What causes Autism Spectrum Disorders (ASD)? The question has puzzled the scientific community for decades. While the gut cannot fully explain the causes of ASD (characterized by difficulties in socializing and communicating, or even obsessive-compulsive disorders (OCD)), it may provide some of the answers. These answers are to be found in the billions of bacteria and other microorganisms that populate the gut microbiota, for better or worse.

Gut disorders and ASD: a dangerous liaison

Since ASD was first described in 1943, numerous symptoms have been identified. Gut disorders (diarrhea, constipation, irritable bowel, etc.) are among the most standard physical symptoms. Children with ASD experience three to four times more gastrointestinal disturbances than the norm. Severe autism often goes hand in hand with the most severe gut disorders–and vice versa. In fact, researchers have even shown that autistic patients show an improvement in behavior following treatment of a gastrointestinal disorder. They therefore became interested in the mechanisms behind these gastrointestinal disorders and took a closer look at the gut microbiota.

A microbiota that believes itself to be the brain

Observation no. 1: autistic patients often present an altered gut flora (dysbiosis) that is poor in beneficial bacteria and richer in microbes involved in certain gut disorders (diarrhea, constipation, etc.). Not content with troubling the gut, these microbes also produce “signal” molecules used by the gut and the brain to communicate. Produced to excess, these molecules could interfere with the communication process and lead to behavioral disorders such as those encountered in ASD.

A leaky gut?

Observation no. 2: the gut barrier no longer does its job, i.e., preventing microbes, allergens and other foreign molecules from entering the bloodstream. The immune system is activated as a result, triggering inflammatory reactions. Many autistic patients exhibit gut permeability, gut and neuronal inflammation and gut disorders associated with a response to heightened stress. These data suggest a strong gut-brain link in ASD. However, the mechanisms by which gastrointestinal disorders contribute to autism are extremely complex. Further research is therefore required to identify therapies to treat these gut problems and improve the quality of life of patients with ASD.

Lung cancer is the leading cause of death by cancer worldwide. While active tobacco use is the main risk factor, 25% of cases occur in non-smokers, a high percentage not fully explained by the major risks identified (passive smoking, pollution, family history, etc.). In addition to the gut microbiota, which is involved in the development of certain gastrointestinal cancers, other microbial ecosystems have also been associated with cancer risk. In this study, the authors investigated whether the oral microbiota’s composition and its ability to colonize the respiratory tract are involved in the development of lung cancer.

Depleted microbiota, increased risk

Their prospective study involved the long-term follow-up of more than 136,000 never-smoker Shanghai residents (61,500 men, 75,000 women), with follow-up visits every 2-3 years. A saliva sample taken at the outset was analyzed in all subjects reporting lung cancer and in an identical number of controls, matched for sex, age, date and time of sample collection, previous antibiotic treatment, etc. Metagenomic shotgun sequencing was then used to compare the 114 subjects diagnosed with lung cancer with the same number of controls. This analysis found a greater risk of developing lung cancer where the oral microbiota lacks bacterial diversity.

Greater abundance of Firmicutes is harmful

The inherent composition of the oral microbiome also appears to play a major role. Among the population studied, an increase in the relative abundance of Spirochaetes and/or Bacteroidetes was associated with a lower risk of lung cancer. Conversely, a greater abundance of bacteria belonging to the Firmicutes phylum, particularly Lactobacillales, was associated with an increased risk of lung cancer. The authors point out that these results coincide with those of previous studies showing a link between Firmicutes and certain respiratory diseases (chronic obstructive pulmonary disease or COPD, squamous cell carcinoma of the head and neck, and lung cancer).

ENT microbiota: further research required to clarify its field of action

This large-scale characterization of the oral microbiota sheds new light on the causes of lung cancer in non-smokers. The geographical homogeneity of the study reinforces the relevance of its findings but limits their scope. Further work on different populations and in different locations would help clarify the role of the ENT microbiota in the development of lung cancer and other respiratory diseases.

