Post-Traumatic Stress Disorder (PTSD) is a psychological shadow that cannot be erased or difficult to erase after experiencing or witnessing a serious traumatic event. These traumatic events can include war, natural disasters, serious accidents, violent incidents, or other situations that have a significant impact on individuals.
PTSD is not a rare problem, with 70% of people experiencing at least one traumatic event in their lifetime. The lifetime prevalence of PTSD in the population is 6%, 7% in women, and 4% in men.
People with PTSD may experience intrusive memories (repeated recall of traumatic events, nightmares, or flashbacks), heightened alertness and exaggerated reactions (being very alert, easily startled, having difficulty concentrating or sleeping, feeling constantly in danger), avoiding places/people/activities related to the traumatic event, being in a state of sustained negative emotions (such as sadness, anger, fear, or guilt), difficulty experiencing positive emotions, and various other symptoms, which is what people often refer to as being unable to escape the shadow of the event, significantly impacting daily life.
In the first two articles, Food & Mind introduced the important role of the gut microbiota in fear learning (distinguishing danger) and fear memory extinction. When fear-related abilities deteriorate to the extent of a psychological disorder (PTSD), how much can the gut microbiota play a role?
This issue of Food & Mind summarizes some of the latest research, introducing the association between PTSD and the gut microbiota, providing more choices for those troubled by this issue to move out of the shadow.
1. Association between PTSD and Gut Microbiota and Inflammation
Article: Exploring the interplay between posttraumatic stress disorder, gut microbiota, and inflammatory biomarkers: a comprehensive meta-analysis
Journal: Front Immunol
Date: February 2024
This study conducted a meta-analysis of human PTSD studies before December 1, 2023, and finally included 15 relevant studies. The results revealed:
Previous studies have found increased levels of various inflammatory markers in PTSD patients, but the meta-analysis found that only the increase in TNF-α and IL-6 reached a marginally significant level.
The association of inflammatory markers with the severity of PTSD. One study found that combat-exposed subjects with PTSD had significantly higher pro-inflammatory scores than those without PTSD. In one study, TNF-α was positively correlated with the total (frequency and intensity) PTSD symptom cluster of re-experiencing, avoidance, and hyperarousal, and the total PTSD symptom score. IL-1β was positively correlated with anxiety and depression symptoms. IL-4 was negatively correlated with total hyperarousal symptoms and systolic blood pressure. In another study, biomarkers white blood cell count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were identified as important predictors of PTSD severity.
The gut microbiota of PTSD patients has changed, but there is controversy over the specific composition of the microbiota.
This study emphasizes the significant role of inflammation and dysbiosis in PTSD, but further research is needed to understand the specific effects.
2. Repeated Social Defeat Can Induce PTSD by Disrupting the Intestinal Barrier
Article: Repeated Social Defeat Stress Induces an Inflammatory Gut Milieu by Altering the Mucosal Barrier Integrity and Gut Microbiota Homeostasis
Journal: Biol Psychiatry Glob Open Sci
Date: October 2023
This study used the Repeated Social Defeat Stress (RSDS) model in mice, which is a common animal model for PTSD. Experimental mice were repeatedly exposed to highly aggressive and larger unfamiliar mice, causing them to exhibit symptoms similar to human PTSD after multiple experiences of social defeat (being attacked, chased, threatened, etc.), including anxiety, depression, social avoidance, and enhanced stress responses.
The study found:
Compared to the control group, the gut microbiota of the model group mice changed significantly, with an increase in Firmicutes abundance and a decrease in Bacteroidetes abundance.
The inflammation levels in the colon and ileum of the model group mice increased, with increased immune cell infiltration.
The levels of antimicrobial peptides secreted by intestinal epithelial cells (such as Reg-3β and α-defensin) and lysozyme in the model group mice increased.
The expression of colonic tight junction protein claudin-2 in the model group mice changed, leading to increased epithelial permeability.
This study suggests that trauma (repeated social defeat) can induce PTSD by altering the microbiota, disrupting the intestinal barrier, causing intestinal leakage and inflammation.
3. Psychological Problems after Trauma Requiring Emergency Treatment and their Association with Gut Microbiota
Article: Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure
Journal: Transl Psychiatry
Date: November 2023
This study recruited 106 participants from the emergency department, collected fecal microbiota samples from these participants, and tracked their psychological and physical conditions (PTSD, depression scales, concussion questionnaires, etc.) 2, 8, and 12 weeks later. The analysis of the association between microbiota and these manifestations revealed:
The most common types of trauma were motor vehicle collisions (55%), falls from a height (18%), and other accidents or intentional/non-consensual events (9.8%).
The psychological and physical sequelae of the participants were significantly associated with the microbiota. The abundance of the Firmicutes bacterial CAG:555, Bifidobacterium adolescentis, and pro-inflammatory Streptococcus infantarius was associated with the severity of PTSD symptoms. The abundance of Bifidobacterium adolescentis was also associated with the severity of depression symptoms. The abundance of Methanobrevibacter smithii and Streptococcus salivarius was associated with the severity of physical symptoms.
