Atherosclerosis

Atherosclerosis is characterized by an accumulation of fat on the walls of arteries, which can range from a simple narrowing to the complete obstruction of the blood vessel. New ideas for prevention are targeting diet and intestinal flora.

The gut microbiota

Atheromatous plaques, or lipid plaques consisting of cholesterol in particular, are very common; all adults have them. Their thickening can obstruct blood flow, meaning organs are no longer sufficiently supplied, which can lead to pain and changes in heart rate. A local inflammatory reaction can lead to plaque rupture. When plaques become unstable and break off, the results are dramatic: this is the cause of 80% of cases of sudden death. Plaque rupture can also cause myocardial infarction or stroke. Although there seems to be a genetic predisposition, risk factors have been identified: an excess of cholesterol and smoking.

Bacteria and diet in question

Intestinal microbiota may contribute to plaque vulnerability, and therefore to rupture. Some bacteria, as well as the components that they produce, could cause an inflammatory reaction that could eventually lead to atheromatous plaque rupture. Dysbiosis, an imbalance in the composition of the microbiota, might also increase the risk of atherosclerosis in cases of high lipid diets. Bacteria appear to play an important role, because it has even been shown that infections are risk factors for atherosclerosis--gum infections (periodontitis) in particular.

From prevention to probiotics

Prevention is crucial: diet, weight loss, stopping smoking, etc. However, some medications can have a beneficial effect in high-risk people with atherosclerosis. Studies are being conducted to find out if diet or probiotics could reduce the risk of atherosclerosis. The Mediterranean diet is also very beneficial. A new era of therapy could directly target the intestine in order to control the development of atheromatous plaques.

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Schizophrenia and gut-brain axis

Chronic inflammation in the brain is suspected in schizophrenia.  Disruptions in the gastrointestinal microbiota and the immune system may also be involved.

The gut microbiota
Actu GP : Schizophrénie et microbiote : un lien confirmé ?

Schizophrenia affects around 0.7% of the world’s population. This psychiatric disease is characterized by delirium and hallucinations, social isolation, and psychological disruption. Onset is most often in adolescence or young adulthood, between ages 15 and 25.

The gut-brain axis involved?

Schizophrenia is very often accompanied by gastrointestinal disorders. In fact the likelihood of experiencing psychiatric diseases such as schizophrenia may be related to chronic intestinal inflammation involving the immune system. The origin may be an imbalance in the intestinal microbiota (intestinal flora) that favors this inflammation. Disruptions in the microbiota have been found in schizophrenic patients, associated with an increase in intestinal permeability (bacteria and other substances that pass into the blood stream through the intestinal wall). These studies seem to indicate a key role played by the gut-brain axis in the development of the disease.

Acting on the composition of the microbiota

With these results, prevention and treatment options emerge: one of them being rebalancing the microbiota to reduce chronic inflammation. Studies have shown that the administration of probiotics can have anti-inflammatory properties by affecting the immune reaction, although to date, no treatment of this type has demonstrated its effectiveness on schizophrenia.

Sources

Inserm. Schizophrenie, dossier d'information réalisé avec Marie-Odile Krebs, Mai 2014

Severance EG, Gressitt KL, Stallings CR, et al. Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia. Schizophr Res. 2013;148(1-3):130-137.

Ellul P, Fond G, « Focus sur la schizophrénie : infections, auto-immunité et dysbiose intestinale », L'information psychiatrique, 2016/10 (Volume 93), p. 797-802.

Sherwin E, Sandhu KV, Dinan TG, Cryan JF. May the Force Be With You: The Light and Dark Sides of the Microbiota-Gut-Brain Axis in Neuropsychiatry. CNS Drugs. 2016;30(11):1019-1041.

Nemani K, Hosseini Ghomi R, McCormick B, et al. Schizophrenia and the gut-brain axis. Prog Neuropsychopharmacol Biol Psychiatry. 2015;56:155-160.

Severance EG, Yolken RH, Eaton WW. Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling. Schizophr Res [Internet]. Elsevier B.V. 2014.

Severance EG, Prandovszky E, Castiglione J, Yolken RH, et al. Gastroenterology issues in schizophrenia: why the gut matters. Curr Psychiatry Rep. 2015 ; 17(5):1–10.

Caso JR, Balanzá-Martínez V, Palomo T, et al. The Microbiota and Gut-Brain Axis: Contributions to the Immunopathogenesis of Schizophrenia. Curr Pharm Des. 2016 ; 22(40):6122-6133.

Dickerson FB, Stallings C, Origoni A, et al. Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial. Prim Care Companion CNS Disord. 2014;16(1):PCC.13m01579.

