According to a major metagenomic study published in Nature Communications1, Parkinson’s disease is accompanied by a widespread gut dysbiosis that may be involved in several of the disease’s pathogenic mechanisms.
Parkinson’s disease is a significant cause of disability and death. The prevalence of the disease has doubled in the past 25 years, with an estimated 8.5 million people affected as of 20192. The disease’s etiology remains poorly understood, but it may be caused by a combination of genetic susceptibility and environmental factors. Parkinson’s disease is a neurodegenerative disorder that is now considered both a movement disorder and a multi-systemic disease. The connection between the disease and the digestive system has long been established, with symptoms including constipation (generally the earliest sign), a compromised gut barrier, and inflammation.
8.5 million
Parkinson's disease affected 8.5 million people worldwide in 2019.
The hypothesis that an enteric bacterial neurotoxin triggers the disease (Braak’s hypothesis) is gaining increasing scientific support. However, all studies focusing on the gut microbiota have given mixed results due to the use of cohorts of limited size and low-resolution sequencing technology.
Largest study of gut microbiome to date
A research team in the US put together a cohort of unprecedented size, including 490 Parkinson’s patients and 234 neurologically healthy controls. About 50 variables were analyzed, such as the presence of digestive disorders, medication intake, and diet. The participants’ gut microbiome was analyzed via deep shotgun sequencing.
Unsurprisingly, constipation was much more common in the Parkinson’s group. At the microbiome level, up to 30% of the species, bacterial genes, and signaling pathways were altered in the Parkinson’s patients. 55 species were more abundant in the Parkinson’s patients, including Bifidobacterium dentium, Actinomyces oris, Streptococcus mutans, and Lactobacillus fermentum, while 29 others were depleted, including Roseburia, Eubacterium, Ruminococcus, and Faecalibacterium prausnitzii, species known to produce (sidenote:
Short chain fatty acids (SCFA)
Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine 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.)
Major dysbiosis promotes known mechanisms for the disease
Several mechanisms characteristic of Parkinson’s disease were thus identified. Among the 55 species enriched in the gut microbiota of Parkinson’s patients, 11 are opportunistic pathogens (Porphyromonas asaccharolytica, Escherichia coli, Klebsiella) that have lipopolysaccharides on their surface. Lipopolysaccharides cause an immune reaction by releasing pro-inflammatory cytokines into the body.
On the other hand, there was a reduction in species, genes, and pathways that degrade polysaccharides and produce SCFAs. In the gut, inadequate levels of SCFAs were linked to constipation, a weakening of the gut barrier, and inflammation, all characteristic symptoms of the disease.
They also found a dysregulation in the synthesis and metabolism of neuroactive molecules dopamine, glutamate, GABA, and serotonin; preponderance of molecules that induce alpha-synuclein pathology and over-production of toxicants; and a reduction in anti-inflammatory and neuroprotective factors, such as nicotinamide or trehalose.
The researchers thus confirm observations previously made in animals. They intend to further their investigations by continuing to study the gut microbiome: it may be possible to define subtypes of the disease and identify biomarkers for disease progression, while manipulating it may allow us to prevent, treat, and slow progression of the disease.
Herbs and spices seem to be able to modulate the gut microbiota of adults at risk of cardiovascular disease and to boost a family of beneficial bacteria, the Ruminococcaceae.
Our diet remains the easiest way to modulate the gut microbiota, since the bacteria that colonize the gut feed on undigested food compounds, such as fibers and polyphenols. Such compounds are found in abundance in vegetables. Other polyphenol-rich foods that benefit our gut microbiota are herbs and spices. How exactly do they effect the bacterial composition of the gut?
A (sidenote:
Randomized trial
Study in which the products tested are distributed randomly, between the participants.
), (sidenote:
Controlled trial
a study in which participants are given either a test product (capsule containing the active compound) or a placebo (control capsule not containing the active compound), thus allowing for comparison.
), (sidenote:
Double-blind trial
both the participants and the researchers are unaware who has received the test product (capsule containing the active compound) and who has received a placebo (control capsule not containing the active compound).
