According to a Chinese study on teenagers, bacteria are not the only gut microbes involved in depression. Microscopic fungi found in the colon could also be responsible.
Is depression linked to the microscopic fungi that populate the gut alongside bacteria and viruses?
So suggests a study on adolescent patients, the results of which have recently been published in the Journal of Affective Disorders1, further proof for the existence of a gut-brain axis.
Gut fungi of 300 teenagers have been closely examined
To this end, Chinese researchers recruited 145 teenagers aged between 12 and 18 years who suffered from depression. They collected 2 g of stool from each teenager and analyzed the fungal (i.e., the mycobiota) and bacterial composition of their gut microbiota. They then compared these analyses to those of the stools of 110 children with no mental health problems.
The results?
Firstly, there were significant differences in mycobiota composition between the teens who suffered from depression and those who did not.
Nearly half of Europeans are unaware that the microbiota contains fungi
So you didn’t know that, as well as bacteria and viruses, the microbiota contains fungi? Don’t feel bad, you certainly aren’t alone! According to the results of the International Microbiota Observatory, a major survey by Ipsos involving 6,500 people across seven countries, almost half of Europeans (46%) are unaware that the microbiota contains bacteria, fungi, and viruses. This is also the case for half of Brazilians and Chinese.
“Fungal dysbiosis”
The authors noted the existence of a “fungal (sidenote:
Dysbiosis
Generally defined as an alteration in the composition and function of the microbiota caused by a combination of environmental and individual-specific factors.
Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol. 2017;17(4):219-232.)” in the former group, with the depressed teens having more Saccharomyces and Apiotrichum than the latter group but less Aspergillus and Xeromyces. This type of dysbiosis had already been noted in children suffering from autism and Rett syndrome.
These findings are interesting because previous studies have shown that fungi can synthesize molecules that are able to reach the brain and induce depressive behavior. For example, Aspergillus can indirectly modulate inflammation of the central nervous system and modify its functioning.
The mycobiota, crucial to human health
Less abundant than bacteria (they make up a mere 0.1% of gut microorganisms), less well known and less studied, the microscopic fungi in the microbiota (i.e., the “mycobiota”) are nonetheless crucial to health.
According to a review published in 2022 in The Lancet2 :
They play an important role in regulating homeostasis and immunity;
Fungal imbalances may have an impact on certain illnesses, including inflammatory bowel disease, colorectal and pancreatic cancer, obesity, diabetes mellitus, autism, and Alzheimer’s disease;
Stable interactions with the bacteria in the microbiota appear to be a marker of good health.
Influence on the bacteria of the gut microbiota
Another finding was that in the depressed teenagers, the presence of certain fungi was associated with that of certain bacteria, suggesting a strong interaction between these two major groups of microorganisms.
Furthermore, these connections between fungal and bacterial populations were markedly different than in the healthy adolescents. We know that strong interactions between bacteria and fungi are the marker of a stable microbial ecosystem.
For example, in the gut microbiota of the depressed teenagers, the fungus Penicillium and the bacterial genus Faecalibacterium were both diminished. The bacterium Faecalibacterium prausnitzii is well known to researchers for its anti-inflammatory properties and potential anxiolytic and antidepressant effect (in animals). Conversely, the fungus Candida, known for its adverse effects on health, was positively associated with Bacteroides and Parasutterella, with this “co-presence” potentially associated with depression.
This study is the first to explore the links between the mycobiota and depression in teenagers. Although they must still be confirmed, the results open up new prospects for one day modulating the gut mycobiota (with the help of probiotics, prebiotics, antifungal drugs, fecal mycobiota transplants, etc.) to treat depression, an illness that remains poorly managed to this day.
In 2023, Danish and American clinicians published the case of a woman in her thirties with a history of late pregnancy losses and severe vaginal dysbiosis. The transplant of a healthy vaginal microbiota suppressed the dysbiosis and its symptoms. A full-term pregnancy ensued. Let’s take a closer look at this clinical case.
This case has clear scientific interest. A woman with a history of late pregnancy losses and severe vaginal dysbiosis undergoes a vaginal microbiota transplant (VMT). Five months later, she becomes pregnant, with a healthy vaginal flora, and subsequently gives birth to a full-term baby. However, the limitations of the study should be noted: it involved a single patient diagnosed with antiphospholipid antibody syndrome (APLS, a thrombophilia associated with miscarriages). Furthermore, therapy received for this APLS during her last pregnancy may explain the results in part or in full.
50%
Only one woman in two knows exactly what vaginal flora is
Vaginal dysbiosis, symptoms and recurrent miscarriages
Prior to the transplant, the 30-year-old mother of one had suffered a series of pregnancy losses, some of them late (gestational week 27 in 2019, and weeks 17 and 23 in 2020). For the previous nine years, she had complained of itching and vaginal discharge (abundant yellow/green vaginal discharge, foul odor), which worsened during her pregnancy attempts, despite treatment. With good reason: in July 2021, her vaginal microbiota showed a very strong dysbiosis, with a 91.3% dominance of Gardnerella spp. This floral composition is the opposite of a healthy vaginal microbiota, in which a few species of vaginal lactobacilli (L. crispatus, L. gasseri, L. iners or L. jensenii) should dominate. These lactobacilli produce lactic acid, which lowers vaginal pH and ensures a woman’s well-being.