Crohn’s disease and ulcerative colitis are both forms of IBD and have one thing in common: they cause uncontrolled inflammation of the lining of a section of the digestive tract, resulting in various symptoms during inflammatory flares. While there is currently no cure for these diseases, there are treatments such infliximab (sidenote: Infliximab A biotherapy that neutralizes TNF-α, the protein responsible for tissue inflammation. ) (IFX) aiming at reducing inflammation. However, a third of patients do not respond to this therapy and there is currently no biomarker (sidenote: Biomarker An objectively measured biological characteristic that makes it possible to evaluate responses to treatment. This response can be complete or partial. )  that predicts response to treatment. The researchers in this study may have found the answer in the gut microbiota.

Gut microbiota differs before treatment...

Numerous studies have shown a link between the composition of the gut microbiota (bacteria and, more recently, fungi) and IBD. Therefore, in order to identify markers that predict response to IFX therapy, the researchers evaluated the impact of IFX treatment on the gut microbiota composition of 72 IBD patients (sidenote: 25 patients with Crohn’s disease (CD) and 47 with ulcerative colitis (UC). ) . Bacterial and fungal diversity in the gut microbiota was analyzed using fecal samples collected before treatment and 1 year after beginning of therapy. The patients were classified into three groups according to their response to treatment. The study revealed that the bacterial and fungal profiles of the three groups differed significantly before start of therapy.

...offering a predictive tool

Significant differences between the three groups of patients were also observed after initiation of treatment: non-responders had lower contents of anti-inflammatory bacteria and higher contents of pro-inflammatory bacteria and fungi (such as the genus Candida) compared with responders. These results suggest that the gut microbiota is involved in responses to treatment.

Based on these findings, the researchers subsequently identified certain bacteria and fungi present in the gut before start of treatment which could be used to predict responses to IFX therapy. Early identification of non-responders would permit rapid modification of treatment, limiting side effects and reducing the costs involved. A fully positive approach!

Theobroma cacao is the botanical name for the cacao tree; but did you know that Theobroma means “food of the gods” in Greek? Once reserved for priests and kings, chocolate has, fortunately, become more democratic. Today, it is consumed and appreciated throughout the world for its delicious taste and health benefits. With a cocoa content of more than 80%, dark chocolate is undoubtedly the most beneficial to health. For example, it contains specific compounds that could alleviate complications in chronic kidney disease (CKD).

Dark chocolate and gut microbiota: a winning combination?

The kidneys of patients with CKD have reduced functional capacity and no longer filter blood properly. This failure leads to an accumulation of molecules such as uremic toxins (sidenote: In total, more than 80 molecules are considered uremic toxins, among them hormones, peptides and even organic compounds. )  in the blood. These patients have an unbalanced gut microbiota (dysbiosis) that may contribute to the production of these toxins. Eating cocoa may modulate the gut microbiota by promoting the colonization by bacteria with known beneficial effects (Lactobacillus and Bifidobacterium) in the gut. A number of studies have also shown that, by modulating the gut microbiota, the ingestion of chocolate improves the integrity of the gut barrier, decreases inflammation and reduces uremic toxins.

Dark chocolate, the white knight of your cardiovascular system

Patients with CKD have a high risk of cardiovascular disease and premature death. Several studies have shown that the regular consumption of dark chocolate has a cardioprotective effect in healthy individuals. How so? By improving blood circulation, specifically, improving functioning of the blood vessels and reducing blood pressure. This improvement also leads to a reduced risk of stroke.

Munch on chocolate to boost your mood

We tend to forget that chronic illness often has a psychological impact on the patient. Beyond the simple pleasure of taste, the regular consumption of dark chocolate also stimulates the production of serotonin (a neurotransmitter involved in the regulation of behavior), which has an antidepressant effect. Although the consumption of dark chocolate (cocoa content of more than 80%) seems an interesting therapeutic alternative for patients with CKD, its potential impact on inflammation, cardiovascular risk and the gut microbiota has not yet been studied in a prospective clinical trial. But don’t let that stop you from treating yourself to a square of chocolate!

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Newborns subjected to antibiotic therapy reportedly exhibit an altered gut microbiota composition. However, the clinical or microbiological long-term consequences of this exposure remain unknown. Given the causal links between the intestinal microbiota and growth, obesity, and metabolic disease, researchers have suggested that neonatal antibiotic exposure might exert a long-lasting effect on childhood growth by disrupting the natural gut microbiota colonization process.

Altered development...

