Study Identifies Link Between Post-Traumatic Stress Disorder and Gut Microbiome Composition in a Cohort of Women

  • A study published in Nature Mental Health examined the links between post-traumatic stress disorder (PTSD), dietary patterns, and gut microbiome in U.S. nurses
  • Results showed that nurses with higher PTSD symptom levels tended to eat less plant-based food and more red/processed meat
  • Microbial processes related to the production of pantothenate and coenzyme A can potentially be protective against PTSD

When we are exposed to distressing events or conditions that overwhelm our ability to cope, our body can produce a severe emotional response, and we experience psychological trauma. We feel that we have lost control of events around us. Our ability to integrate these emotional experiences into the story of our lives is reduced. After experiencing psychological trauma, people often start dividing the subjective timeline of their lives into the time before and the time after the traumatic event. Long-lasting psychological and health consequences may often follow (Hamburger et al., 2021). Among other things, the experience of psychological trauma can lead to the development of a serious mental health disorder called post-traumatic stress disorder or PTSD.

 

After experiencing psychological trauma, people often start dividing the subjective timeline of their lives into the time before and after the traumatic event 

 

What is post-traumatic stress disorder?
Post-traumatic stress disorder is a mental health condition that can develop in individuals who have experienced or witnessed a traumatic event. Symptoms of PTSD include intrusive thoughts, nightmares, and flashbacks related to the traumatic experience, causing significant distress. Individuals with PTSD may actively avoid reminders of the trauma, experience heightened arousal, and have negative changes in mood and cognition.

Mainstream treatments for PTSD include psychotherapy, particularly cognitive-behavioral psychotherapy, and medications. Studies indicate that these treatments can be effective in reducing PTSD symptoms (see Figure 1). In some individuals, they are very effective (Watts et al., 2013). However, around 20% of patients suffering from PTSD drop out of treatment before symptoms have withdrawn, while up to 60% of individuals undergoing treatment do not respond to it, i.e., experience no reduction of symptoms as a result (Wittmann et al., 2021).

 

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Figure 1. PTSD symptoms and mainstream treatments 

 

For these reasons, researchers are intensely working on new treatment options. They are trying alternative ways to achieve a reduction of symptoms, such as acupuncture (Watts et al., 2013) or psychedelic drugs (Barone et al., 2019). Researchers are also looking at chemicals that could potentially prevent the disorder from forming in the first place if taken immediately after the traumatic event, such as hydrocortisone (Hennessy et al., 2022).

Health impact of PTSD
Individuals suffering from PTSD often suffer from other psychiatric disorders as well. Epidemiological surveys indicate that the vast majority of individuals with PTSD meet the criteria for at least one other disorder, while a substantial percentage have three or more other psychiatric disorders. These most commonly include major depressive disorder, substance use disorder, and anxiety disorders (Brady et al., 2000).

 

The majority of individuals with PTSD meet the criteria for at least one other disorder, while a substantial percentage have three or more other psychiatric disorders

 

Individuals with PTSD also have a higher likelihood of various somatic diseases, particularly chronic ones. These include asthma, cardiovascular disease, chronic pain and inflammation, obesity, type 2 diabetes, gastrointestinal disorders, and cognitive decline (Ke et al., 2023).

However, researchers are still looking for mechanisms through which this association between PTSD and somatic disorders is achieved. One promising avenue of research is the study of the gut microbiome, the community of organisms living in the human digestive system. The recent discovery of the microbiota-gut-brain axis, a bidirectional communication pathway through which gut microorganisms affect processes in the brain and vice versa (Carbia et al., 2023; García-Cabrerizo et al., 2021), has made it even more likely that at least a part of the link between PTSD and somatic disorder includes the gut microbiome.

 

Researchers are looking for mechanisms connecting PTSD and somatic disorders -with one promising avenue of research being the gut microbiome

 

The current study
Study author Shanlin Ke and his colleagues hypothesized that gut microbiome might play a role in PTSD. They note that previous studies have already linked the gut microbiome with various other mental health disorders through the microbiota-gut-brain axis (Hedrih, 2023; Leclercq et al., 2020; Valles-Colomer et al., 2019). Additionally, studies show that the gut microbiome influences the brain region involved in learned fear. Fear is a key feature of PTSD. Gut microbiota depends on food intake, while individuals with PTSD tend to be more prone to eating unhealthy foods (Ke et al., 2023).