According to a compassionate use protocol, a VMT from a healthy donor was performed in September 2021, on day 10 of her menstrual cycle, without antibiotic pretreatment. While orally or vaginally administered antibiotics (metronidazole or clindamycin) can have a cure rate for vaginal dysbiosis of 80%-90% one month after treatment, the recurrence rate can be as high as 60% after one year, with the added risk of resistance.
The VMT rapidly corrected the dysbiosis and its symptoms and for several months Lactobacillus strains similar to those of the donor became dominant. In February 2022, the patient became pregnant naturally. (sidenote:
The patient had tested negative for APLS after the first miscarriage in 2019 but tested positive in August 2021 before her fifth pregnancy.
). Regular monitoring of her vaginal microbiota revealed the return of Gardnerella spp. (41.8%) at gestational week six. A second VMT was initially planned for two weeks later, but by the day in question, L. crispatus had once again come to dominate the patient’s microbiota. At the end of the pregnancy, a perfectly healthy baby boy was born via planned cesarean section.
Although they need to be confirmed by further clinical studies, these results suggest that VMT may serve as a treatment for patients with severe vaginal dysbiosis, including those at risk of complications following in vitro fertilization. For the authors, this case study serves as a proof of concept, but it also offers hope for therapies based on the modulation of the vaginal microbiota.
One study suggests that intestinal mucins have a key role in the dysbiosis that sets in as gastric cancer progresses and in its prognosis. The mucins are said to promote the stomach’s colonization by pro-inflammatory oral bacteria.
Prognosis of gastric cancer is difficult as the absence of symptoms in the initial stages of the disease delays its management. Although genetics and environmental factors play a part, the most common cause is Helicobacter pylori infection, which is thought to promote the subsequent arrival of other bacteria (from the mouth or intestines) involved in the tumor’s growth. The (sidenote:
Mucin
Glycoproteins that are the main component of mucus, the complex viscoelastic gel that covers the secretory epithelial cells, protecting them against foreign particles and pathogenic organisms.
Source : Demouveaux B, Gouyer V, Magnien M, et al. La structure des mucines conditionne les propriétés viscoélastiques des gels de mucus [Gel-forming mucins structure governs mucus gels viscoelasticity]. Med Sci (Paris). 2018 Oct;34(10):806-812. French.
) secreted by the digestive mucus seem to also play a role: specific phenotypes of the mucins (gastric in the early stages and intestinal in the advanced stages) are expressed in adenocarcinomas. Is this enough to suggest that there are mucin-microbiota signatures in gastric adenocarcinomas? This is the hypothesis of one Belgian team in any case.
5th
Gastric cancer is the fifth most common cancer type.
4th
Gastric cancer is the fourth leading cause of cancer-related deaths worldwide.
Analysis of the tumor and adjacent non-tumorous tissue in 108 patients who underwent surgery for gastric cancer and biopsies of 20 patients who underwent a gastroscopy due to functional dyspepsia (with no tumor) enabled measurement of the relative expression of gastric mucins (MUC1, MUC5AC and MUC6) and intestinal mucins (MUC2, MUC4 and MUC13). The results show that these three gastric mucins are principally expressed in tumor-free tissue (adjacent or biopsies). Conversely, the overexpression of the intestinal mucin MUC13 proves to be typical of tumors and correlates to a poor prognosis in the development of the cancer.
A mucin-microbiota connection
In terms of bacteria (identified via sequencing of the 16S rRNA gene), several taxa previously associated with gastro-intestinal cancers, in particular Corynebacterium, Fusobacterium, Streptococcus, Porphyromonas and Prevotella, differed significantly between tumorous tissue, adjacent non-cancerous tissue and biopsy tissue. In addition, connections between the bacteria present and the specific phenotype of the mucins in contact with the tumor environment were observed: Helicobacter was more present in tumors without mucins; the taxa (including some that were previously described as oral pathogens) Prevotella, Veillonella and Neisseria seemed to develop more in tumors overexpressing MUC13.
Toward a prognosis for gastric cancer?
Mucins could therefore play a key role in the prognosis of gastric cancer and the formation of the tumor microbiota. An increase in certain oral bacterial taxa associated with an MUC13 overexpression could signal the presence of the disease. Could the mucin-microbiota pair be used as an early marker of the disease? Perhaps, although we should remain cautious for now, as other studies will be required before we can confirm these initial conclusions.
Known as our “second brain”, the gut takes part in a constant two-way dialogue with our real brain. This is known as the gut-brain axis. A breakdown in this axis may be involved in numerous gastrointestinal, metabolic, neurodegenerative, and neuropsychiatric disorders, as well as in certain skin diseases.
Here we tell you everything about the gut-brain axis, how it was discovered, the role played by the microbiota, how communication can be disrupted, and the associated diseases. And we also show you how to influence it.
100 million
The gut nervous system is thought to contain over 100 million neurons
The brain
The brain1,2 is a complex organ. In addition to integrating information from all parts of the body, it also controls thought, memory, emotions, touch, motor skills, vision, breathing, temperature, hunger, and all the mechanisms regulating our body. With the help of a wired network of 100 billion neurons, the brain acts as the body’s control center.
What is the nervous system?
The nervous system3 has two main parts:
The central nervous system which includes the brain and the spinal cord.
The peripheral nervous system which is made up of nerves that run from the spinal cord to all parts of the body.
The nervous system transmits signals between the brain and the rest of the body, including the internal organs.