Intestinal bacteria can predict subsequent psychological and physical symptoms. Among multiple predictor factors for PTSD, depression, and physical symptoms, Bifidobacterium adolescentis, Bifidobacterium longum, and Flavonifractor plautii ranked in the top 5 for predicting these three symptoms. Additionally, Bifidobacterium bifidum ranked third in the PTSD prediction rankings, with Bifidobacterium adolescentis and Bifidobacterium longum taking the first and second spots. Specific bacteria belonging to Methanobrevibacter and Alistipes could also predict PTSD.
Metabolic pathway analysis showed that the amino acid biosynthesis pathway was a major predictor for the three symptoms, with the L-glutamine biosynthesis pathway ranking in the top two for all symptoms. The superpathway of arginine and polyamine biosynthesis was the primary predictor for PTSD symptoms and ranked third for the depression model, showing a negative correlation with PTSD and depression scores. The top three predictive pathways all involved the metabolism of arginine, ornithine, and glutamine, three amino acids that are often interconverted. An increase in L-glutamine biosynthesis was associated with more severe PTSD, depression, and physical symptoms.
This study suggests that the gut microbiota altered by trauma can predict the risk of subsequent PTSD and depression, with high levels of various Bifidobacterium and Methanobrevibacter and an increase in L-glutamine biosynthesis implying a higher risk of PTSD and depression.
It is important to note: Bifidobacterium adolescentis, Bifidobacterium longum, and Bifidobacterium bifidum, which have always been considered representative probiotics, seem to have a negative impact on post-traumatic psychological problems, indicating that they should not be used as probiotics for PTSD intervention.
For the association of a certain factor with a disease, many people only believe in causality. So, is there a causal relationship between PTSD and abnormal microbiota? Due to the diverse and vast number of gut microbiota, it is not possible to determine the causal relationship between the microbiota and the disease as with traditional pathogenic bacteria using Koch’s postulates. However, Mendelian randomization studies also help to understand the nature of the problem.
4. Causal Association between PTSD and Abnormal Microbiota
Article: Potential causal association between gut microbiome and posttraumatic stress disorder
Journal: Transl Psychiatry
Date: January 2024
Mendelian Randomization (MR) is a statistical method used to study causal relationships. It uses genetic variations as instrumental variables to assess the causal effects of environmental factors (such as lifestyle, dietary habits) on disease risk.
The main principle of MR is: firstly, identify genetic variations strongly associated with specific exposure factors (such as weight, alcohol consumption); then, study the relationship between these exposure factors and the target disease (such as heart disease, diabetes); finally, infer the causal effects of exposure factors on the disease through the relationship between genetic variation-exposure factor-disease.
The advantage of MR is that it can reduce the interference of confounding factors and reverse causal effects of the disease on exposure factors. The disadvantage is that thousands of samples are required to detect significant causal relationships.
This study mainly used two datasets: the Freeze 2 dataset (which includes 23,212 cases of PTSD and 151,447 controls) and the FinnGen dataset (which includes 2,100 cases and 307,558 controls). The results showed:
Analysis of the Freeze 2 dataset revealed a causal association between PTSD and gut microbiota. Instrumental variable analysis confirmed potential causal relationships between 8 specific microbial traits and PTSD. The Porphyromonadaceae, Veillonellaceae, Dorea, Gordonibacter, Sellimonas, and Clostridiales reduced the risk of PTSD. However, in further sensitivity analysis, these associations were no longer significant.
Analysis of the FinnGen dataset also confirmed the association between PTSD and gut microbiota. Instrumental variable analysis also confirmed potential causal relationships between 8 microbial traits and PTSD. However, in further sensitivity analysis, these associations were no longer significant.
These results indicate that PTSD does indeed have a causal relationship with the gut microbiota, but further research is needed to understand which specific microorganisms play a key role. Both datasets found that Dorea and Sellimonas may help suppress the occurrence and development of PTSD.
Food & Mind Warm Summary: Whether a person will develop PTSD and depression after an unfortunate event, in addition to social support, economic conditions, and cognitive methods, the individual’s gut microbiota is also an important factor not to be overlooked. Whether it is a major natural disaster, social defeat, or PTSD induced by physical damage, gut microbiota plays a role, and perhaps changes in microbiota before and after the event can predict the likelihood of psychological problems afterwards.
Abnormal microbiota can reduce the level of intestinal barrier, increase the baseline inflammation level, alter the brain’s fear neural network, reduce fear learning ability (correctly distinguishing what is dangerous and what is not), impair fear extinction ability (forgetting about fearful events), and increase the risk of PTSD.
In contrast, a healthy microbiota helps enhance psychological resilience (tolerance and resistance to trauma), allowing individuals to recover more quickly from physical or psychological trauma, suffer less from PTSD and depression torment.
Compared to social support, economic conditions, and cognitive methods, the gut microbiota is a more controllable factor and one that we can regulate ourselves. Many people say they should love themselves, but they don’t know how. In fact, a healthy diet, regular exercise, proper rest, and shaping a balanced and diverse microbiota are the best ways to love oneself.
No one knows when an accident will happen to them, but cultivating a healthy microbiota can help individuals better weather infections (such as the flu or COVID-19) or the challenges of misfortune (such as traumatic events), withstand any life setbacks, and live a happier life.
