The skin microbiome may not be the only one involved in the severity of atopic dermatitis: the nasal microbiome may also play a role. Although distinct, these two microbiomes are nonetheless linked.
Changes in the skin microbiome have been associated with atopic dermatitis (AD) and its severity. The nasal microbiota may also be involved: Staphylococcus aureus has been found five times more often in the nose of AD patients. The nostrils may be an important source of self-contamination and of bacterial propagation from the nose to the skin, or vice versa. A study has therefore focused on the relationship between skin and nasal microbiomes in children with AD, based on the severity of the disease.
Nose and skin: two connected microbiomes?
Using 16S-rRNA sequencing, the researchers first found distinct microbial communities in the nose (89 samples) and on the damaged skin (57 samples) of children with AD: while the nasal microbiome was dominated by Actinobacteria (Corynebacterium spp.), Proteobacteria (mainly Moraxella) and Firmicutes (Staphylococcus, Streptococcus and Dolosigranulum spp.), the skin lesions were dominated by staphylococci, and to a lesser extent by species belonging to the genera Pelomonas, Streptococcus and Janthinobacterium. However, correlations were found between the bacterial species in the nose and those on the skin, although the mechanisms involved are not fully understood (cross-transmission between the two niches?).
Microbiomes linked to disease severity
Most importantly, the compositions of the nasal and skin microbiomes, and particularly that of the skin microbiome, were both found to be linked to the severity of pediatric AD. This was so even after adjusting for confounding factors such as age, antibiotic use, and skin sample site. This link between the microbiomes and AD severity is mainly due to the presence of staphylococci in both niches, and of other species, such as Moraxella in the nose.
Distinguishing between bacterial presence and bacterial load
The study also showed that S. aureus was present in the skin lesions of one out of two patients–more often in (sidenote:
Trend nevertheless statistically insignificant
)–but that its load (measured by quantitative PCR) was not associated with the severity of AD. Conversely, although the presence of S. epidermidis in the skin was not correlated with severity in 80% of the samples, its load was significantly higher in cases of severe AD. Even though this association does not demonstrate a causal link, the results suggest that the two microbial niches play a role in exacerbating inflammation caused by the disease. Hence the importance of exploring in future studies not only the role of microbial species in AD and their relationships with the host and other species, but also the interactions between the different microbial communities within the organism.
A new study supports the theory of a link between gut dysbiosis and autism spectrum disorders (ASD), whose worldwide prevalence continues to grow but whose etiology remains unknown.
A strong weight of evidence supports the hypothesis of a link between gut dysbiosis and autism. For example, many ASD patients suffer from gut imbalances–such as a deficiency of Bifidobacterium longum and an excess of Clostridium spp. and Candida albicans–, which are thought to be associated with inflammation of the gut and increased permeability of the gut-blood barrier. In addition, gastrointestinal comorbidity and digestive enzyme deficiencies are more common in children with ASD. Despite this, the mechanisms involved and the contribution of the gut microbiota to the development of ASD remain poorly understood.
A novel pairing strategy
However, a decisive step forward may now have been taken. In a study published in Science Advances, a research team compared the gut microbiota of 39 children with ASD to that of 40 neurotypical children of the same age and gender. This first analysis revealed differences in 18 bacterial species between these two groups but could not explain the exact role of the gut microbiota in the development of the disease. To control for interindividual diversity of the microbiota, the researchers developed a strategy consisting of pairing each ASD patient to a control subject based on the metabolic profile of their microbiota. A novel cohort of 65 pairs was thus created, with a metagenomic analysis performed to identify the metabolic pathways that differed between the two groups.
Impaired intestinal microbial detoxification
Among the 96 metabolic pathways associated with ASD, five that are involved in intestinal detoxification were significantly deficient compared to the control subjects, as were 8 enzymes involved in the degradation of toxins contained in insecticides and food additives. The authors believe that these detoxification impairments in ASD children may contribute to mitochondrial dysfunction, which can affect all tissues, including brain tissue. Based on these data, the researchers constructed a diagnostic model capable of discriminating ASD children from control subjects with 88% accuracy.