 

Previous studies have already linked the gut microbiome with various other mental health disorders through the microbiota-gut-brain axis (MGBA)

 

With this in mind, these researchers analyzed data from two studies of female registered nurses in the U.S. in order to systematically examine the associations of trauma exposure and PTSD status with dietary and microbiome data.

The study procedure
Data came from 191 nurses who were part of the NHS-II study. NHS-II is a large longitudinal study of U.S. women with over 100,000 registered nurses that started in 1989. Nurses whose data were analyzed here participated in two substudies – the 2008 PTSD substudy that collected data about trauma exposure and PTSD symptoms and the 2013 mind-body study that, among other things, collected up to four stool samples. Stool samples were collected 48-72 hours apart. This was followed by a second set of collections six months later. Stool samples were analyzed to make inferences about the composition of the gut microbiome.

Of the nurses included in this study, 44 had probable PTSD, 119 were exposed to trauma but did not develop PTSD, and 28 participants had no trauma exposure (see Figure 2).

 

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Figure 2. Study Procedure

 

No association between PTSD and overall microbiome structure
Statistical analyses showed no associations between overall gut microbiota composition and PTSD status. Gut microbiota diversity was also not associated with PTSD.

However, there were associations between various other factors and the overall microbiome structure. Body mass index, depression, and the use of antidepressants were all associated with the overall composition of gut microbiome species.

Childhood trauma experiences and antidepressant use were associated with the relative abundance of species forming different metabolic pathways. The gut microbiome metabolic pathways refer to types of activities within the gastrointestinal tract that specific species of microorganisms perform.

Individuals with PTSD eat less plant-based food and more red/processed meat
Examination of associations between dietary habits and PTSD revealed that individuals with more pronounced PTSD symptoms tend to eat less plant-based foods and more red/processed meats compared to individuals with lower PTSD symptom levels. The diets of these individuals were less healthy overall. 

 

Individuals with more pronounced PTSD symptoms tend to eat less plant-based foods and more red/processed meats compared to individuals with less PTSD symptoms 

 

Individuals with PTSD symptoms had lower abundances of Eubacterium eligens
After statistical analyses showed no associations between the overall gut microbiome composition and PTSD, these authors examined associations between PTSD symptoms and the abundance of individual species of bacteria. They looked for species of microorganisms that differed in abundance in individuals with different levels of PTSD symptoms. Three species were clearly more abundant in individuals with more PTSD symptoms – Parabacteroides goldsteinii, Barnesiella intestinihominis, and Paraprevotella unclassified. Seven species with the highest negative association with PTSD symptoms, i.e., species less abundant in individuals with more PTSD symptoms, were also identified (Eubacterium eligens, Parabacteroides distasonis, Akkermansia muciniphila, Bacteroides massiliensis, Bifidobacterium longum, Dialister invisus, and Roseburia inulinivorans). These species play diverse roles in the human digestive system, contributing to functions ranging from fermentation of dietary fibers to protection of the gut lining.

Eubacterium eligens (a good bacteria) was less abundant in individuals eating more pies, carbonated beverages with sugars, candy without chocolate, hot dogs, bacon, and processed meats. It tended to be more abundant in individuals eating more vegetables (for example, raw carrot, spinach/collard greens cooked, and yellow squash), fruits (for example, orange and banana), and fish. The abundance of this bacteria was the most strongly associated with PTSD symptoms of all analyzed microorganisms. Eubacterium eligens in the gut synthesize pantothenate and Coenzyme A (see Figure 3).

 

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Figure 3. Microorganisms associated with PTSD

 

Researchers tested a number of statistical models proposing that specific dietary habits mediate the impact of PTSD symptoms on the abundance of specific species of gut bacteria. These analyses revealed that it is possible that the impact of PTSD symptoms on the abundance of Eubacterium eligens is mediated by the consumption of raw carrots. Similarly, it is possible that Adlercreutzia equolifaciens mediates the link between PTSD symptoms and the intake of dairy-cottage/ricotta cheese.

Conclusion
In summary, the study showed that PTSD symptoms in U.S. nurses are not associated with the overall structure of the gut microbiome, but the abundance of several bacterial species was associated with the severity of PTSD symptoms in spite of this. Additionally, it turned out that participants with PTSD tend to eat less plant-based food and more red/processed meat. Their overall dietary habits tended to be less healthy (see Figure 4). 