The enteric nervous system (ENS), a “second brain” inside our gut4,5
The enteric nervous system (ENS) is the nervous system that governs the gut. Comprising a network of neurons that lines the walls of the gastrointestinal tract, it controls the sensory, motor, secretory, and immune activity of the digestive system.
Do you have butterflies in your stomach? Do you often have gut feelings? Or does reading this article get you in the gut?Many popular everyday expressions testify, without our knowing it, to the existence of a link between the gut and the brain.
Did you know?
The gut is sometimes called our second brain. But why?5,6
Because its nervous system is thought to contain over100 million neurons, and it is very similar to the brain in terms of complexity and functionality (neurotransmitters and signal molecules).
The first documented report of a potential link between the gut and the brain dates back to the 19th century.7
The unintentional misadventures of a fur trader advanced science through the discovery of a connection between emotions and gut physiology8,9. Accidentally shot in the stomach at point-blank range, Alexis St. Martin was treated by US Army surgeon Dr. William Beaumont. Surgery had left the patient with an (sidenote:
Fistula
A fistula is an abnormal connection between an organ of the gastrointestinal system and the skin.
) and Dr. Beaumont took the opportunity to observe human digestion in the gut in real time.
During these observations he noticed that the patient’s digestive process was affected by his emotional state, i.e., whether he was angry or irritated. Beaumont thus discovered the existence of a brain-gut axis8. Further scientific studies showed communication between the gut and the brain to be a two-way process from gut to brain and brain to gut, and that the gut microbiota plays a key role in these exchanges8,10,11.
What is the gut-brain axis?
The gut-brain axis can be defined as a bidirectional communication network between the gut and the brain, with the former sending messages to the latter and vice versa. Communication takes place via three different channels8,12:
the neuronal pathway (neurons), mainly via the vagus nerve and the enteric nervous system
the endocrine pathway, through the secretion of hormones such as (sidenote:
Cortisol
Cortisol is known as the stress hormone. It plays a role in responses to physical and/or emotional stress. Cortisol is also involved in maintaining the balance of certain physiological functions, such as blood pressure, the immune system, the metabolism of proteins, carbohydrates, and fat, and anti-inflammatory action.
Katsu Y, Iguchi T, Subchapter 95D - Cortisol.In Ando H, Kazuyoshi U, and Shinji N, eds. Handbook of hormones: comparative endocrinology for basic and clinical research. Pages 533-e95D-2 Academic Press, 2021.
https://www.sciencedirect.com/science/article/abs/pii/B9780128010280002312), (sidenote:
Adrenaline
Adrenaline, also known as epinephrine, is a hormone secreted by the adrenal glands and released into the bloodstream in the event of intense stress, danger, or strong emotions. It prepares the body to fight or flee from danger.
https://my.clevelandclinic.org/health/body/23038-adrenaline), and serotonin
the immune system pathway, through the modulation of cytokines
The gut-brain axis influences our behavior, cognition (memory), emotions, mood, desires, and perception, among other things.
90%
Gut cells are responsible for over 90% of the serotonin production in the body
Did you know?
Serotonin is a neurotransmitter that can affect mood and feelings of happiness and pleasure, as well as appetite. Gut cells are responsible for over 90% of the serotonin production in the body8,13,14. The remaining 10% is produced by “serotonergic” neurons in the brain15. Certain bacteria in the gut microbiota may influence serotonin production in the gut8,16.
Image
Does the microbiota play a role in the dialogue between gut and brain?
The microbiota can be considered the third player in the gut-brain axis, which is also known as the microbiota-gut-brain (MGB) axis.17
The brain, the gut, and the gut microbiota are the three nodes of the microbiota-gut-brain network. These nodes are interconnected and interact bidirectionally. The gut microbiota can communicate with the brain either directly by secreting signal molecules such as (sidenote:
Neurotransmitters
Specific molecules that enable communication between the neurons (the nerve cells in the brain), as well as with the bacteria in the microbiota. They are produced by the individual’s cells and by the bacteria in the microbiota.
Baj A, Moro E, Bistoletti M, Orlandi V, Crema F, Giaroni C. Glutamatergic Signaling Along The Microbiota-Gut-Brain Axis. Int J Mol Sci. 2019;20(6):1482.) or (sidenote:
Short chain fatty acids (SGFA)
Short chain fatty acids are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are implicated in communication between the gut and the brain.
Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25.), or indirectly by interacting with gut cells as an intermediary. Similarly, the brain can modulate the microbiota. It can do so either directly or indirectly by modulating gut physiology in order to alter the microbial environment.
What factors influence communication between the gut and the brain?
Many factors are known to affect the dialogue between the gut and the brain:8
- Diet, and in particular certain foods,such as chocolate, can regulate our mood.The Mediterranean diet is also renowned for its beneficial effects on memory and health. Be careful what you eat. Limit your consumption of processed foods rich in additives, which, according to a recent study on rodents, may cause certain psycho-behavioral disorders (anxiety, reduced sociability, etc.).
- Regular physical activity has many beneficial effects on our health.Physical activity also contributes to good brain health. Numerous scientific studies have shown there to be a link between our cognitive system and our level of physical activity.
- The environment in which we live also has a major impact on our health and microbiota. Pollution is said to increase the risk of respiratory diseases, cancer, and cognitive disorders.
- Some drugs, especially antibiotics, may influence the development of a child’s nervous system and contribute to certain illnesses.