A study on 12,422 children born from singleton pregnancies at full term provided a host of information. The infants studied had no known growth abnormalities and did not require long-term prophylactic antibiotic treatment. 9.3% of the neonates in the study were exposed to antibiotics (sidenote: Combination of intravenous benzylpenicillin and gentamicin for most infants )  within the first 14 days of life. Among exposed newborns, only boys had significantly lower weights compared to non-exposed children throughout the first six years of life. They also exhibited a significantly lower height and body mass index (BMI) between the ages of 2 and 6 years. This result was confirmed in a German cohort of 1,707 children followed from birth to 5 years. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with a significantly higher BMI in both boys and girls.

...and a modified gut microbiota

To study the effect of neonatal antibiotic exposure on the gut microbiota, fecal samples were collected at the ages of 1, 6, 12, and 24 months from a separate group of 33 newborns, 13 of whom received intravenous benzylpenicillin and gentamicin within the first 48 hours of life. Twenty healthy newborns not exposed to antibiotics in the neonatal period were chosen as controls. The fecal microbiota was analyzed via 16S rRNA gene sequencing. Significant differences between the gut microbiota composition of the antibiotic-treated and control groups were observed after 1 and 6 months, demonstrating the persistence of the effect of antibiotic exposure on the microbiota. The genus Bifidobacterium was most substantially affected, with its content significantly reduced up to 24 months after antibiotic exposure.

Gut dysbiosis in question?

To establish whether causal relationships exist between neonatal antibiotic exposure, gut dysbiosis and child growth, the researchers conducted a complementary study in germ-free mice (sidenote: Germ-free mice mice that have no microbes at all, raised in sterile conditions. ) . The mice received a fecal microbiota transplant (FMT) with feces obtained from antibiotic-exposed children 1 month and 2 years after the antibiotic treatment. A significant reduction in weight gain was observed in male mice that received FMT from antibiotic-exposed infants, as compared to male mice that received FMT from non-exposed infants. In contrast, growth in female mice was not affected.

These findings suggest a causal link between exposure to antibiotics during the first six years of life and growth disorders during childhood which could be caused by the gut dysbiosis that appears during the development of the gut microbiota.

In recent years, many studies have examined the link between gut dysbiosis and depression, a condition that affects more than 300 million people worldwide. Two new studies have confirmed the gut microbiota’s role in the disease.

The endocannabinoid system: the link between depression and the gut microbiota

In a study carried out by the Pasteur Institute, CNRS and INSERM, naive mice received a fecal microbiota transplant (FMT) from either healthy mice or mice with depression induced by unpredictable chronic mild stress (UCMS). The researchers then analyzed the gut microbiota, the metabolism of polyunsaturated fatty acids and neurogenesis in the hippocampus (a brain region heavily involved in the development of depressive symptoms). According to the study, the symptoms of the UCMS mice (reduced hippocampal neurogenesis, mood disorders) had been transferred to the FMT mice. Metabolomic analysis of the FMT mice revealed an altered fatty acid metabolism characterized by deficits in lipid precursors of endogenous cannabinoids. This resulted in impaired activity of the brain’s endocannabinoid system, which is thought to have induced depression. Increasing endogenous cannabinoids, either via the pharmacological blockade of the enzymes that degrade them or through diet, reduced depressive symptoms in the mice that received the FMT from the UCMS mice. This increase in endogenous cannabinoids also led to a recovery in neurogenesis in the hippocampus of these mice. Lastly, a gut microbiota dysbiosis characterized by a decrease in Lactobacilli abundance was observed in both the UCMS (donor) and FMT (recipient) mice. Complementing the dietary intake of the FMT mice with a strain of Lactobacilli was sufficient to increase both endogenous cannabinoid brain levels and hippocampal neurogenesis, thus alleviating mood disorders. This work in mice provides a new mechanistic scenario for the gut microbiota’s involvement in depression via the endogenous cannabinoid system. The study also suggests that dietary interventions or the use of probiotics may be an effective means to fight against the symptoms of this disease.

Gut biomarkers: towards more accurate diagnosis?