) conducted on 54 American adults at risk of cardiovascular disease provided the answers. During three successive four-week periods (separated by washout periods of at least two weeks), the participants were fed a classic American diet enriched with a mixture of herbs and spices in various concentrations.
Risk of cardiovascular disease :
Overweight,
Extra waist circumference,
At least one other risk factor (high blood sugar, low HDL cholesterol, elevated triglycerides, hypertension...).
American diet enriched with a mixture of herbs and spices:
Cinnamon (20%),
Oregano (30%),
Ginger (30%),
Black pepper (17%),
Cayenne pepper (3%).
Boosting Ruminococcaceae
The result: this simple mixture modified the participants’ gut flora. Bacterial diversity increased with the dose (higher diversity with 3.3 g/d than with 0.5 g/d) and compared to the initial diversity. However, the latter result should be viewed with caution, since it may be due as much to the change in diet among the participants (who were provided with standardized meals) as to the herb and spice capsules.
The second finding of the study is that meals rich in herbs and spices seem to go hand in hand with a higher presence of beneficial bacteria, primarily from the Ruminococcaceae family. According to a previous study, these bacteria are associated with lower long-term weight gain. The consumption of spices also enriched the Agathobacter genus and the bacterium Faecalibacterium, which produce (sidenote:
Short chain fatty acids (SCFA)
Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine 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.), such as butyrate and propionic acid, whose benefits include their anti-inflammatory effects.
Do spices naturally boost a gut microbiota beneficial to our health? This avenue needs to be explored further. In the meantime, add some herbs and spices to your menu...
Affecting 5 to 10% of the global population, irritable bowel syndrome (IBS) is one of the most common functional bowel disorders (FBD) now called “disorder of Gut Brain interaction” (DGBI). What do we know about it? Why is the finger often pointed at microbiota? How to live with the illness? To mark IBS awareness month, Biocodex Microbiota Institute offers you a mix of articles, testimonies and opinions to raise awareness about this pathology.
The Biocodex Microbiota Institute’s goal is to educate the general public and healthcare professionals about the human microbiota. It does not provide medical advice. Please consult a health professional for any questions or requests you may have.
According to a Chinese longitudinal study, a higher relative abundance of L. iners bacteria in the vagina reduces the chances of human papillomavirus (HPV) being cleared spontaneously twelve months after infection. This potential therapeutic target merits further exploration as part of the fight against cervical cancer.
Sexual infection by a human papillomavirus (HPV) is common and is usually transitory, disappearing within 24 months in 80% of cases. However, for one in five women infection persists. High-risk human papillomavirus (HR-HPV) is the leading cause of cervical cancer. Sexual activity, smoking, and oral contraception are among the many factors that influence initial infection, the resolution or the onset of HR-HPV, and potential progression to cancer. In recent years, the vaginal microbiota has been added to this list. The value of this study is therefore clear, since it monitored the cervical microbiota of HR-HPV infected Chinese women presenting histologically confirmed, and mostly low-grade, cervical lesions.
More L. iners, less spontaneous clearance
A 16S rRNA analysis of the microbiota of the 73 participants in the study (aged between 24 and 68 years) showed that HPV had disappeared in 45 of the women (61.6%) by the end of the twelve-month study period. The clearance or otherwise of the virus was not due to differences in the patients’ age, the stage of the disease, the HPV subtype, the (sidenote:
Community state types
Five types of vaginal community have been identified, four dominated by lactobacilli (Lactobacillus crispatus, L. gasseri, L. iners, and L. jensenii) and a fifth characterized by a low lactobacilli content.
), or vaginal microbiota diversity. Instead, certain bacterial species seem to be involved: women depleted in enterococcus ASV_62 and enriched in Lactobacillus iners at baseline were less likely to have HPV-HR clearance at month twelve. The only exception was 22 women who underwent surgical treatment (conization) for high-grade lesions, perhaps because the immediate impact of lesion resection on HPV clearance masked the impact of the flora.