- Scientific studies have shown that the first years of life and the mode of delivery strongly impact our child’s microbiota and thus the gut-brain axis. In fact, several studies have linked cesarean birth to an increased risk of developing a variety of disorders, including obesity and immune system disorders such as asthma or allergies.8 Prenatal stress may also impact a child’s microbiota composition and neurological development, as well as the pregnancy itself, by increasing the risk of premature birth.18
- Stress and fear are also behavioral factors that affect our microbiota and the gut-brain axis.
- Is our behavior also linked to our microbiota? Certain studies suggest so…A healthy microbiota is a prerequisite for good emotional health, drives our libido and sexual desire while in some cases influence our addictive behaviors...
What happens when communication between the gut and the brain is impaired
Disruption of the gut-brain axis is thought to be involved in a range of disorders.
By disruption we mean poor communication between the brain and the gut: either the signals sent are incorrect, or the messages are misunderstood or over-interpreted... In short, the gut and the brain no longer understand each other.Research is advancing our understanding of the gut-brain axis and pointing to the involvement of the gut microbiota in a growing list of diseases.8,17
Below is a non-exhaustive list of pathologies in which a disturbance of the gut-brain axis is thought to be involved.
Let’s take a closer look at some of these disorders:
GASTROINTESTINAL DISORDERS
Irritable bowel syndrome (IBS)
Irritable bowel syndrome (IBS), formerly known as “functional bowel disorder”, is the most common disorder of the gut-brain axis. It is characterized by recurrent abdominal pain, bloating, bowel dysfunction, and other symptoms.
Functional dyspepsia
Functional dyspepsia is a kind of chronic indigestion – a stomachache, a feeling of fullness or bloating during and after meals. It too is a disorder of gut-brain interaction.19,20
Inflammatory bowel disease
Recent studies have shown the involvement of the gut-brain axis in inflammatory bowel disease (IBD)21,22, with the former potentially influencing both disease development and mental health.
METABOLIC DISORDERS
Type 2 diabetes
Type 2 diabetes mellitus (T2DM) is characterized by a chronic excess of sugar in the blood (hyperglycemia) linked to a malfunction in the production or use of insulin, the hormone that regulates blood sugar levels. Cognitive decline is one complication of type 2 diabetes.23
Obesity, excess weight, metabolic syndrome...
These pathologies (obesity, excess weight, metabolic syndrome) are often accompanied by psychological disorders such as anxiety, depression, bipolar disorder, or behavioral alterations.8
The microbiota may also influence what we put on our plate, our feeling of satiety24 as well as our eating habits. Recent studies have shown the role played by the gut microbiota and the gut-brain axis in eating disorders (disturbances in eating or eating-related behavior)25,26
Anorexia nervosa
Anorexia nervosa27,28 is an eating disorder that affects 1% of the population, with women making up 95% of those suffering from the disease. An imbalance of the gut microbiota is thought to contribute to the development and persistence of disorders related to the illness, such as loss of weight and appetite, by acting on the gut-brain axis and the metabolism.
Psychiatric illnesses encompass a wide range of mental disorders, with imbalances in the gut microbiota shown to play a role in several of them.
Anxiety disorders
Anxiety disorders29,30,31 are defined by the WHO as excessive fear and worry as well as related behavioral disorders. Symptoms are severe enough to cause significant distress or major functional impairment. Some anxiety disorders may be linked to the activity of the gut microbiota through the regulation of stress hormones.
Mood disorders
Depression, bipolar disorder, etc. Mood disorders8,32 are emotional disturbances that involve long periods of excessive sadness (depression), excessive cheerfulness or elation (mania), or both of these.
Depression and bipolar disorders have been linked to a gut dysbiosis, with the dysbiosis sometimes correlated with the severity of the symptoms.
Other studies have gone even further by using the gut microbiota as a diagnostic tool.
Obsessive-compulsive disorder (OCD)
Obsessive-compulsive disorder (OCD)33,34,35 is a neuropsychiatric disorder affecting 1.3% of the general population. The disorder is characterized by obsessions (repeated, persistent, unwanted, and often anxiety-provoking ideas or images) which lead to repetitive and time-consuming compulsions and/or avoidance behaviors designed to neutralize the anxiety and anguish resulting from the obsessions. Some studies have suggested that certain butyrate-producing bacteria are less abundant in OCD patients.
Schizophrenia
Schizophrenia8,36,37 affects around 1 in 300 people. This psychiatric illness is characterized by delirium and hallucinations, social isolation, and psychological disruption. Disturbances of the gut microbiota and the immune system are thought to be involved.
Autism spectrum disorders
Autism spectrum disorders (ASD)38 are a heterogeneous group of disorders associated with brain development abnormalities. Symptoms include deficits in communication, social interaction and behavior disorders, as well as repetitive behaviors.
Some studies have shown an altered gut flora (dysbiosis) to be common in autistic patients and certain gut disorders (diarrhea, constipation, etc.) to be frequently associated with the disease.
Gut dysbiosis is thus involved in many psychiatric illnesses such as schizophrenia, depression, and obsessive-compulsive disorder (OCD).
Neurodegenerative diseases are characterized by the gradual destruction of certain neurons.
Alzheimer’s disease
Alzheimer’s disease39,40 is the most common neurodegenerative disorder and the leading cause of dementia.
In recent years, the gut microbiota has been the subject of interest, particularly certain proteins (amyloid peptides) produced by “harmful” bacteria, which may trigger an inflammatory mechanism and disrupt the barrier functions of the gut and the brain, thereby promoting the development of the disease.