 

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Figure 4. Research findings (Ke et al., 2023)

 

The study also established statistical links between PTSD symptoms, dietary habits, and bacteria. Future studies could explore the nature of these links in more detail. Potentially, these could lead to the discovery of ways to affect PTSD symptoms through dietary interventions and modifying the abundance of certain species of gut bacteria. However, the feasibility of such an approach is yet to be established.

The paper “Association of probable post-traumatic stress disorder with dietary pattern and gut microbiome in a cohort of women” was authored by Shanlin Ke, Xu-Wen Wang, Andrew Ratanatharathorn, Tianyi Huang, Andrea L. Roberts, Francine Grodstein, Laura D. Kubzansky, Karestan C. Koenen, and Yang-Yu Liu.

Visit the research category within the Nutritional Psychology Research Library on “Diet, Trauma and PTSD” to learn more about the connection between diet and trauma. To access evidence-based continuing education on the connection between the microbiome and mental health, see the CNP Education page.

 

References

Barone, W., Beck, J., Mitsunaga-Whitten, M., & Perl, P. (2019). Perceived Benefits of MDMA-Assisted Psychotherapy beyond Symptom Reduction: Qualitative Follow-Up Study of a Clinical Trial for Individuals with Treatment-Resistant PTSD. Journal of Psychoactive Drugs, 51(2), 199–208. https://doi.org/10.1080/02791072.2019.1580805

Brady, K., Killeen, T., Brewerton, T., & Lucerini, S. (2000). Comorbidity of Psychiatric Disorders and Posttraumatic Stress Disorder. Journal of Clinical Psychiatry, 61(suppl 7), 22–32.

Carbia, C., Bastiaanssen, T. F. S., Iannone, F., García-cabrerizo, R., Boscaini, S., Berding, K., Strain, C. R., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2023). The Microbiome-Gut-Brain axis regulates social cognition & craving in young binge drinkers. EBioMedicine, 89, 104442. https://doi.org/10.1016/j.ebiom.2023.104442

García-Cabrerizo, R., Carbia, C., O´Riordan, K. J., Schellekens, H., & Cryan, J. F. (2021). Microbiota-gut-brain axis as a regulator of reward processes. Journal of Neurochemistry, 157(5), 1495–1524. https://doi.org/10.1111/JNC.15284

Hamburger, A., Hancheva, C., & Volkan, V. (Eds.). (2021). Social Trauma – An Interdisciplinary Textbook. Springer Nature Switzerland AG. https://doi.org/10.1007/978-3-030-47817-9

Hedrih, V. (2023). Women Consuming Lots of Artificially Sweetened Beverages Might Have a Higher Risk of Depression, Study Finds. CNP Articles in Nutritional Psychology. https://www.nutritional-psychology.org/women-consuming-lots-of-artificially-sweetened-beverages-might-have-a-higher-risk-of-depression-study-finds/

Hennessy, V. E., Troebinger, L., Iskandar, G., Das, R. K., & Kamboj, S. K. (2022). Accelerated forgetting of a trauma-like event in healthy men and women after a single dose of hydrocortisone. Translational Psychiatry, 12(1). https://doi.org/10.1038/s41398-022-02126-2

Ke, S., Wang, X.-W., Ratanatharathorn, A., Huang, T., Roberts, A. L., Grodstein, F., Kubzansky, L. D., Koenen, K. C., & Liu, Y.-Y. (2023). Association of probable post-traumatic stress disorder with dietary pattern and gut microbiome in a cohort of women. Nature Mental Health, 1(11), 900–913. https://doi.org/10.1038/s44220-023-00145-6

Leclercq, S., Le Roy, T., Furgiuele, S., Coste, V., Bindels, L. B., Leyrolle, Q., Neyrinck, A. M., Quoilin, C., Amadieu, C., Petit, G., Dricot, L., Tagliatti, V., Cani, P. D., Verbeke, K., Colet, J. M., Stärkel, P., de Timary, P., & Delzenne, N. M. (2020). Gut Microbiota-Induced Changes in β-Hydroxybutyrate Metabolism Are Linked to Altered Sociability and Depression in Alcohol Use Disorder. Cell Reports, 33(2). https://doi.org/10.1016/J.CELREP.2020.108238

