of anxiety/depression-breast cancer co-morbidity, and is hopeful to obtain a more accurate result.
Based on the earlier study foundation, the inventors first constructed a mouse model of anxiety/depression-breast cancer co-morbidity. Meanwhile, in order to study the role of intestinal flora in promoting tumor progression by chronic mental stress,a sterile mouse model of intestinal flora colonization was used and subcutaneously tumorigenic female mice were randomly divided into a specific pathogen free (Specific pathogen Free, SPF) mouse control group, an SPF mouse-imposed chronic stress group, a sterile (Germ-free, GF) mouse control group and a GF mouse-imposed chronic stress group. The detection result of the behavioural experiment shows that the mice in the stress group show obvious anxiety-like behavior compared with the mice in the control group in the SPF mice, and the tumor volume of the mice treated by the confinement is obviously larger than that of the mice in the control group. Whereas deprivation of intestinal flora in GF mice reversed anxiety-like behavior due to chronic mental stress and reversed the promotion of tumor by stress (fig. 1). Then, metagenome sequencing is carried out by collecting the faeces of the SPF mice in the pressure group and the control group mice, and the Ackermania in the faeces of the mice in the pressure group is found outAkkermansia mucinphila) The abundance decreases significantly. Based on the results of KEGG pathway enrichment analysis of the sequencing results, the inventors performed Short Chain Fatty Acid (SCFAs) targeted metabonomics detection of mouse faeces and breast cancer tumor tissue, and found that the butyric acid (butyl acid) content in faeces and tumor tissue from pressure group mice was significantly reduced. Spearman correlation analysis showed that the abundance of ackerman was positively correlated with the amount of butyric acid in mouse faeces and tumors (figure 2).
To demonstrate that ackerman and butyric acid found in the mouse experiments can be used as non-invasive molecular markers for diagnosis of anxiety/depression-breast cancer co-morbidity, the inventors recruited 57 breast cancer patients, and evaluated their anxiety-depression status by HADS scoring the patients. By 16s rDNA sequencing of the faeces of clinical patients, the abundance of Ackermana in the faeces of breast cancer patients with anxiety-depression emotion was found to be significantly reduced, while the results of the targeted metabonomics also indicate that the butyric acid content in the faeces of breast cancer patients with anxiety-depression was significantly reduced (figure 3). Spearman correlation analysis showed that the abundance of ackerman bacteria in the feces was significantly positively correlated with the butyrate content, while HADS scores were significantly negatively correlated with the ackerman bacteria abundance and butyrate content in the patient's feces (fig. 4). Next, the inventors rank the patients according to the abundance of ackermannia and the content of butyric acid, and classify the patients into ackermannia high (high) and ackermannia low (low), butyric acid high (high) and butyric acid low (low). Patients with ackerman high and butyric acid high were found to be significantly inversely related to tumor size, grade, distant metastasis, ki67, tumor marker CA153 (tables 1 and 2).
The inventor in the mouse experiment finds that the in vivo anaplerosis and butyric acid can significantly reverse the tumor progress promoted by chronic mental stress through the gastric lavage mode, and can reverse the anxiety-like behavior (figure 5) of the mouse caused by chronic stress, and the studies show that the anaplerosis and the butyric acid can be used for noninvasive molecular markers for diagnosis of anxiety/depression-breast cancer co-morbidity, and can better guide clinical medication.
Drawings
FIG. 1 is the results of a gut flora-mediated chronic mental stress to promote tumor growth and a mouse behavioral assay.
Figure 2 is the result of mouse fecal metagenomics and targeted metabolomics.
FIG. 3 shows the results of stool 16s rDNA sequencing and targeted metabonomics from breast cancer patients.
FIG. 4 shows the results of analysis of correlation between HADS and Acremonium abundance and butyric acid content.
FIG. 5 is the result of anaplerotic Achroman and butyric acid reversal of chronic mental stress cancer promotion.
Detailed Description
In a first aspect of the invention, there is provided:
a fecal marker panel for assessing anxiety/depression-breast cancer co-morbidity consisting of ackerman and butyric acid in feces.
In a second aspect of the invention, there is provided:
the application of the detection reagent in preparing the anxiety/depression-breast cancer co-morbidity diagnosis reagent is characterized in that a sample detected by the detection reagent is feces, and quantitative markers are Ackermans bacteria and butyric acid in the feces.
The method of quantifying ackermanni may be an existing method. In some examples of application, ackermannia is quantified by methods of metagenomics, 16s rDNA seq, or qPCR. These methods are relatively mature, reliable in detection results and low in cost.