Parkinson’s disease
Parkinson’s disease41 is a neurodegenerative disorder that progressively destroys the dopamine neurons in the brain. The disease is characterized by slowness in movements, muscle rigidity, and tremors.
A link to a disruption in the gut microbiota and the gut-brain axis has been shown.
Multiple sclerosis
Multiple sclerosis42,43 is an inflammatory disease of the central nervous system.It is characterized by an “autoimmune response”, whereby the immune system attacks the protective myelin sheath surrounding the neurons.This inflammation leads to a degeneration of nerve cells, or neurons, and a loss of communication between the brain and peripheral organs.
Recent studies have suggested specific associations between the gut microbiota and the risk of multiple sclerosis, its progression and outcome.44
A gut-brain-skin axis?
Did you know?
You may not know it, but the gut and skin have many common features45: both contain numerous blood vessels and nerve connections, both interact with the immune system, and of course both are massively colonized by microbial communities. But that’s not all... have you noticed how your skin reacts to your emotions? Music, fear, excitement... The same applies to certain skin diseases when the gut, the skin, and the brain no longer communicate properly.
As early as 1930, dermatologists John Stokes and Donald Pillsbury46suggested that emotional states such as anxiety or depression could alter the gut microbiota and induce local or systemic inflammation in other organs such as the skin.47 They recommended the use of fermented milk to reintroduce beneficial microorganisms.
Recent years have seen growing evidence for a link between the gut, the brain, and the skin.48 More precisely, stress leads to the secretion of hormones (serotonin, cortisol, etc.), which in turn increase gut permeability, causing local inflammation, while also provoking systemic inflammation via the bloodstream.11,23 Ultimately, this is thought to impact the skin barrier and cause skin inflammation.25 This gut-brain-skin axis is thought to be involved in certain skin diseases: Acne, Atopic dermatitisandPsoriasis
How can we ensure good communication between the gut and the brain?
By now the gut-brain axis is no secret to you. The two-way dialogue exists from gut to brain and brain to gut, with the gut microbiota in between.
But how can we take care of our microbiota so that messages are sent and received loud and clear?
Numerous scientific studies have looked at how to avoid any disruption to microbial composition and how best to preserve its balance49.
What we eat contributes to the balance of our gut microbiota.50,51The food we eat is beneficial when varied and of good quality, but an unbalanced diet can affect the composition of our gut microbiota and lead to certain diseases.52It is therefore important to know which types of food have positive effects on our health53. These include fermented foods or foods naturally rich in prebiotics and beneficial microorganisms, some of which will impact our mental health.These foods may have the ability to boost our morale by acting on the brain via the gut microbiota.54
=> Includes an interview with Professor Rémy Burcelinwho has studied the mechanisms at work between the brain, the gut, and the rest of the body.
What is a psychobiotic?
Psychobiotics are probiotics and prebiotics which, when ingested, provide mental health benefits via the gut microbiota.55
Researchers at University College Cork in Ireland have suggested broadening the definition of psychobiotics beyond probiotics and prebiotics to include any substance that exerts a psychological effect mediated via the gut flora.56
Probiotics are live micro-organisms which, when administered in appropriate quantities, benefit the health of the individual57,58. Some non-clinical and clinical studies have focused on the administration of probiotics to improve symptoms of stress, anxiety, and depression, with results showing promising beneficial effects.8
Prebiotics are specific non-digestible dietary fibers with health benefits.They are selectively used by beneficial microorganisms in the host microbiota.59,60Studies have shown that certain prebiotics have beneficial effects on stress-related disorders.8
To restore the balance of the gut’s microbial ecosystem, patients can be given a fecal microbiota transplant (FMT) from a healthy donor.61 For the moment, this therapeutic approach has only been approved for the treatment of recurrent Clostridioides difficile62 infections, but researchers have expressed considerable interest in it and are assessing its impact on addictions such as alcoholism63 or even on gut-brain interaction disorders such as irritable bowel syndrome.64,65
So suspect scientists. Desulfovibrio bacteria in the gut have recently been accused of inducing aggregates in the digestive system which then spread to the brain via the vagal nerve.
In Parkinson’s disease, alpha-synuclein (alpha-syn) proteins are found to accumulate, in the form of Lewy bodies, in the brain, as well as in numerous other tissues and organs, including the spinal cord, autonomic nerves, myocardial tissue, and the human digestive tract. Some scientists suspect Desulfovibrio bacteria to be involved in the formation of these gut aggregates, which spread in a (sidenote:
Prion
Prions are infectious agents composed of proteins and are associated with specific types of neurodegenerative diseases. For example, bovine spongiform encephalopathy (BSE or “mad cow disease”) is a prion disease that affects cattle and whose human variant is Creutzfeldt-Jakob disease (CJD).
Source: https://www.who.int/fr/news-room/fact-sheets/detail/food-safety)-like manner to the brain via the vagal nerve. Desulfovibrio appears with greater frequency and abundance in Parkinson’s patients, particularly in severe forms of the disease. Are these bacteria, which are known to produce hydrogen sulfide (H2S), really capable of this? A Finnish study on animals attempted to find out, using a C. elegans nematode model expressing human alpha-syn.
10 patients, 10 spouses and nematodes
Three strains of Desulfovibrio (D. desulfuricans, D. fairfieldensis and D. piger) were isolated from the fecal samples of 10 Parkinson’s patients and their 10 healthy spouses at a clinic in Finland. These bacteria were then used to feed the nematodes. In parallel, other worms were fed Escherichia coli MC4100 that produces curli, an amyloid fiber that facilitates alpha-syn aggregation (positive control). A final group of worms were fed a diet containing E. coli LSR11, which is incapable of producing curli (negative control).