Valles-Colomer, M., Falony, G., Darzi, Y., Tigchelaar, E. F., Wang, J., Tito, R. Y., Schiweck, C., Kurilshikov, A., Joossens, M., Wijmenga, C., Claes, S., Van Oudenhove, L., Zhernakova, A., Vieira-Silva, S., & Raes, J. (2019). The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology, 4(4), 623–632. https://doi.org/10.1038/s41564-018-0337-x

Watts, B. V., Schnurr, P. P., Mayo, L., Young-Xu, Y., Weeks, W. B., & Friedman, M. J. (2013). Meta-analysis of the efficacy of treatments for posttraumatic stress disorder. Journal of Clinical Psychiatry, 74(6). https://doi.org/10.4088/JCP.12r08225

Wittmann, L., Muller, J., Morina, N., Maercker, A., & Schnyder, U. (2021). Predicting Treatment Response in Psychotherapy for Postraumatic Stress Disorder: a Pilot Study. Psihologija, 54(1), 1–14. https://doi.org/10.2298/PSI190905007W

 

 

Can Symptoms of Alzheimer’s be Transferred to Rats via the Gut Microbiota of Alzheimer’s Patients?

  • A study published in Brain showed that symptoms of Alzheimer’s disease can be transferred to young rats via the gut microbiota of Alzheimer’s patients
  • Transplantation of these microorganisms into the guts of healthy rats induced cognitive deficits
  • The deficits resulted from the disruption of adult hippocampal neurogenesis, the capacity of the hippocampus to produce new neurons

Our gut is home to trillions of different microorganisms. These microorganisms sustain themselves using the food we eat and help our digestion process. For example, many food items contain substances called resistant starches. Our digestive system cannot digest these resistant starches, but some bacteria in our gut can. They ferment those types of starches, creating substances called short-chain fatty acids (SCFA) that our bodies can use (Li et al., 2023) (see Figure 1). 

 

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Figure 1. Digestion of resistant starch by gut bacteria

 

Similarly, these bacteria help digest substances like dietary fiber, other complex polysaccharides, lignans, and many others, converting them into substances our body can use as nutrients or that convey various health benefits. However, when pathogenic, unhealthy microorganisms infect our digestive tract, we experience an upset stomach. This includes symptoms such as nausea, vomiting, diarrhea, abdominal pain, and others.

The microbiota-gut-brain axis (MGBA)
This community of microorganisms living in our gut is called the gut microbiota. However, its effects on us go far beyond helping digestion. Gut microbiota can also influence our central nervous system –and be influenced by it. The mechanism through which this bidirectional communication link between gut microbiota and the brain is achieved is called the microbiota-gut-brain axis (MGBA). It is crucial in regulating various physiological and psychological processes (Carbia et al., 2023; García-Cabrerizo et al., 2021).

 

The Microbiota-Gut-Brain Axis is crucial in regulating various physiological and psychological processes

 

This bidirectional communication mechanism occurs via several biomolecules, including the hormone cortisol, short-chain fatty acids (SCFAs), and tryptophan. Emerging studies reveal that the gut microbiota produces substances (called ‘signaling molecules’) that can influence the brain’s activity and responses to stress and emotions (more about this can be found in NP 120 Parts I & II). The MGBA is closely tied to the immune system, influencing the body’s inflammatory responses and potentially contributing to neuroinflammation (Zhu et al., 2023) (see Figure 2).

 

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Figure 2. MGBA, bidirectional communication, and signaling molecules

 

What is Alzheimer’s disease?
Alzheimer’s disease is a progressive neurodegenerative disorder characterized by a decline in cognitive function, memory loss, and changes in behavior. It is the most common form of dementia, affecting primarily older adults. The exact cause of Alzheimer’s disease is not fully understood. Still, it is associated with the accumulation of abnormal protein deposits in the brain, called beta-amyloid plaques and tau tangles. These deposits disrupt communication between nerve cells and eventually lead to their degeneration and death (Grabrucker et al., 2023) (see Figure 3).

 

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Figure 3. Alzheimer’s Disease (AD)

 

Alzheimer’s disease and adult hippocampal neurogenesis
The hippocampus is a brain area that is particularly vulnerable to Alzheimer’s disease. It plays a crucial role in learning, memory, and emotional regulation. The hippocampus hosts a population of neural stem cells, special undifferentiated cells that can produce new neurons throughout their lifespan. This process of creating new neural cells is called adult hippocampal neurogenesis. It is crucial for cognitive processes like spatial learning, distinguishing between similar events and environments, and emotion regulation (see Figure 4).