99 %
of all cervical cancer cases are linked to infection with papillomavirus, an extremely common virus transmitted through sexual contact.
4th
Cervical cancer is the fourth most common cancer in women.
570,000 women
In 2018, an estimated 570,000 women were diagnosed with cervical cancer worldwide and about 311,000 women died from the disease.
A possible link between L. iners and HR-HPV had previously been reported by a meta-analysis suggesting a two- or even three-fold higher risk of persistent HR-HPV when the vaginal microbiota is dominated by L. iners. This bacterium appears to be both flexible and adaptable, dominating the vaginal microbiota of certain women during menstruation or episodes of bacterial vaginosis. On the other hand, a vaginal microbiota dominated by L. iners (CST III) is frequently reported as one of the most common types of vaginal bacterial community among Asian child-bearing age women. Therefore, it is not yet clear from the current literature whether this particular strain of Lactobacillus should be considered beneficial, pathogenic, or both. Further work is also needed to clarify the mechanisms by which L. iners promotes persistent HPV infection or lesion progression, especially since the current study involved a small number of patients, certain confounding factors, such as smoking, were not taken into account, and it lasted only one year, whereas a 24-month follow-up is required.
Papillomavirus (HPV) is a common infection that leads to cervical cancer in some women, but not in others, for whom the virus is cleared after a few months. This resistance may be due to certain bacteria in the vaginal microbiota.
Cervical cancer is the fourth most common cancer in women. 99% of all cases follow infection with papillomavirus (HPV), an extremely common virus transmitted through sexual contact. Fortunately, in 80% of cases, HPV disappears spontaneously within two years of infection. However, for one in five women infection persists and may lead to cervical cancer. Why are some women unable to eliminate it? And why do some develop pre-cancerous lesions as a result of the virus? Chinese researchers have attempted to answer all these questions.
They believe the vaginal microbiota is involved. Previous studies had observed a vaginal dysbiosis in infected patients: high abundance of certain lactobacilli appears to reduce the risk of infection, whereas the lactobacillus L. iners is more frequent in infected patients. However, the studies’ findings are at times contradictory. As a result, researchers in Shanghai carried out this complementary study on 73 women infected by HPV and presenting first lesions of the cervix.
27%
Only 27% of women surveyed say they know that the vaginal microbiota is balanced when its bacterial diversity is low
Almost two out of three patients saw HPV clearance after one year, with the rest remaining infected. The persistence or otherwise of the virus was not due to differences in the patients’ age, the stage of the disease, the HPV subtype, the type of vaginal bacterial community (there are five main types, somewhat like blood groups), or vaginal microbiota diversity. On the other hand, the presence of two specific bacteria seemed to be involved: women with depleted levels of enterococcus ASV_62 in their cervix and enriched in L. iners were less likely to have cleared HPV after one year.
99%
of all cervical cancer cases are linked to infection with human papillomavirus (HPV), an extremely common virus transmitted through sexual contact.
4th
Cervical cancer is the fourth most common cancer in women.
604,000
In 2020, an estimated 604,000 women were diagnosed with cervical cancer worldwide and about 342,000 women died from the disease.
Will future treatments target these two bacteria (promoting one and reducing the other) to drive out HPV and prevent cervical cancer? Perhaps...if further studies support these findings. In the meantime, HPV vaccination for teenagers and regular cervical cancer screening (vaginal smears to detect precancerous lesions) for all women aged 25 to 65 is enough to prevent most cases of cervical cancer.
A study published in Molecular Psychiatry reveals that a diet emphasizing foods with an effect on brain processes via gut microbiota may reduce perceived stress in just 4 weeks. Based on their results, the authors believe that nutritional approaches aimed at modulating gut microbiota may improve mental health.
Numerous scientific studies have highlighted the involvement of gut microbiota in brain processes, mental health, behavior and cognitive function. They have opened a door for psychobiotics, i.e. interventions that impact the brain by modulating gut microbiota. Prebiotics and probiotics have already shown promising results in animal and human studies. Moreover, it is known that diet plays a major role in the composition of gut microbiota and is thought be involved in certain mental disorders.