8.5 million
Global estimates in 2019 showed over 8.5 million individuals with Parkinson disease.
2x
The prevalence of Parkinson disease has doubled in the past 25 years.
329 000
Parkinson disease caused 329 000 deaths, an increase of over 100% since 2000. Men are more affected than women.
By studying head sections of the worms, it was found that all three strains of Desulfovibrio induced aggregates in the worms’ heads. Those taken from the stools of Parkinson’s patients seemed “more effective” than those taken from the healthy spouses: the worms displayed aggregates that were greater in number and size. Furthermore, worms fed with D. desulfuricans and, to a lesser extent, with D. fairfieldensis harbored significantly larger alpha-syn aggregates than worms fed with D. piger.
An effect on mortality
In terms of survival, after four days, mortality was higher in the group of worms fed with Desulfovibrio from Parkinson’s patients. This increased mortality may be explained by the apparently greater virulence of the bacteria they received, making the bacteria more toxic and inducing more aggregates, at a level that became lethal. The authors believe that the greater virulence of the strains from Parkinson’s patients may relate to the greater or lesser capacity of Desulfovibrio to produce H2S. Indeed, hydrogen sulfide may be involved in alpha-syn aggregation, facilitating the release of cytochrome c from mitochondria.
While this study demonstrates that Desulfovibrio bacteria can increase the number and size of alpha-syn aggregates, many questions remain unanswered, including whether the mechanisms involved include H2S production. Is the presence of these bacteria in stool enough to identify those suffering from the disease? Above all, could eradicating or limiting these pathogenic bacteria help prevent Parkinson’s disease?
Desulfovibrio bacteria in the gut could be responsible for Parkinson’s disease. So concludes a Finnish study that suggests the possibility of screening for, and even preventing, the disease.
What do Pope John Paul II, actor Michael J. Fox (Marty McFly in Back to the Future) and boxer Muhammad Ali have in common? All have been affected by Parkinson’s disease, a degenerative brain disorder characterized by tremors. However, like the nearly 9 million people worldwide affected by the disease, these celebrities also have in common a bacterium called Desulfovibrio. Or to be more precise, an excess of this bacterium, which is thought to be present in (too?) large quantities in Parkinson’s sufferers, particularly those with severe forms of the disease.
Parkinson’s disease: Definition
Parkinson’s disease is a degenerative condition of the brain associated with motor symptoms (slow movement, tremors, rigidity, and imbalance) and other complications, including cognitive impairment, mental health disorders, sleep disorders, and pain and sensory disturbances.A
Gastrointestinal dysfunction is another major feature of Parkinson’s and gut dysbiosis has been observed in patients. Numerous studies have shown that the gut microbiota, via the gut-brain axis, plays an important role in Parkinson’s risk and its progression.B
Are these bacteria responsible for the disease? Yes, according to the results of a Finnish study published in 2023. Their work involved experiments on nematodes – round, slender worms – and, more specifically, worms called C. elegans, which were fed Desulfovibrio bacteria extracted from the stools of Parkinson’s patients or their healthy spouses. The researchers found that the worms fed Desulfovibrio bacteria from the Parkinson’s patients developed protein aggregates in the brain typical of the disease that were greater in number and size when compared to worms fed the same bacteria from the spouses’ stools. In other words, strains of Desulfovibrio bacteria, particularly those from Parkinson’s patients, promote the accumulation of aggregates.
8.5 million
Global estimates in 2019 showed over 8.5 million individuals with Parkinson disease.
329 000 deaths
In 2019, Parkinson disease caused 329 000 deaths, an increase of over 100% since 2000.
Increased mortality
Furthermore, worms fed with Desulfovibrio bacteria from Parkinson’s patients were more likely to die after four days. This excess mortality may be explained by the greater virulence of the bacteria taken from Parkinson’s patients.
This discovery raises enormous hopes of finding a way to identify Parkinson’s patients by tracking the bacteria in their stools, but also of one day being able to slow down or even prevent the disease by eradicating these pathogenic bacteria or simply limiting their number.
The prevalence of Parkinson's disease has doubled in the past 25 years.
People with Cushing's syndrome appear to have a significant imbalance in their gut microbiota for several years after their recovery. This dysbiosis could explain why the risk of diabetes and cardiovascular disease persists in such people.
We know that gut microbiota imbalance has been linked with obesity, insulin resistance, excess triglycerides and cholesterol, all of which are risk factors for diabetes and cardiovascular disease.
If people who have suffered from Cushing's syndrome, a condition caused by a benign tumor of the pituitary gland, have a higher cardiometabolic risk even several years after they have gone into remission, could this also be due to dysbiosis?
To answer this question, a team of Spanish researchers recruited 28 women aged under 60 who had suffered from Cushing's syndrome1. All had been in remission for over five years.
They collected their stool to analyze their microbiota and blood samples to measure various cardiovascular risk parameters. They also examined their body fat distribution.
As expected, the women in remission had several more cardiovascular risk factors than the healthy volunteers, namely more abdominal fat, higher levels of glycated hemoglobin, triglycerides and fasting glucose, less 'good' cholesterol (HDL), etc.
In addition, all had acute intestinal dysbiosis. Not only were their microbiota less rich and diverse, but they also had a very different structure.
