Alterations of Gut Microbiome in the Frontline Medical Staff Under the Stress

Stress Disorders, Post-Traumatic Clinical Trial

— AGMFMSS  

Official title:

Alterations of Gut Microbiome in the Frontline Medical Staff Under the Stress of Fighting Against 2019-nCoV

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04443075
• Other study ID #: XJTU1AF2020LSK-022
• Status: Completed
• Start date: June 24, 2020
• Est. completion date: December 24, 2020

Study information

• Verified date: March 2021
• Source: First Affiliated Hospital Xi'an Jiaotong University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

With the outbreak of 2019 novel coronavirus (2019-nCoV), the frontline medical workers faced enormous stress, including a high risk of infection and inadequate protection from contamination, isolation, patients with negative emotions, a lack of contact with their families, and exhaustion, which may cause mental health problems. The investigators plan to collect the faecal samples and clinical assessments from a part of frontline medical workers in three time points to analyse the changing profile of gut microbiome according to outcomes of 16s rRNA sequencing. The samples from the matched health controls will also be sequenced to compare with the exposed group in gut microbiome community.

Description:

In December, 2019, a novel coronavirus outbreak of pneumonia emerged in Wuhan, Hubei province, China, and has subsequently spread to more than 30 provinces in China and almost 100 countries in the world. In the fight against the 2019 novel coronavirus (2019-nCoV), medical workers in Wuhan have been facing enormous stress, including a high risk of infection and inadequate protection from contamination, isolation, patients with negative emotions, a lack of contact with their families, and exhaustion. The severe situation is causing mental health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger, and fear. These mental health problems could also cause posttraumatic stress (PTS) symptoms in a lasting time. A research examining the psychological impact of the 2003 outbreak of severe acute respiratory syndrome on hospital empoyees found that about 10% of the respondents had experienced high leves of PTS symptoms since the SARS outbreak.

Microbiome-gut-brain (MGB) axis has been validated in expanding studies, which means there are bidirectional communication between commensal organisms within the gut and the brain. Gut microbiota may influence brain function through neural, endocrine, and immune pathways. For example, substances produced by the gut microbiota may be absorbed reaching the brain by the blood stream. The brain, in turn, may influence the gut microbiota trough neuronal and endocrine pathways. In recent years, many reseaches support the relevance of microbiota and mental health status. Bercik et al. transplanted microbiota from adult germ-free (GF) BALB/c mice (a high-anxiety mouse strain) into adult GF NIH Swiss mice (a low-anxiety mouse strain), then found the behavioral profile of the donor was evident in the recipient animal, showing that the microbiota can directly affect behavior. Moreover, preclinical studies have shown that stress and emotions, including maternal separation and restraint, heat, and acoustic stress, alters the composition of the gut microbiota, maybe through the release of stress hormones or sympathetic neurotransmitters that influence gut physiology and alter the habitat of the microbiota. In addition, researchers found that stress has the ability to increase intestinal permeability, probably through the involvement of corticotrophin releasing factor and its receptors (CRFR1 and CRFR2), which play a key role in stress-induced gut permeability dysfunction. Increased intestinal permeability provides bacteria an opportunity to translocate across the intestinal mucosa and directly access both the immune and neuronal cells of the enteric nervous system (ENS). Stress also activates the autonomic nervous system, which affects gastric acid, bile, and mucus secretion, as well as gut motility. Gut motility is of particular importance since it is strongly associated with gut microbiota composition and richness. Based on these researches, the gut microbiome increasingly deserve attention to understand psychiatric disorders.

Therefore, the present study aim to collect the faecal samples and clinical assessments from a part of frontline medical workers in three time points to analyse the changing profile of gut microbiome according to outcomes of 16s rRNA sequencing. The samples from the matched health controls will also be sequenced to compare with the exposed group in gut microbiome community.

Methods Study design and sample collection The frontline workers in First Affiliated Hospital of Xi'an Jiaotong University will be included if they conformed with (1) taking part in the medical team to support Wuhan, (2) of 18 to 50 years old, (3) did not take antibiotics within 3 months before sample collection, (4) 17.5250ml or beer>1bottle) or the previous day (liquor>50ml or beer>50ml). All included persons should provide signed informed consent before sample collection, and the protocol was approved by the Ethics Committee of First Affiliated Hospital of Xi'an Jiaotong University (KYLLSL-2020-043). Faecal samples from each staff should be freshly collected at the hospital and frozen at -80℃ using specified faecal collector.