A menu rich in prebiotics is beneficial to gut microbiota
Most studies of gut microbiota-host interactions focus on the effect of supplementation with certain foods. An Irish team decided to measure the effect of a psychobiotic diet through a single-blind, randomized, controlled clinical study. Over 4 weeks, the impact of this diet on gut microbiota, mood and perceived stress was evaluated. The researchers enrolled 24 participants and 21 healthy adult controls (18-59 years of age). The first group was offered a diet that included whole grains (5 to 8 servings), fruits and vegetables high in prebiotics (6 to 8 servings of onions, lettuce, cabbage, apple, etc.), other vegetables (3 to 4 servings) and fermented foods (2 to 3 servings of sauerkraut, kefir or kombucha) each day. They were asked to reduce sweets, sodas and fast food. Participants also received general dietary advice: food pyramid, daily calorie recommendations according to sex, etc. The control subjects received only this dietary advice. Stress experienced by all subjects was self-assessed using Cohen’s Perceived Stress Scale (PSS) at inclusion and at the end of the study.
A decrease in stress and changes in bacterial metabolic activity
At the end of the 4 weeks, both groups had benefited from the change in eating habits, with a decrease in perceived stress levels. However, this reduction was significant only in the psychobiotic diet group. In addition, the reduction in PSS score was correlated with the degree of adherence to the psychobiotic diet. Slight differences in the composition of the gut microbiota of the psychobiotic group compared to inclusion were observed (increase in Blautia wexlerae and B. obeum, decrease in Coprococcus comes, Dorea longicatena, Eubacterium rectale, Gemmiger formicilis and Bifidobacterium longum). However, metabolomic analysis revealed a significant change in 40 lipid metabolites in the psychobiotic diet group and not in the control group. This change could result from the reduced dietary fat intake associated with the psychobiotic diet, but may also suggest that gut microbiota influences mood by regulating lipid metabolism.
Results that will feed future nutritional recommendations?
According to the authors, the development of psychobiotic approaches that modulate the gut-brain axis offers possibilities for reducing stress and associated disorders. Larger studies must not only confirm the effect of such a diet on stress, but also clarify the underlying mechanisms and the role of gut microbiota in these benefits. Their results could give dietary interventions a bigger role in future nutritional recommendations for the prevention or treatment of mental disorders.
Ways of reducing anxiety and managing stress on a daily basis would be embraced by a large part of the population left exhausted by the daily grind! A study has revealed that opting for a diet rich in compounds beneficial to gut microbiota, or “psychobiotics,” may be one way to achieve this.
From having a knot or butterflies in our stomach to not being able to digest bad news... we all know how emotions can have a “visceral” effect on the constant discussion between our gut and our brain. This “gut-brain axis,” which passes through our digestive microbiota, has opened up huge avenues in terms of new knowledge... and solutions to improve our physical and mental well-being. Many scientific studies are thus revealing the role of gut microbiota in our brain mechanisms, and therefore our (sidenote:
Cognition
All the mental processes related to knowledge that involve attention, learning, intelligence, language, memory, perception, decision-making, problem-solving, reasoning, etc.
Cognition_National Cancer Institute) and mental health.
Anxiety, depression and certain mood disorders are thereby thought to be associated with intestinal dysbiosis. Given that diet plays an important role in our gut microbiota balance, it may therefore be used as a way to lift our morale, especially if it contains psychobiotic compounds (which act on the brain via gut microbiota), for example fermented foods or foods naturally rich in prebiotics.
What is a psychobiotic diet?
Particularly beneficial for gut microbiota, a psychobiotic diet emphasizes consumption of prebiotic foods (onions, lettuce, cabbage, apples, bananas, whole grains, etc.) and fermented foods (sauerkraut, kefir, kombucha, etc.).