The method for quantifying butyric acid may be an existing method. In some examples of applications, butyric acid is quantified by GC-MS method. These methods are relatively mature, reliable in detection results and low in cost.
In a third aspect of the invention, there is provided:
a system for assessing anxiety/depression-breast cancer co-morbidity comprising:
the quantitative device is used for quantifying the amounts of the Acremonium and the butyric acid in the fecal sample;
an analysis device for evaluating the risk of anxiety/depression-breast cancer co-morbidity based on the quantitative result of the quantitative device;
and a result output device for outputting the analysis result of the analysis device.
In some examples of the system, the quantification device comprises a macrogenomic device to quantify ackermannia, a 16s rDNA seq quantification or a qPCR analysis device.
In some examples of the system, the quantification device comprises a GC-MS device that quantifies butyric acid.
The quantitative device is mature, and the reliability of the detection result is high. Of course, other known dosing devices may be used.
In some examples of the system, the amounts of ackermanni and butyric acid were significantly reduced, indicating a high risk of anxiety/depression-breast cancer co-morbidity. Significantly reduced to what is known in the art means that the amount of ackermanni or butyric acid is below the median, or below the average level.
In some system examples, acremonium DNA content greater than or equal to 1.382 μg/g patient stool DNA and butyric acid content greater than or equal to 1080 μg/g patient stool, indicating low anxiety depression.
In a fourth aspect of the invention, there is provided:
a composition for improving anxiety/depression-breast cancer co-morbidity symptoms comprises an active ingredient and acceptable auxiliary materials, wherein the active ingredient is Acremonium and pharmaceutically acceptable butyrate.
In some examples of compositions, the composition is a gastric lavage or an oral dosage.
In some examples of compositions, the ratio of ackermanni to pharmaceutically acceptable butyrate is: the gastric lavage dosage of the Ackermana is (1-9) multiplied by 10 8 CFU and butyric acid are used for lavage (100-400) mg/kg.
The pharmaceutically acceptable butyrate may be various pharmaceutically acceptable salts, such as sodium, potassium, calcium, zinc salts, and in some examples of compositions, the pharmaceutically acceptable butyrate is sodium butyrate. Sodium butyrate is low in price, has better water solubility and is a better choice.
The technical scheme of the invention is further described below in conjunction with experiments.
1. Construction and verification of chronic mental stress mouse model
Animal experiments are strictly referred to the management requirements of the tumor animal experiment center of Dalian medical university and are implemented after ethical examination. To construct a mouse model of anxiety/depression-breast cancer co-morbidity, the inventors randomly divided SPF mice and GF mice into 4 groups, SPF mouse control group, SPF mouse-applied chronic stress group, GF mouse control group, GF mice-applied chronic stress group (10 per group). Py8119-pLVX-MCS-Luc2 cells from mice were pre-treated with chronic confinement for 1 week and 1X 10 per 100. Mu.l 5 The concentration of individual cells was resuspended in PBS buffer and the cells were inoculated subcutaneously into the backs of 7 week old female mice. The tumor growth of the mice was recorded after the transplanted tumors had grown to an average diameter of about 3 mm. The mice in the stress group were subjected to the confinement experiment for 6 hours each day for 4 weeks without undue stress and injury to the mice during the confinement experiment (fig. 1, A).
Anxiety-like behavior of the chronic stress mice is detected through an open field and elevated plus maze behavioural experiment, and whether the chronic stress modeling is successful is evaluated. a. Open field experiments: the open field experimental device is divided into a central area and a peripheral area. At the beginning of the experiment, the mice were placed at the corners of the peripheral area and after free movement for 5 minutes, anxiety states of the mice were reflected by analyzing data such as the moving distance, standing times, and center residence time of the mice. b: overhead plus maze experiment: overhead cross maze experimental deviceThe device consists of an open arm and a closed arm. At the beginning of the experiment, mice were left on the central platform to explore freely for 5 minutes, and the time and distance of movement into the open and closed arms were recorded to reflect the anxiety state of the mice. The behavioral test results indicate that stress group mice exhibited anxiety-like behavior in SPF mice, while elimination of intestinal flora in GF mice significantly reversed stress-induced anxiety-like behavior in mice (fig. 1B and C). The tumor volume of the mice was measured once every two days according to the formula v= (long diameter x short diameter 2 ) And (2) calculating. Both the in vivo imaging results of mice and the tumorigenic profile of tumors showed that the tumor volume of the pressure group mice was significantly greater than the control group in SPF mice, while deprivation of intestinal flora was able to significantly reverse the tumor promotion by pressure (fig. 1D and E). The experimental results show that the chronic mental stress can further cause anxiety depression-like behaviors of the mice by influencing the homeostasis of intestinal flora of the mice and finally promote the tumor progression of the mice with breast cancer, and the elimination of the intestinal flora in the mice can reverse the promotion effect of the chronic mental stress on the tumor of the mice with breast cancer.