Clinical assessmant PHQ-15, PHQ-9, GAD-7, PSQI, SCL-90, and IES-R will be used for the assessment of clinical symptoms related to psychiatric disorder for exposed group in three time point and non-exposed group.

DNA extraction and 16S rRNA sequencing The investigators will perform 16S rRNA sequencing for all the collected faecal samples. Briefly, bacterial genomic DNA will be extracted, and the 16S rRNA whole region will be amplified by PCR, and then sequenced.

Statistical analysis The 16S rRNA sequencing data will be analysed using Quantitative Insights Into Microbial Ecology (QIIME). The investigators then use usearch to cluster sequences into taxonomic units (OTUs) at 97% identity and construct the OTU table. Microbial community structure, alpha diversity, and beta diversity will be analysed. LEfSe analysis, and random forest analysis will be used to find the biomarker between different group. Spearman's rank correlation will be used to identify the corrolation between clinical assessments and stress-associated microbiome.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: December 24, 2020
• Est. primary completion date: December 4, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• taking part in the medical team to support Wuhan

• of 18 to 50 years old

• did not take antibiotics within 3 months before sample collection

• 17.5<body mass index (BMI)<30

Exclusion Criteria:

• have serious cardiovascular disease, blood disease, and endocrine disease

• have a history of cancer or its complications

• have active gastrointestinal diseases or complications and serious systemic diseases

• have history of brain organic diseases or complications and mental retardation

• have mental disorders such as mood disorder and anxiety disorders

• pregnant or lactating

• drink in the past week (liquor>250ml or beer>1bottle) or the previous day (liquor>50ml or beer>50ml)

Related Conditions & MeSH terms

• Stress Disorders, Post-Traumatic

Intervention

Device:
• faecal sample collector
The frontline medical workers mainly exposed under the stress of fighting against 2019-nCoV

Locations

Country	Name	City	State
China	First Affiliated Hospital of Xian Jiaotong University	Xi'an	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
First Affiliated Hospital Xi'an Jiaotong University

Country where clinical trial is conducted

China, 

References & Publications (6)

Foster JA, McVey Neufeld KA. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013 May;36(5):305-12. doi: 10.1016/j.tins.2013.01.005. Epub 2013 Feb 4. Review. — View Citation

Kang L, Li Y, Hu S, Chen M, Yang C, Yang BX, Wang Y, Hu J, Lai J, Ma X, Chen J, Guan L, Wang G, Ma H, Liu Z. The mental health of medical workers in Wuhan, China dealing with the 2019 novel coronavirus. Lancet Psychiatry. 2020 Mar;7(3):e14. doi: 10.1016/S2215-0366(20)30047-X. Epub 2020 Feb 5. — View Citation

Malan-Muller S, Valles-Colomer M, Raes J, Lowry CA, Seedat S, Hemmings SMJ. The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders. OMICS. 2018 Feb;22(2):90-107. doi: 10.1089/omi.2017.0077. Epub 2017 Aug 2. Review. — View Citation

Rieder R, Wisniewski PJ, Alderman BL, Campbell SC. Microbes and mental health: A review. Brain Behav Immun. 2017 Nov;66:9-17. doi: 10.1016/j.bbi.2017.01.016. Epub 2017 Jan 25. Review. — View Citation

Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet. 2020 Feb 15;395(10223):470-473. doi: 10.1016/S0140-6736(20)30185-9. Epub 2020 Jan 24. Erratum in: Lancet. 2020 Jan 29;:. — View Citation