Joseph J, Depp C, Shih PB, et al. Modified Mediterranean Diet for Enrichment of Short Chain Fatty Acids: Potential Adjunctive Therapeutic to Target Immune and Metabolic Dysfunction in Schizophrenia? Front Neurosci. 2017 Mar 27;11:155.

Tomasik J, Yolken RH, Bahn S, et al. Immunomodulatory Effects of Probiotic Supplementation in Schizophrenia Patients: A Randomized, Placebo-Controlled Trial. Biomark Insights. 2015 Jun 1;10:47-54.

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Mood disorders

Depression and bipolar disorder indicate a mood disorder. Beyond classic psychiatric treatments, research is in progress to evaluate the impact of intestinal microbiota on these disorders.

The gut microbiota

Mood disorders are common: 300 million people in the world suffer from depression and 60 million have bipolar disorder.These disorders cause mental distress that can often be severe, which can lead to suicide. They are the #1 cause of professional and social disability in the world.

Inappropriate stress response

Each individual has their own vulnerability to depression or bipolar disorder, which is in part genetic.As a result, during unpleasant life events, some people experience an excessive response, with overly elevated secretion of the stress hormones cortisol and adrenaline. This situation can lead to nervous exhaustion and favor the onset of a depressive state. Recent research has also documented the role of intestinal flora (microbiota) in these inappropriate stress responses. Indeed in animals, microbiota participates in the regulation of emotions through communication between the intestine and the brain. In the case of dysbiosis (disruptions in the composition of the microbiota), this regulation is less effective and favors the onset of mood disorders.

A new avenue for treatment

Beyond classic treatments (antidepressants, mood regulators, psychotherapy, etc.), a new avenue is opening: rebalancing the microbiota to influence mood. A recent study also showed that taking probiotics daily, a combination of lactobacilli and bifidobacteria, improved mood and reduced the level of anxiety in healthy subjects.

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Anxiety disorders

Certain anxiety disorders, which a great number of people suffer from, may be linked to activity in the gastrointestinal microbiota through the regulation of stress hormones. The discovery of the role of the microbiota in anxiety disorders allows us a glimpse of new potential avenues for treatment.

Anxiety disorders, which include phobias, generalized anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress, are characterized by both physical symptoms (tremors, palpitations, digestive spasms) and mental symptoms (anxious anticipation, hypervigilance, etc.). Fourteen percent of the European population is affected by this illness.

Microbiota activity as a regulator

The gastrointestinal microbiota plays a role in regulating anxiety symptoms related to stress through the microbiota-gut-brain axis. Recent data from humans in good health confirms hypotheses formulated with mice, suggesting that the microbiota influences mood and anxiety.

Stomach-brain paths of interaction

Intestinal microbiota-brain interactions involve the neurological pathway, through the activation of the vagus nerve and the onset of anxious signs (a knot in the stomach), and the blood, through the transportation of molecules from the intestine to the brain. The relevant molecules have several origins: bacterial molecules able to cross the lining of the brain (meninges), molecules secreted by intestinal cells (neuropeptides), and pro- or anti-inflammatory molecules (cytokines) produced by the intestine’s defense system.

New avenues for treatment

Beyond traditional treatment for anxiety disorders (psychotherapy, phytotherapy, anxiolytics, etc.), connections between the gastrointestinal microbiota and the brain are opening new avenues for treatment, such as probiotics, which aim to change the composition of the microbiota. However, the clinical effectiveness of this approach still remains to be proven.

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"Good question!" - Sherrie Miranda (From My health, my microbiota)

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Autism-spectrum disorders

Autism-spectrum disorders (ASDs) refer to the collection of neurobiological diseases that affect social interactions. They may have a gastrointestinal origin.

Actu PRO : Autisme : découverte d’un nouveau lien avec le microbiote intestinal

ASDs include autism, of course, but also Asperger syndrome, Landau-Kleffner syndrome, and PDD-NOS (pervasive developmental disorder not otherwise specified).

Boys affected 4 times as much as girls

Around the world, autism-spectrum disorders affect around one child in 160,2 and affect boys 4 times as often as girls. In spite of the diversity of the disorders, ASDs have characteristics in common: communication problems, alterations in social relationships, limited interests, and behavioral problems.

Indicative signs to watch for

Certain indicative signs should lead to consultations: a child who is indifferent to the sounds around them, who does not point with their finger, who avoids eye contact, who doesn’t react to separations or reunions, whose motor activities are limited and repetitive, etc. Only a specialist can suggest or eliminate an ASD diagnosis and help you tailor treatment.