2. Mouse fecal metagenomic and targeted metabonomic analysis
To further investigate the effect of chronic mental stress on the intestinal flora of mice, the inventors collected fresh faeces of mice and frozen faecal samples in liquid nitrogen. The total DNA of microorganisms in the feces was extracted using an e.z.n.a. oven DNA Kit (D4015-02, omega, inc., USA) Kit, and the quality of DNA extraction was detected by agarose gel electrophoresis, while the DNA was quantified using an ultraviolet spectrophotometer. Macrogenomic sequencing is carried out on the extracted fecal DNA, and the analysis result of LEfSe (lineardiscriminant analysis (LDA) effect size) shows that the Ackermania in the feces of the mice in the pressure group at the seed levelAkkermansia mucinphila) The significantly reduced abundance (fig. 2A and B), the results of qPCR of mouse fecal DNA also demonstrated a significant decrease in ackermannia abundance under stress (fig. 2C), indicating that ackermannia abundance was most significantly altered by stress in the breast cancer mouse model. Further the inventors performed KEGG pathway enrichment analysis on the sequencing results, found that fatty acid synthesis in the 10 th position before the changeThe pathways and fatty acid metabolic pathways were significantly enriched (fig. 2D). Based on the analysis results of KEGG, the inventors performed SCFAs-targeted metabonomics detection on the faeces and breast cancer tumor tissue of mice, and found that the butyric acid (butyric acid) content in the faeces and tumor tissue of pressure group mice was significantly reduced (fig. 2E and F). Meanwhile, the Spearman correlation analysis result shows that the abundance of the ackerman bacteria in the mouse feces is obviously and positively correlated with the content of the butyric acid in the feces and the content of the butyric acid in the tumor tissues (figures 2G and H).
3. Fecal 16s rDNA sequencing and targeted metabonomics analysis of breast cancer patients
After obtaining approval by the ethical review Committee of the affiliated second hospital of Dalian medical university, the inventors collected stool samples from 57 breast cancer patients in total for evaluation of the abundance of Ackermans and the butyric acid content in the stool. Furthermore, to further demonstrate that ackerman and butyric acid in the stool of patients can be used as non-invasive molecular markers for diagnosis of anxiety/depression-breast cancer co-diseased patients, the inventors performed HADS scoring on 57 breast cancer patients to assess anxiety-depression status of the patients. According to the criteria, a score of 10 was defined as no/low anxiety depression patients (HADS low) and a score of > 10 was defined as medium/severe anxiety depression patients (HADS high).
Next, the collected feces of 57 patients were subjected to DNA extraction and 16s rDNA sequencing, and the analysis result of volcanic chart showed that the abundance of ackermannin bacteria in feces was significantly reduced in breast cancer patients suffering from moderate/severe anxiety depression emotion (fig. 3A), the same conclusion was drawn from the heat chart analysis result (fig. 3B), and the result of qPCR also showed that the content of ackermannin bacteria was significantly reduced in feces from breast cancer patients suffering from anxiety depression (fig. 3C). Further examination of stool SCFAs using targeted metabonomics, the analysis also showed a significant decrease in butyrate content in the stool of patients with anxiety-depression breast cancer (figure 3D), consistent with the results obtained in the mouse experiments. Spearman correlation analysis showed that the abundance of ackerman bacteria in the stool was significantly positively correlated with the butyrate content (fig. 4A), while HADS scores were significantly negatively correlated with ackerman bacteria abundance and butyrate content in the stool (fig. 4B and C). To further confirm that ackerman and butyric acid can be novel markers of anxiety/depression-breast cancer co-morbidity, the inventors rank the patients according to abundance of ackerman and content of butyric acid, and take median as a boundary value, and divide the patients into ackerman high and ackerman low, butyric acid high and butyric acid low. The high ackermann abundance and butyrate content were found to be significantly inversely correlated with tumor size, grade, distant metastasis, ki67, tumor marker CA153 (tables 1 and 2).
TABLE 1 correlation of Ackermansia with clinical indicators
Statistical significance was determined by a two-tailed unpaired Student's t test.
TABLE 2 correlation of butyric acid with clinical indicators
Statistical significance was determined by a two-tailed unpaired Student's t test.