Wu P, Fang Y, Guan Z, Fan B, Kong J, Yao Z, Liu X, Fuller CJ, Susser E, Lu J, Hoven CW. The psychological impact of the SARS epidemic on hospital employees in China: exposure, risk perception, and altruistic acceptance of risk. Can J Psychiatry. 2009 May;54(5):302-11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Gut microbiome composition of exposed group	Gut microbiome composition will be anaylysed using 16S rRNA sequencing.	immediately after the frontline workers come back to Xi'an
Primary	Gut microbiome composition of exposed group	Gut microbiome composition will be anaylysed using 16S rRNA sequencing.	immediately after the frontline workers isolated for two weeks
Primary	Gut microbiome composition of exposed group	Gut microbiome composition will be anaylysed using 16S rRNA sequencing.	immediately after the frontline workers going back to normal work for one month
Primary	Gut microbiome composition of non-exposed group	Gut microbiome composition will be anaylysed using 16S rRNA sequencing.	During the procedure of collecting faecal samples from exposed group
Primary	The Impact of Event Scale-Revised (IES-R) of exposed group	It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome	immediately after the frontline workers come back to Xi'an
Primary	The Impact of Event Scale-Revised (IES-R) of exposed group	It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome	immediately after the frontline workers isolated for two weeks
Primary	The Impact of Event Scale-Revised (IES-R) of exposed group	It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome	immediately after the frontline workers going back to normal work for one month
Primary	The Impact of Event Scale-Revised (IES-R) of non-exposed group	It's a self-report measure assessing subjective distress resulting from a traumatic life event, with a total score of 0-88. Higher score means a worse outcome	During the procedure of collecting faecal samples from non-exposed group
Secondary	The 15-item Patient Health Questionnaire (PHQ-15) of exposed group	It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.	immediately after the frontline workers come back to Xi'an
Secondary	The 15-item Patient Health Questionnaire (PHQ-15) of exposed group	It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.	immediately after the frontline workers isolated for two weeks
Secondary	The 15-item Patient Health Questionnaire (PHQ-15) of exposed group	It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.	immediately after the frontline workers going back to normal work for one month
Secondary	The 15-item Patient Health Questionnaire-15 (PHQ-15) of non-exposed group	It's a self-administered measure assessing subjective common mental health with a total score of 0-30. Higher score means a worse outcome.	During the procedure of collecting faecal samples from non-exposed group
Secondary	The 9-item Patient Health Questionnaire (PHQ-9) of exposed group	It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.	immediately after the frontline workers come back to Xi'an
Secondary	The 9-item Patient Health Questionnaire (PHQ-9) of exposed group	It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.	immediately after the frontline workers isolated for two weeks
Secondary	The 9-item Patient Health Questionnaire (PHQ-9) of exposed group	It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.	immediately after the frontline workers going back to normal work for one month
Secondary	The 9-item Patient Health Questionnaire (PHQ-9) of non-exposed group	It's a self-report measure widely used for major depression screening with a total score of 0-27. Higher score means a worse outcome.	During the procedure of collecting faecal samples from non-exposed group
Secondary	The 7-item Generalized Anxiety Disorder Scale (GAD-7) of exposed group	It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.	immediately after the frontline workers come back to Xi'an
Secondary	The 7-item Generalized Anxiety Disorder Scale (GAD-7) of exposed group	It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.	immediately after the frontline workers isolated for two weeks
Secondary	The 7-item Generalized Anxiety Disorder Scale (GAD-7) of exposed group	It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.	immediately after the frontline workers going back to normal work for one month
Secondary	The 7-item Generalized Anxiety Disorder Scale (GAD-7) of non-exposed group	It is a practical self-report anxiety questionnaire with a total score of 0-21. Higher score means a worse outcome.	During the procedure of collecting faecal samples from non-exposed group
Secondary	The Pittsburgh Sleep Quality Index (PSQI) of exposed group	It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome	immediately after the frontline workers come back to Xi'an
Secondary	The Pittsburgh Sleep Quality Index (PSQI) of exposed group	It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome	immediately after the frontline workers isolated for two weeks
Secondary	The Pittsburgh Sleep Quality Index (PSQI) of exposed group	It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome	immediately after the frontline workers going back to normal work for one month
Secondary	The Pittsburgh Sleep Quality Index (PSQI) of non-exposed group	It is a self-report questionnaire that is widely used to assess several dimensions of sleep with a total score of 0-21. Higher score means a worse outcome	During the procedure of collecting faecal samples from non-exposed group
Secondary	The Symptom Check List 90 (SCL-90) of exposed group	It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.	immediately after the frontline workers come back to Xi'an
Secondary	The Symptom Check List 90 (SCL-90) of exposed group	It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.	immediately after the frontline workers isolated for two weeks
Secondary	The Symptom Check List 90 (SCL-90) of exposed group	It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.	immediately after the frontline workers going back to normal work for one month
Secondary	The Symptom Check List 90 (SCL-90) of non-exposed group	It is a self-report instrument widely used to measure clinical psychiatric symptoms and mental health status, with a total score of 0-360. Higher means a worse outcome.	During the procedure of collecting faecal samples from non-exposed group