 

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Figure 4. Adult hippocampal neurogenesis

 

Interestingly, hippocampal neurogenesis is impaired in Alzheimer’s even before abnormal protein deposits can be detected in the brain, including in the hippocampus. This indicates that dysfunction of this system is an early indicator that Alzheimer’s disease is developing (Grabrucker et al., 2023).

 

The hippocampus is a brain area that is particularly vulnerable to Alzheimer’s disease. It plays a crucial role in learning, memory, and emotional regulation

 

Causes of Alzheimer’s
Genetic factors, such as specific gene mutations, are linked to early-onset Alzheimer’s, while other risk factors include age, family history, and certain lifestyle factors. Despite ongoing research, there is currently no cure for Alzheimer’s disease, and treatment focuses on managing symptoms and improving the quality of life for affected individuals.

However, the recent discovery of the MGBA has opened a new avenue of research demonstrating that this communication pathway is a significant mediator of behavior throughout the lifespan. Studies indicate clear links between gut microbiota composition and behavior (e.g., Leclercq et al., 2020; Valles-Colomer et al., 2019).

 

Studies indicate clear links between gut microbiota composition and behavior

 

Recently, links between the MGBA and Alzheimer’s have begun to appear. Studies on mice indicate that transplanting gut microbiota from Alzheimer’s patients into mice can cause adverse cognitive changes in these mice (Kim et al., 2021; Wang et al., 2022) (see Figure 5). But could it also disrupt the adult hippocampal neurogenesis? And would these changes correlate with the level of cognitive impairment of the person the transplanted microbiota came from?

 

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Figure 5. Gut microbiota transplanted from Alzheimer’s patients 

 

The current study
Current studies clearly implicate the gut microbiota in the pathological features of Alzheimer’s disease, but until this particular study, it has remained unclear whether cognitive symptoms in human Alzheimer’s patients and underlying cellular changes (such as the disruption of adult hippocampal neurogenesis) could be transmitted to a healthy organism via the gut microbiota. Study author Stefanie Grabrucker and her colleagues wanted to find out. They also wanted to uncover the mechanism through which this happens.

These authors conducted a study in which they took fecal samples containing gut microbiota from humans suffering from Alzheimer’s disease and transplanted them into the guts of young adult male rats.

 

Current studies implicate gut microbiota in the pathological features of AD, but until now, it has remained unclear whether cognitive symptoms and underlying cellular changes in human Alzheimer’s patients could be transmitted to a healthy organism via the gut microbiota

 

The study procedure
Study participants were 69 patients with Alzheimer’s disease, and 64 healthy individuals were included as controls. They were recruited at the IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. They all underwent clinical assessment for cognitive function and a physical examination. All participants gave blood samples for further analysis. Fifty-four participants with Alzheimer’s disease and 41 healthy participants gave stool samples in a sterile cup at their homes. Researchers processed these samples for transplanting gut microbiota found in feces into rats.

Animals used in the study were male Sprague-Dawley rats aged 11 weeks. They were kept in environmentally controlled conditions at a temperature of 21oC and under a 12-hour light-dark cycle (12 hours in light and 12 hours in the dark).

Transplanting gut microbiota from stool samples into rats
Researchers kept rats for two weeks after arrival at the laboratory without any treatment to let them acclimatize. After this period, they added a powerful cocktail of antibiotics to their water for seven consecutive days. This combination of antibiotics consisted of ampicillin (1 g/l), vancomycin (500 mg/l), ciprofloxacin HCL (200 mg/l), and imipenem (250 mg/l). This treatment aimed to deplete rats’ own microbiota so that their digestive system could readily accept the microorganisms to be transplanted from human participants.

After the antibiotic treatment, the study authors randomly allocated the rats into two groups. one was to receive microbiota transplants from Alzheimer’s patients, while the other would receive it from healthy control participants.

They then applied oral gavage of homogenized fecal slurry of human participants (from stool samples) on them for three days. Gavage is a force-feeding method involving inserting a tube into the animal’s esophagus and delivering a measured amount of food directly into the stomach. In this way, study authors transplanted the gut microbiota of human study participants into the guts of these rats (see Figure 6).