For example, the Suturella strain, which was absent in the control group, was present in abundance in the women in the Cushing's syndrome group. A number of studies have reported the presence of this bacterium in people suffering from diabetes, obesity, excess insulin, atherosclerosis, etc.
Excess cortisol wreaks havoc in Cushing's syndrome
Cushing's syndrome is a relatively rare condition caused by a benign tumor of the pituitary gland, a small gland in the brain that controls many of the body's functions2. This anomaly affects women more than men. It leads to over-stimulation of the adrenal glands which secrete cortisol.
Exposure of the organs to this excess cortisol causes a number of symptoms, some of which increase the risk of cardiovascular disease, and include:
Accumulation of fat around the torso, viscera and face,
Excess glucose, triglycerides, and cholesterol,
Insulin resistance,
Increased blood pressure,
Muscle atrophy and osteoporosis,
Increased hair growth,
Infertility, sexual disorders, etc.
Treatment includes surgery (removal of the tumor), medication and radiotherapy.
The persistence of metabolic disorders in former Cushing's patients may be linked to dysbiosis
Surprisingly, in former patients, the index measuring bacterial diversity was associated with fibrinogen levels, a protein involved in coagulation, and therefore linked to the risk of vascular accident. In addition, this index was inversely correlated with triglycerides, blood glucose and insulin levels.
This suggests that the persistence of metabolic disorders in former Cushing's patients is very probably linked to dysbiosis.
This is the first time that such a link has been scientifically demonstrated.
These results need to be confirmed by larger-scale studies. They do, however, point to the possibility that one day we may be able to intervene in a targeted manner, either through probiotics or fecal microbiota transplant (FMT), to restore the microbiota balance in people suffering from Cushing's syndrome.
As a result, years of healthy life could be gained!
A study published in Science of the Total Environment1 revealed clouds carry large quantities of various bacterial antibiotic resistance genes. Generated by antibiotics released into the environment, these genes can travel long distances.
Each year, tens of thousands of tons of antibiotics are used for healthcare purposes in humans, animals, and plants, a portion of which is released into the environment. Antibiotics are thus found not only in wastewater, but also in rivers, the sea, and soil, enabling environmental bacteria to acquire resistance genes that can then be transferred to other bacteria. Bacterial cells and genetic material can aerosolize and, due to air turbulence, rise into the atmosphere, travel long distances, and then become part of the water cycle.
Antibiotic resistance has been classified as one of the 10 biggest threats for human societies in the near future.
Proof of a “resistome” in the clouds
A French and Canadian research team assessed the quantity of antibiotic resistance genes in clouds at the Puy de Dôme meteorological observatory in France’s Massif Central, at an altitude of 1,465 meters. Twelve samples were taken with a high-flow vacuum between September 2019 and October 2021, revealing an average concentration of around 5,400 copies of resistance genes per cubic meter of air (measured by flow cytometry). The 33 resistance genes found correspond to the main antibiotic families in use today: quinolones, sulfonamides, tetracyclines, aminoglycosides, glycopeptides, β-lactam antibiotics, and macrolides. Of these, 29 were detected at least once, and 6 were observed in at least 75% of samples.
Rather than varying with the seasons, the distribution of these genes varied according to the geographical origin of the air masses. Resistance genes for the quinolone family, antibiotics strongly implicated in antibiotic resistance and whose use has been restricted in Europe since 2018, were more abundant in high marine clouds. Resistance genes for the sulfonamide and tetracycline families were more abundant in clouds formed over continental surfaces, perhaps due to their widespread use in livestock farming.
4.95 million
In 2019, >4.95 million deaths were associated with antimicrobial resistance
1.27 million
In 2019, 1.27 million were directly attributed to antibiotic-resistant bacterial infections
The atmosphere is a major highway for resistome dissemination
Considering the average concentration of resistance genes in clouds according to the study (5,400/m3 of air), the researchers estimate that clouds permanently carry around 2.53 × 1021 copies of resistance genes worldwide. Thus, each year, between 1.29 × 1025 and 2.06 × 1026 resistance genes may be transported by clouds, with a very large quantity of these genes (2.2 ×1024) falling to earth through precipitation (and a fraction remaining evaporated in the atmosphere).
This study has found the atmosphere to be one of the routes by which antibiotic resistance factors are disseminated worldwide. Studies that pinpoint the sources of bacterial emissions may limit their dispersal.2
Each year, since 2015, the WHO organizes the World AMR Awareness Week (WAAW), which aims to increase awareness of global antimicrobial resistance.
Held on 18-24 November, this campaign encourages the general public, healthcare professionals and decision-makers to use antimicrobials carefully, to prevent the further emergence of antimicrobial resistance.
Antibiotic resistance is a major public health concern that reaches the whole world... including by air. Large quantities of genes from antibiotic-resistant bacteria have been found in clouds. As they spread into the atmosphere, they can travel long distances.
The fact that bacteria adapt to resist antibiotics is a natural evolutionary phenomenon. But the massive use of these drugs to treat human, animal and plant infections has greatly amplified it. And every year, a good proportion of the tons of antibiotics used end up in the environment, namely in soil, rivers, oceans, etc. Resistant bacteria can develop there, transmit their resistance genes to other bacteria and disperse with the wind and reach high altitudes. Although the atmosphere is not a suitable environment for their survival, fragments and genetic material can still reach the clouds, travel from one continent to another and return to dry land through rain.