The research results show that the marker composed of the intestinal flora Acremonium and the metabolite butyric acid thereof in the feces can well reflect the anxiety depression degree of a breast cancer patient, can accurately predict the tumor grading and metastasis risks of the breast cancer patient, and can serve as a new tumor marker for noninvasive diagnosis of the breast cancer.
4. Analysis of effects of anaplerotic ackerman and butyric acid in mouse transplantation tumor model
Finally, the inventor verifies in a mouse model through in vivo anaplerotic ackermanni and sodium butyrate. The inventors randomly divided mice into 4 groups, control group, chronic stress group, and Hui's Ackermans group (3×10) 8 CFU/day), pressure and pressure supplemented Ackermans group (3×10) 8 CFU/day, 8 per group). After 1 week of chronic confinement pretreatment, mice-derived Py8119-pLVX-MCS-Luc2 cells were enriched with 1X 10 per 50. Mu.l 5 Concentration of individual cells resuspended in PBS bufferIn solution, and cells were inoculated in situ into the fourth pair of mammary fat pads of 7 week old female mice (fig. 5A). The tumor growth of the mice was recorded after the transplanted tumors had grown to an average diameter of about 3 mm. The inventors found that anaplerotic ackermannia was able to reverse chronic stress induced anxiety-like behavior in mice by intragastric administration (fig. 5B and C), and that in vivo imaging results and mouse tumorigenesis curves indicate that anaplerotic ackermannia was able to significantly reverse chronic stress-promoted tumor progression (fig. 5D and E). At the same time, similar results were found in the control, chronic stress, anaplerotic sodium butyrate (200 mg/kg/day), and pressure plus anaplerotic sodium butyrate (8 per group) 4 experiments (FIG. 5F-J). These results indicate that ackerman and butyric acid can be used as non-invasive molecular markers for diagnosis of anxiety/depression-breast cancer co-morbidity and better guide clinical medication.
In conclusion, experimental data show that quantitative analysis of the abundance and the butyric acid content of the Ackermans in the feces provides a novel high-sensitivity and specific detection index for diagnosis of patients suffering from anxiety/depression-breast cancer, has a good diagnosis value for the patients suffering from anxiety/depression, reduces missed diagnosis, and simultaneously, the Ackermans and the butyric acid can be used as good independent prognosis prediction indexes, thereby providing a novel approach for diagnosing anxiety depression states and predicting of the patients suffering from breast cancer.
The above description of the present invention is further illustrated in detail and should not be taken as limiting the practice of the present invention. It is within the scope of the present invention for those skilled in the art to make simple deductions or substitutions without departing from the concept of the present invention.
Reference is made to:
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Claims (9)
1. the application of the detection reagent in preparing the diagnosis reagent for the anxiety/depression-breast cancer co-morbidity of the breast cancer patients is characterized in that a sample detected by the detection reagent is feces, and quantitative markers are Ackermans bacteria and butyric acid in the feces.
2. The use according to claim 1, characterized in that the quantification of ackermannia is performed by means of metagenomics, 16s rDNA sequencing or qPCR.
3. The use according to claim 1, characterized in that the butyric acid is quantified by means of a gas chromatography-mass spectrometry combination.
4. A system for predicting anxiety/depression in a breast cancer patient, comprising:
the quantitative device is used for quantifying the amounts of the Acremonium and the butyric acid in the fecal sample;
an analysis device for evaluating the risk of anxiety/depression-breast cancer co-morbidity based on the quantitative result of the quantitative device;
and a result output device for outputting the analysis result of the analysis device.
5. The system of claim 4, wherein the quantifying means comprises:
a macrogenomic apparatus for quantifying ackermann bacteria, a 16s rDNA seq quantification or qPCR analysis apparatus; and/or GC-MS device for quantifying butyric acid.
6. The system of claim 4, wherein a significant decrease in the amount of ackerman and butyric acid is indicative of a high risk of anxiety/depression-breast cancer co-morbidity.
7. The system of claim 4, wherein an ackermannia DNA content of greater than or equal to 1.382 μg per 1g patient stool DNA and a butyric acid content of greater than or equal to 1080 μg per 1g patient stool is indicative of low anxiety depression.
8. A composition for improving anxiety/depression-breast cancer co-morbidity symptoms comprises an active ingredient and acceptable auxiliary materials, and is characterized in that the active ingredient is Acremonium and pharmaceutically acceptable butyrate.
9. The composition of claim 8, wherein the ratio of ackermanni to sodium butyrate is: the gastric lavage dose of Ackermana is 1×10 8 CFU to 9×10 8 CFU, a pharmaceutically acceptable butyrate, was used at a lavage dose of 100 mg/kg to 400 mg/kg.
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