In a second study, Chinese and American researchers identified 3 bacteriophages, 47 bacterial species and 50 metabolites whose fecal abundance differed between a first cohort of 118 patients with untreated major depressive disorder (MDD) and 118 healthy controls (HC). The analysis of a second, validation cohort (38 treated MDD patients vs. 38 HC) showed that 6 biomarkers (2 bacteria, 2 phages and 2 metabolites) made it possible to discriminate between MDD patients and healthy controls in both cohorts with an accuracy of more than 90%. Lastly, the researchers showed that levels of fecal GABA and its relevant metabolites were consistently decreased in MDD patients relative to HC. These findings suggest that fecal GABA levels in the patients with MDD may be modulated by a panel of gut microbes, which in turn may be collectively implicated in the development of MDD. These findings provide new directions to uncover the pathogenesis of MDD. They also help improve MDD diagnosis, which is currently incomplete and subject to misdiagnosis, by focusing on the gut microbiota.

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The gut microbiota is populated by various microorganisms which synthesize compounds called metabolites that are essential for the proper functioning of the human body. Over the last decade, researchers have established links between microbiota imbalances and various diseases, including major depressive disorder (MDD), a psychiatric disorder with significant social consequences. A recent study has confirmed this link and has gone one step further by using the gut microbiota as a diagnostic tool.

A more precise map of the microbiota

Lacking easily measurable biomarkers and based solely on patient interviews, MDD diagnosis is often incorrect or incomplete. In order to get an accurate picture of the gut microbiota in depression, the researchers studied bacteria, viruses, and their metabolites in the stool of a hundred MDD patients and a hundred healthy controls. They identified 3 bacteriophages (viruses that infect bacteria), 47 bacterial species and 50 fecal metabolites that showed notable differences in abundance between MDD patients and healthy controls. According to the researchers, these biomarkers may serve as a complementary tool in the diagnosis of depression, alongside clinical interviews. The analysis of a second cohort showed that these biomarkers made it possible to identify the MDD patients in both cohorts with an accuracy of more than 90%.

Gut-brain axis at the heart of depression?

This mapping also revealed that GABA (a neurotransmitter which decreases brain activity) was found in lower quantities in the stool of MDD patients. According to the researchers, this decrease may be modulated by the altered bacterial composition of MDD patients’ microbiota and may be involved in the development of MDD. The authors speculate that the decrease in gut GABA levels in MDD patients may be correlated with the dysregulation of GABA function in the brain. This hypothesis would seem to confirm the role of the gut-brain axis in major depressive disorder. The study therefore provides new hope for the diagnosis of MDD.

Despite their high fat and caloric content, avocados may help us lose weight. Their secret is their richness in fiber and monounsaturated fatty acids (MUFA), which increase satiety and reduce fat levels in the blood. But how does the consumption of avocados impact the bacteria in the gut microbiota and the products that result from the fermentation of ingested food, particularly in obese or overweight people (sidenote: Overweight is defined as a body mass index (BMI) of 25-30; obesity corresponds to a BMI of >30. ) ?

An avocado a day for three months

To answer this question, a team of researchers followed 157 adults aged 25 to 45 who were overweight (sidenote: Overweight is defined as a body mass index (BMI) of 25-30; obesity corresponds to a BMI of >30. ) or obese, but otherwise healthy, for 12 weeks. The subjects were divided into two groups. All were given a meal prepared by the researchers once a day, instead of breakfast, lunch, or dinner. Only one group received a meal containing an avocado, the caloric content of which was matched in the other group. With the exception of the avocado, meal ingredients were >90% similar. For their other meals, the participants were instructed to maintain their usual eating habits and daily serving sizes.

More fat in the stool, less in the body

Results: participants in the avocado group reported MUFA (“good fat”) consumption that was ~20 g higher than the control group, while dietary fiber consumption was 14 g higher. The participants also had a daily caloric surplus of 300 kcal. Despite this, by the end of the study, they had not put on a single ounce. At the same time, their gut microbiota had diversified and was enriched in bacteria able to break down fiber. In addition, their stool contained diminished bile acid concentrations (molecules secreted by the digestive system which make it possible to absorb fats) and more fats. The authors conclude that by modifying the gut microbiota, avocados influence the host metabolism and increase fat excretion. They are already considering new dietary approaches to improve the health of the increasing number of overweight or obese people.