Causes still unknown

Although the causes of autism-spectrum disorders remain unknown, researchers have closely studied the causes related to genetic or environmental factors. Clinical studies have, furthermore, shown the existence of dysbioses in autistic children,5 associated with a change in metabolic activity in the intestinal microbiota.

No treatment to date

This discovery leads to the idea that correcting imbalances in the digestive ecosystem could improve behavioral anomalies in ASDs and open new therapeutic perspectives. Clinical studies targeting the biological connections between autism and intestinal microbiota are being evaluated. To date, no medication cures autism-spectrum disorders; treatment tailored to the child’s needs can, however, considerably improve their quality of life.

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"Thx for awareness" - Marge OBrien (From My health, my microbiota)

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Parkinson's disease

Parkinson’s disease is the second most common neurodegenerative disease in France. It progressively destroys the dopamine neurons in the brain. A link to a disruption in intestinal microbiota has been shown.

The gut microbiota

Parkinson’s disease affects 1% of people over 65 in France, which represents about 100,000 people. The substantia nigra in the brain, the area that controls movement, loses the neurons that produce dopamine. The result is progressive motor symptoms: slowness in movements, muscle rigidity, and tremors. People who have Parkinson’s also face non-motor problems, like sleep problems, depressive episodes, and incapacitating gastrointestinal problems (constipation, bloating, abdominal pain, nausea).

Age is implicated

The primary risk factor is obviously age. Although genetic predispositions have been proven, no single one is sufficient to explain the disease. Environment is also a factor, with pesticides playing a documented role.

Gut-brain communication

Intestinal microbiota participates in communication between the intestine and the brain. Some researchers have hypothesized that chronic intestinal infection by Helicobacter pylori could be the origin of Parkinson’s disease. However, it hasn’t been determined whether the infection triggers the disease or, on the contrary, the disease promotes the infection.
Dysbiosis, meaning a fault in the composition of microbiota, has been highlighted in patients with Parkinson’s disease. They have fewer “anti-inflammatory” bacteria and more “pro-inflammatory” bacteria than healthy people.

Controlling progression and testing

Treatment focuses on limiting the motor symptoms of the disease (tremors, rigidity, etc.) through the use of dopamine precursors. These treatments don’t prevent the progression of the disease, and complications reappear after 5 to 10 years of treatment. Currently, the primary goal is to detect the disease as early as possible and slow down neural degeneration. Manipulating microbiota is one option currently being studied.

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Alzheimer's disease

Alzheimer's disease, whose factors are still poorly understood, still has no effective treatment.  However, a hypothesis around the role of the intestinal microbiota is emerging, sparking hope for new therapeutic avenues.

Alzheimer's disease, which affects more than 35 million people around the world, is associated with memory loss, language and comprehension problems, attention and concentration problems, apraxia (loss of dexterity), and, in some cases, agnosia (problems recognizing objects or faces). Added to these cognitive symptoms, which worsen over time, are behavioral symptoms such as anxiety, apathy, irritability, sleep problems, disinhibition, and agitation.

Causes still unknown

Several genetic and environmental risk factors have been identified for the disease: hypertension, hypercholesterolemia, smoking, sedentary lifestyle, unbalanced diet, and lack of cognitive stimulation, among others. Lesions in the brain are also a well-known component of the disease, particularly the accumulation of amyloid beta plaques and neuron degeneration. However, the causes of the disease have yet to be clearly determined.

The hypothesis of intestinal microbiota

Researchers are considering whether the intestinal microbiota is involved in Alzheimer’s disease: certain proteins (amyloid peptides) produced by “negative” bacteria in the intestinal flora may favor the development of the disease. Conversely, “beneficial” bacteria may play a protective role, by slowing the formation of amyloid plaques.

Break the therapeutic deadlock

Intestinal microbiota could represent a new avenue for therapeutic research, as no current curative therapy exists for Alzheimer’s disease. Only a few medications lessen symptoms, and their effectiveness is very limited. Some researchers are, therefore, considering carrying out future work on the disease via the microbiota, through dietary changes or by ingesting probiotics.

 

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Prostatitis and microbiota

Prostatitis is acute or chronic inflammation of the prostate. It can be caused by infection, in the case of acute inflammation. The responsible bacteria is most often Escherichia coli. Chronic pain, however, more likely implies an imbalance in the urinary microbiota.

The urinary microbiota
Prostatitis

Prostatitis affects around 10% of men. Symptoms, like in cystitis in women, include a burning sensation when urinating and the frequent need to urinate. Other symptoms may be present, such as pelvic, perianal, or rectal pain, and fever, which requires emergency treatment.