The effect of psychobiotics through diet
Consequently, a team of researchers explored the impact of a 4-week psychobiotic diet on gut microbiota as well as on the mood and stress levels of 24 healthy adults, compared with 21 control subjects. The diet of the “psychobiotic” group was rich in foods beneficial to gut microbiota, with whole grains, fruits and vegetables high in prebiotics (onions, lettuce, cabbage, apples, bananas, etc.) and fermented foods (sauerkraut, kefir, kombucha), while sweets, sodas and fast food were reduced to a minimum. The control group was guided simply by classic nutritional advice, encouraging a balanced diet.
Image
Less stress in less than a month
At the end of the 4 weeks, both groups had benefited from the change in eating habits, with a decrease in the participants’ perceived stress levels compared to the beginning of the study. However, this reduction was significant (32%) only in the “psychobiotic” group, and the more diligently they followed their diet, the greater the reduction. Analysis of participants’ stool samples revealed only slight differences in the composition of their gut microbiota. However, a significant change in certain compounds, called lipid (sidenote:
Metabolites
Small molecules produced during cellular or bacterial metabolism. For example, short-chain fatty acids are metabolites produced by intestinal microbiota during fermentation of non-digestible complex carbohydrates (fibers, etc.).
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.Lamichhane S, Sen P, Dickens AM, et al An overview of metabolomics data analysis: current tools and future perspectives. Comprehensive analytical chemistry. 2018 ; 82: 387-413), was observed in the psychobiotic group (but not in the control group). According to the researchers, this may be explained by the reduced dietary fat intake associated with the psychobiotic diet, but may also suggest that gut microbiota influences mood by regulating fat metabolism.
Feeding our gut microbiota properly could therefore help us reduce our stress. Longer studies involving a larger number of individuals are now needed to confirm the effect of a psychobiotic diet on stress, and to clarify the underlying mechanisms and the role of gut microbiota in these benefits.
In schizophrenic adults, a pro-inflammatory phenotype, oxidative stress, dysbiosis and intestinal permeability are associated with aggressive behavior. This could lead to future microbial or anti-inflammatory therapies.
Schizophrenia affects 1% of the adult population, especially young adults. This psychiatric disease is thought to increase the propensity for aggressiveness, although we do not really know why. Nevertheless, some leads are emerging, involving the intestinal microbiota and a possible bacterial translocation in case of loss of watertightness of the intestinal mucosa. Following this hypothesis, a recent study profiled the diversity and composition of the intestinal microbiota, certain fecal (sidenote:
Short chain fatty acids (SCFA)
Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine 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.) (short chain fatty acids) and neurotransmitters of 50 schizophrenic patients, 25 of whom had aggressive behaviors. Objective: to understand the link between inflammation, oxidation, intestinal permeability and microbiota in schizophrenic patients with aggressive behavior.
An inflammatory phenotype...
The results show that schizophrenic patients with aggressive tendencies had significantly increased levels of serum biomarkers of nucleic acid and lipid oxidation compared to non-aggressive schizophrenic patients. These pro-oxidative and pro-inflammatory responses were related to the severity of aggression, suggesting a co-implication of systemic inflammation and oxidation in the development of aggression in schizophrenia.
1%
of the global populations are affected by schizophrenia.
4 to 7
Schizophrenia may augment the propensity for aggression incidence about fourfold to sevenfold.
... coupled with bacterial dysbiosis
Schizophrenic patients with aggressive tendencies also showed a much lower bacterial diversity. This intestinal dysbiosis thus seems to be correlated with the etiology or the severity of aggressiveness in schizophrenic individuals, although it cannot be concluded that there is a causal relationship.
Furthermore, the abundance of the genus Prevotella was significantly increased, while Bacteroides, Faecalibacterium, Blautia, Bifidobacterium, Collinsella and Eubacterium coprostanoligenes were greatly depleted in the group of patients with aggressive tendencies. This change was accompanied by significant reductions in some metabolites, although the authors could not establish a causal relationship: 6 fecal SCFAs (acetic, propanoic, butyric, isobutyric, isovaleric, and isohexanoic acids) and 6 neurotransmitters (5-hydroxytryptophan, levodopa, norepinephrine hydrochloride, adrenaline hydrochloride, kynurenic acid, and histidine) were found to be significantly less present in patients with aggressive behavior.