Bacterial resistance to antibiotics is a public health issue
Antibiotic resistance has been ranked as one of the top 10 threats to human health in the near future. In 2019, nearly five million deaths were linked to antimicrobial resistance and almost 1.3 million were directly attributed to antibiotic-resistant infections. If nothing is done, 10 million people could die by 2050, making antibiotic resistance the world's leading cause of death.
Clouds vacuumed up into test tubes
At the Puy-de-Dôme weather station located at an altitude of 1,465 meters in the French Massif Central, Franco-Canadian researchers spent two years taking 12 "cloud samples" with a special vacuum cleaner aimed at nimbus and cumulus clouds. For each sample, they measured the quantity of bacteria and 33 resistance genes corresponding to the main antibiotics used today. Of these, 29 were detected at least once and 6 were observed in at least 75% of the samples. The clouds contained an average of 8,000 bacteria mainly of plant origin, of which 5 to 50% could be alive and potentially active, and over 20,000 copies of antibiotic resistance genes per milliliter of water.1,2
The researchers found that the distribution of these genes varied according to the geographical origin of the air masses sampled. For example, genes for resistance to quinolones (antibiotics whose use has been restricted for several years due to the antibiotic resistance they promote) were more abundant in high ocean clouds. Sulfonamide and tetracycline resistance genes were more prevalent in clouds formed over continental surfaces, perhaps due to their widespread use in livestock farming.
Reservoirs of antibiotic resistance genes hovering over our heads
The researchers extrapolated their measurements to the total volume of clouds around the earth, assuming that all would have the same concentration of antibiotic resistance genes. The results showed that every year, around 70 trillions of trillions (1024) of these genes pass through the clouds, of which around 3% could potentially fall back down to the earth's surface.
This study highlights the role of the atmosphere as one of the routes by which antibiotic resistance factors are disseminated worldwide. Additional studies to pinpoint the sources of bacterial emissions could help limit their dispersion.
What is the World AMR Awareness Week?
Each year, since 2015, the WHO organizes the World AMR Awareness Week (WAAW), which aims to increase awareness of global antimicrobial resistance.
Antimicrobial resistance occurs when bacteria, viruses, parasites and fungi change over time and no longer respond to medicines. As a result of drug resistance, antibiotics and other antimicrobial medicines become ineffective and infections become increasingly difficult or impossible to treat, increasing the risk of disease spread, severe illness and death.
Held on 18-24 November, this campaign encourages the general public, healthcare professionals and decision-makers to use antibiotics, antivirals, antifungals and antiparasitics carefully, to prevent the further emergence of antimicrobial resistance.
A Canadian clinical study recommends taking advantage of the remission phases of ulcerative colitis to follow a Mediterranean diet in order to reduce the frequency of flare-ups and underlines the importance of adopting a healthier diet in addition to treatment.
The symptoms of ulcerative colitis, i.e., bloody diarrhea, abdominal pain, cramps, tenesmus and fatigue, have a major impact on the quality of life of patients. Altered gut microbiota may lie at the root of the problem. However, this same microbiota is influenced by diet. That is why this randomized controlled trial was set up by researchers and clinicians at the University of British Columbia, Canada. They assessed the effectiveness of the Mediterranean diet in treating symptoms, inflammation and gut microbiota. The adults recruited (65% women, median age 47) either adopted a Mediterranean diet for 12 weeks, with advice from a dietitian (15 patients), or continued with their usual diet (13 patients, control group).
Preventing ulcerative colitis relapses
At the end of the 12-week study, the Mediterranean diet was well tolerated and reduced the frequency of attacks. Although all patients (except one experiencing a benign episode) were in remission at the start, slight activity was observed in one-third of the patients in the Mediterranean group while almost half of the patients in the control group suffered from a mild-moderate attack. The Mediterranean diet also helped to reduce fecal calprotectin levels which predict impending relapses and measure intestinal inflammation: 20% of patients on this diet had levels above 100 μg/g compared with 75% of those in the control group.
Prevalence of ulcerative colitis
The prevalence of ulcerative colitis ranges from 114 cases/100,000 inhabitants in Asia and the Middle East to 505 cases/100,000 inhabitants in Europe.
Microbiota analysis also showed the benefits of the Mediterranean diet, with an increased presence of protective bacteria, notably Firmicutes (Ruminococcus spp., Flavonifractor spp., Clostridium M, Blautia A, and Lactococcus spp.), as well as a decrease in potentially pathogenic bacteria such as Veillonelladispar, Veillonella obetsuensis, Prevotella copri, Streptococcus australis, and biofilm-forming species. The researchers also observed a significant increase in fecal secretory immunoglobulin A (sIgA) after 12 weeks on the Mediterranean diet. This sIgA plays an essential role in maintaining mucosal homeostasis as it binds to pathogenic bacteria and prevents them from gaining access to the intestinal epithelium. Fecal secretory immunoglobulin A could thus explain the negative association between opportunistic pathobionts and the Mediterranean diet.
More short-chain fatty acids
Lastly, the Mediterranean diet coincided with an increase in the production of short-chain fatty acids (SCFAs), known for their immunomodulatory properties and role in promoting intestinal homeostasis, with observed higher levels of total SCFAs as well as butyric, acetic and valeric acids.
As such, the well-tolerated Mediterranean diet appears to be a reasonable and healthy dietary model that can be an option for ulcerative colitis patients in remission to prevent relapses, in addition to their standard medical treatment.
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