Behavior testing and other analyses
Ten days after transplanting the gut microbiota to rats, these researchers conducted a series of behavioral tests on the rats. They conducted the tests during the day (i.e., light cycle), between 9:00 and 19:00. There was a minimum interval of 36 hours between behavioral tests. The tests used were Open Field, Elevated Plus Maze, Modified Spontaneous Location Recognition Test, Novel Object Recognition, Novel Location Recognition, Morris Water Maze, and Forced Swim Test. Their goal was to examine the rats’ cognitive capacity.

Study authors also collected and analyzed fecal samples of the rats during the study. They took blood from their tails ten days after microbiota transplantation for analysis. At the end of the study, the rats were killed, and additional analyses were done on their brain tissue and blood from the trunk (see Figure 6).

 

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Figure 6. Research procedure

 

Microbiota composition differed between Alzheimer’s patients and controls
Researchers used metagenomics (bacterial 16S rRNA gene sequencing) on participants’ stool samples to estimate the composition of participants’ gut microbiota. Results revealed no differences in microbiota diversity between participants with and without Alzheimer’s.

However, there were differences in the abundances of specific groups of bacterial species. Alzheimer’s patients had a higher abundance of Bacteroides (particularly of various species associated with inflammatory processes) and Desulfovibrio genera of bacteria. They had lower abundances of Clostridium sensu stricto 1 and the short-chain fatty acid butyrate-producing genera Coprococcus.

Further analyses revealed that participants with Alzheimer’s who had better cognitive function and higher mental clarity (assessed using the Mini-Mental State Examination) tended to have higher abundances of Coproccocus bacteria. These individuals tended to have lower abundances of Desulfovibrio and Dialister species of bacteria.

Gut microbiota from Alzheimer’s patients induced cognitive deficits in rats
Analyses of rat stool samples indicated that gut microbiota transplantation was successful. Comparing rats with microbiota from healthy human participants and those from Alzheimer’s patients, study authors noted that the fecal matter of rats with microbiota from Alzheimer’s patients had higher water content. These rats also increased their water intake, and their colon length decreased. There were other structural changes in the colons of these rats as well.

Behavioral tests showed no changes in rats that received microbiota transplants from healthy human participants. On the other hand, rats with microbiota from Alzheimer’s patients showed impaired ability to recognize familiar locations. They also showed impairment in tasks that relied on different types of memory. Study authors note that all of these cognitive functions depend on the normal functioning of hippocampal neurogenesis.

 

Rats with microbiota from Alzheimer’s patients showed an impaired ability to recognize familiar locations

 

Hippocampal neurogenesis was reduced in rats with microbiota from Alzheimer’s patients
Direct assessment of hippocampal neurogenesis in rats that received gut microbiota from Alzheimer’s patients showed that hippocampal neurogenesis was indeed disrupted, confirming the study authors’ suspicions. These rats had substantially fewer new neurons than those that received microbiota from healthy human participants.

Serum of patients with Alzheimer’s reduced the capacity of human brain cells to multiply
The study authors then conducted an in vitro experiment on embryonic human hippocampal progenitor cells (undifferentiated cells found in the hippocampus of the brain, obtained from female human fetuses that were medically terminated). After treating these cells with serum (the liquid component of blood that remains after blood coagulation) taken from the two groups of human study participants, researchers noted that the serum from Alzheimer’s patients decreased the capacity of these cells to multiply.

The capacity of these cells to multiply after treatment depended on the human participant serum from which they came. More specifically, the capacity of these cells to multiply tended to be better after treatment with serum from Alzheimer’s patients with better cognitive functions. The prevalence of indicators of neuron development was higher if serum from Alzheimer’s patients with better cognitive function assessments was used.

Conclusion
The study showed that it is possible to transfer symptoms of Alzheimer’s disease to young, healthy rats by using the gut microbiota of humans suffering from Alzheimer’s disease. This transfer induced a number of changes in the digestive tract and disrupted cognitive functions that depend on preserved hippocampal neurogenesis -–the capacity of stem cells in the hippocampus to generate new neurons (see Figure 7).

 

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Figure 7. Transfer of AD symptoms via gut microbiota

 

These results demonstrate that gut microbiota has a causal role in Alzheimer’s disease and that adult hippocampal neurogenesis is central for cognitive impairments in its course. But most importantly, they indicate that Alzheimer’s disease can potentially be transmitted through the fecal-oral route. These findings will likely lead to new ways to prevent and possibly even treat Alzheimer’s disease very soon.