A hypothesis to be confirmed
Considering these results as a whole, the authors hypothesize that the systemic pro-inflammatory phenotype previously observed in schizophrenics with aggressive tendencies would involve alterations of the intestinal microbiota and its metabolites, hyper-permeability of the intestinal wall allowing intestinal bacteria to reach the general circulation by causing oxidative stress, linked to the severity of the aggressive character. Thus, hyper-inflammation would have led, via the intestinal microbiota, to hyper-oxidation and ultimately to aggressiveness. This hypothesis has yet to be validated in larger-scale studies.
What do sauerkraut, kombucha, sourdough bread and kefir all have in common1? They are fermented foods, and scientists are taking increasing interest in their health benefits. An American study2 has revealed that eating a portion of fermented vegetables daily is beneficial for gut microbiota after just 6 weeks.
According to the official scientific definition, fermented foods are “foods made through desired microbial growth and enzymatic conversions of food components”3. More simply, they are processed using microorganisms such as lactobacilli (“lacto-fermented” foods) and other species of bacteria, filamentous fungi or yeast3. These foods provide beneficial microorganisms, vitamins, prebiotics and bioactive compounds of plant origin that balance gut microbiota. According to various studies3,4, they are also thought to have digestive and metabolic benefits.
5,000 fermented foods
Over 5,000 fermented foods and beverages are listed worldwide, representing between 5 and 40% of the human diet.
So why not include fermented foods in our daily diet to improve our health? A team of researchers decided to evaluate the feasibility and effects of consuming fermented vegetables (cabbage and pickles) for 6 weeks on the composition of the gut microbiota of 31 women. The participants were divided into three groups: the first consumed 100 g of fermented vegetables per day, the second 100 g of the same vegetables in brine (not fermented but preserved by acidification3) per day, and the third group, a control group, were asked to continue eating as usual. Stool samples were collected at the beginning and end of the study to analyze the gut microbiota.
Results: The gut microbiota of the women who consumed fermented vegetables was richer in Faecalibacterium prausnitzii, which according to studies are abundant in healthy people and protect against inflammation, oxidative stress and pathogenic germs. There were also fewer Ruminococcustorques bacteria, thought to promote inflammation and metabolic problems. Overall, their microbiota had more diverse microbial communities, beneficial for its balance.
In terms of digestion, the women consuming fermented vegetables experienced more bloating than those not consuming vegetables, which was expected because of the cabbage, a well-known source of natural gas! However, they also experienced less diarrhea than those consuming brined vegetables, suggesting that fermenting vegetables improves stool consistency, and less stomach upset than the other two groups. Finally, in terms of regularity, while 70 to 90% of the women in the “cabbage-pickles” groups stuck to their diet, some found it tough on reaching the end of the 6 weeks...
This pilot study suggests that consuming 100 g of fermented vegetables daily for 6 weeks is feasible and beneficial for gut microbiota: more work is now necessary to determine whether fermented vegetables could effectively fight dysbiosis. Its authors suggest offering participants a wider variety of vegetables to reduce the side effects and boredom.
March is Endometriosis Awareness Month. Painful, complex and often undiagnosed, endometriosis is a chronic gynecological disease affecting one in every 10 women of reproductive age1.
Actively supporting this worldwide campaign since 2021, Biocodex Microbiota Institute keeps on exploring the link between the microbiota and endometriosis. Can the vaginal microbiota be used as a tool for predicting the severity of the disease? What about the gut microbiota? Is the vaginal microbiota to blame for painful periods? All your questions answered here.
On this occasion, the Institute sheds the lights on a little-known topic: periods and endometriosis. Do gut and vaginal microbiota play a role in it?
SCFAs: new intestinal markers of Parkinson’s disease?
Role of the microbiota in gut-brain communication