Acute prostatitis: an infectious origin?

The main bacteria responsible, Escherichia coli or other enterobacteria, come from the intestinal microbiota. Escherichia coli bacteria are implicated in 80% of cases of acute prostatitis. The infection most often starts in the urethra, which is the tube coming from the bladder. Sexually transmitted bacteria, like chlamydia or gonococci, can also cause prostatitis.

Urinary microbiota involved in chronic forms

In the case of chronic prostatitis, the origin is less clear; the bacteria are less frequently isolated. Recent studies suggest that an alteration in the urinary microbiota could play a role in the appearance of chronic prostatitis. In fact, we had long believed that urine was sterile, which is not the case. There is such a thing as the urinary microbiota. Furthermore, there is a difference in the composition of the urinary microbiota between patients with chronic prostatitis and that of healthy men. Modification of the urinary microbiota via antibiotic treatment may be the cause of chronic forms.

Antibiotic treatment

Treatment of acute prostatitis is based on the prescription of antibiotics and sometimes requires hospitalization in the event of serious symptoms. Treating chronic prostatitis remains more complicated. Probiotic options are still at a very preliminary stage.

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Cystic fibrosis

Cystic fibrosis is a rare genetic disease that manifests through serious respiratory and digestive problems. There appears to be a connection between these symptoms and the gastrointestinal microbiota.

The ENT microbiota

An estimated 105,000 people have been diagnosed with CF across 94 countries. France was the first country to introduce systematic testing at birth.

Alteration in the CFTR protein involved

Cystic fibrosis is caused by a change in the CFTR protein (Cystic fibrosis transmembrane conductance regulator), resulting from a mutation in its gene. The normal CFTR protein regulates exchanges of water and mineral salts across cell membranes. When it is defective, it leads to an increase in the viscosity of the mucus, causing it to accumulate in the respiratory and digestive tracts. This accumulation provides a foundation for bacterial infections in the respiratory tract and can eventually lead to respiratory failure. On the digestive side, cystic fibrosis leads to pancreatic insufficiency that affects digestion, the absorption of nutrients, growth, and presents with alternating diarrhea and constipation.

Imbalance in the microbiota

An imbalance in the intestinal microbiota may be associated with respiratory symptoms of cystic fibrosis. This dysbiosis, observed before the onset of the first signs, may be aggravated by the disease and accompanying antibiotic treatments. It contributes to undernutrition, growth delays, and, more generally, to digestive and respiratory complications in these patients.

Reducing symptoms

Treatment for these patients is given in specialist centers; its specific goal is to clear out the bronchi using bronchial decongestants and bronchodilators, combined with sessions of respiratory rehabilitation. Every three to four months, preventative antibiotic treatment is prescribed. Digestive problems are treated with a hypercaloric diet, supplemented with pancreatic extracts and vitamins.

In the future, new therapeutic strategies that aim to have an impact on the microbiota during the first weeks of life through nursing or the use of probiotics could delay the onset of respiratory damage, reinforce these patients’ immune systems, and, as a result, reduce the morbidity and mortality associated with cystic fibrosis.

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Winter respiratory infections

Cold, bronchitis, strep throat... It’s hard to get through the winter without being affected by at least one of these respiratory infections. In terms of prevention, probiotic therapy may stimulate immune defenses.

The pulmonary microbiota

Winter diseases, which are most often viral, sometimes have clinical signs very similar to the flu (Influenza virus), which is why they’re called influenza-like illnesses or flu-like symptoms.

Flu-like symptoms, often confused with flu

Flu-like symptoms include some or all of the following symptoms: fever < 38.5 C, chills, cough, fatigue, muscle ache, sore throat, headaches, runny nose, etc. Only blood tests can confirm infection with the influenza virus.

An overburdened immune system

Intestinal immune defenses protect you from attacks by pathogenic agents like bacteria and viruses. However, in winter, the immune system is attacked more often. We spend more time confined, and rooms are less well-aired. As a result, more circulating microbes are transmitted (exhaled air, coughs, sneezing).

Probiotic therapy being studied

The viral nature of winter respiratory infections immediately excludes the use of antibiotics. Treatment is symptomatic: acetaminophen, together with hydration and rest, is the basis of the medical prescription.
The use of probiotics has also been proven to be effective in clinical studies on winter respiratory diseases. The daily use of probiotics for several months reduced fever, runny nose, and coughing. It also led to a reduction in the prescription of antibiotics and the number of sick days.

"Taking a prebiotic and a probiotic is useful . A healthy gut is a healthy immune system." - Sharon Smerek (From My health, my microbiota)

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