The paper “Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis” was authored by Stefanie Grabrucker, Moira Marizzoni, Edina Silajdžić, Nicola Lopizzo, Elisa Mombelli, Sarah Nicolas, Sebastian Dohm-Hansen, Catia Scassellati, Davide Vito Moretti, Melissa Rosa, Karina Hoffmann, John F. Cryan, Olivia F. O’Leary, Jane A. English, Aonghus Lavelle, Cora O’Neill, Sandrine Thuret, Annamaria Cattaneo, and Yvonne M. Nolan.

 

References

Carbia, C., Bastiaanssen, T. F. S., Iannone, F., García-cabrerizo, R., Boscaini, S., Berding, K., Strain, C. R., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2023). The Microbiome-Gut-Brain axis regulates social cognition & craving in young binge drinkers. EBioMedicine, 89, 104442. https://doi.org/10.1016/j.ebiom.2023.104442

García-Cabrerizo, R., Carbia, C., O´Riordan, K. J., Schellekens, H., & Cryan, J. F. (2021). Microbiota-gut-brain axis as a regulator of reward processes. Journal of Neurochemistry, 157(5), 1495–1524. https://doi.org/10.1111/JNC.15284

Grabrucker, S., Marizzoni, M., Silajdžić, E., Lopizzo, N., Mombelli, E., Nicolas, S., Dohm-Hansen, S., Scassellati, C., Moretti, D. V., Rosa, M., Hoffmann, K., Cryan, J. F., O’Leary, O. F., English, J. A., Lavelle, A., O’Neill, C., Thuret, S., Cattaneo, A., & Nolan, Y. M. (2023). Microbiota from Alzheimer’s patients induce deficits in cognition and hippocampal neurogenesis. Brain. https://doi.org/10.1093/brain/awad303

Kim, N., Jeon, S. H., Ju, I. G., Gee, M. S., Do, J., Oh, M. S., & Lee, J. K. (2021). Transplantation of gut microbiota derived from Alzheimer’s disease mouse model impairs memory function and neurogenesis in C57BL/6 mice. Brain, Behavior, and Immunity, 98, 357–365. https://doi.org/10.1016/J.BBI.2021.09.002

Leclercq, S., Le Roy, T., Furgiuele, S., Coste, V., Bindels, L. B., Leyrolle, Q., Neyrinck, A. M., Quoilin, C., Amadieu, C., Petit, G., Dricot, L., Tagliatti, V., Cani, P. D., Verbeke, K., Colet, J. M., Stärkel, P., de Timary, P., & Delzenne, N. M. (2020). Gut Microbiota-Induced Changes in β-Hydroxybutyrate Metabolism Are Linked to Altered Sociability and Depression in Alcohol Use Disorder. Cell Reports, 33(2). https://doi.org/10.1016/J.CELREP.2020.108238

Li, C., Hu, Y., Li, S., Yi, X., Shao, S., Yu, W., & Li, E. (2023). Biological factors controlling starch digestibility in human digestive system. In Food Science and Human Wellness (Vol. 12, Issue 2, pp. 351–358). KeAi Communications Co. https://doi.org/10.1016/j.fshw.2022.07.037

Valles-Colomer, M., Falony, G., Darzi, Y., Tigchelaar, E. F., Wang, J., Tito, R. Y., Schiweck, C., Kurilshikov, A., Joossens, M., Wijmenga, C., Claes, S., Van Oudenhove, L., Zhernakova, A., Vieira-Silva, S., & Raes, J. (2019). The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology, 4(4), 623–632. https://doi.org/10.1038/s41564-018-0337-x

Wang, F., Gu, Y., Xu, C., Du, K., Zhao, C., Zhao, Y., & Liu, X. (2022). Transplantation of fecal microbiota from APP/PS1 mice and Alzheimer’s disease patients enhanced endoplasmic reticulum stress in the cerebral cortex of wild-type mice. Frontiers in Aging Neuroscience, 14. https://doi.org/10.3389/fnagi.2022.858130

Zhu, X., Sakamoto, S., Ishii, C., Smith, M. D., Ito, K., Obayashi, M., Unger, L., Hasegawa, Y., Kurokawa, S., Kishimoto, T., Li, H., Hatano, S., Wang, T. H., Yoshikai, Y., Kano, S. ichi, Fukuda, S., Sanada, K., Calabresi, P. A., & Kamiya, A. (2023). Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses. Nature Immunology. https://doi.org/10.1038/s41590-023-01447-8

 

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