Increased gut permeability
This finding may explain why children with ASD are so vulnerable to environmental toxins and suggests that the impaired gut detoxification process in ASD patients may be involved in the development of the disease. However, the reasons for deficiencies in microbial detoxification remain unclear. One hypothesis points to a gut dysbiosis which, by causing increased intestinal permeability, allows environmental toxins to enter the bloodstream. Among other effects, these toxins may alter the mitochondria in the brain. If confirmed, this hypothesis could pave the way for new therapeutic strategies aimed at restoring the microbial detoxification capabilities of ASD patients, according to the authors.
A major medical discovery of the 20th century, antibiotics have saved millions of lives, but their excessive and often inappropriate use has led to the emergence of multiple forms of antibiotic resistance. This past November, the WHO publicly highlighted the importance of using antibiotics prudently.
The use of antibiotics increased by 65% between 2000 and 2015. This new study reminds us that when eradicating pathogenic germs responsible for infections, antibiotics can also destroy beneficial bacteria in the gut microbiota, thereby causing an imbalance (dysbiosis) within this ecosystem, with potential short and long-term consequences.
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If you are interested in the effects of antibiotics on your health and your microbiota, or if you want to know more about the World AMR Awareness Week (WAAW), we recommend that you go to this other dedicated page:
Adverse effects on microbiota in the short and medium term...
The first thing to note is that antibiotics disrupt the balance existing in the gut microbiota. By eliminating certain bacteria, they allow other pathogens to occupy the free space and multiply. One consequence is antibiotic-associated diarrhea, which affects between 5% and 35% of patients but usually resolves spontaneously within a few days. However, some forms of diarrhea can be more severe and when caused by Clostridioides difficile they may even be fatal.
The second observation is that antibiotics are linked to a reduction in microbiota diversity. A return to equilibrium may take some time, with certain bacteria still absent after several months. Lastly, the repeated or inappropriate use of antibiotics leads bacteria to develop strategies to circumvent their effects. Bacteria can become antibiotic-resistant, thereby rendering treatments ineffective. The experts’ predictions are unsettling: unless drastic measures are taken to address the issue, the misuse of antibiotics could cause ten million deaths worldwide by 2050.
+65%
The use of antibiotics increased by 65% between 2000 and 2015.
5% - 35%
Antibiotic-associated diarrhea affects between 5% and 35% of patients.
...with serious long-term consequences
Systemic use of antibiotics is still far too widespread among infants and children and is thought to be associated with the development of diseases later in life (obesity,asthma, allergies, inflammatory bowel disease). This battle is far from won and the scientific community is actively seeking new strategies to restore the gut microbiota, based on multiple modulation pathways (diet, probiotics, prebiotics).
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 study has shown that the risk of oropharyngeal disturbance increases among hospitalized patients with the length of hospitalization and the use of certain treatments. The study points to the gut bacteria as the most common cause of imbalance.
The oropharyngeal microbiota (OM) normally comprises a wide variety of bacteria that help maintain a balanced local environment. Some illnesses and drugs such as proton pump inhibitors (PPIs) can disturb this balance, thereby allowing opportunistic pathogens to colonize the oropharyngeal tract. Microaspiration of these pathogens during hospitalization can lead to colonization of the lower respiratory tract, increasing the risk of nosocomial pneumonia. Early detection of oropharyngeal disturbance may be a means to reduce incidence. A team of researchers studying the occurrence of the disturbance during hospitalization has identified patient characteristics associated with the disorder.
Oropharyngeal disturbance increases with length of hospital stay
Oropharyngeal samples were collected from 134 hospital patients within 24 hours of admission, on day 3 of hospitalization, and then every four days for the remainder of their stay. The samples were analyzed by conventional bacterial culture and MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry, with the pathogens then classified into three categories: respiratory tract pathogens, gut microbiota species and yeasts. In 89% of the patients, the swab collected at admission showed a balanced OM. The authors found that a significant proportion of patients developed an OM disturbance during their stay, and that the number of patients with the disorder increased with the length of stay.
Antibiotics and PPIs responsible for disturbance
The prescription of antibiotics during hospitalization appears to be associated with this imbalance. Similarly, PPI and antibiotic use prior to hospitalization are predictive of an OM disturbance consisting of colonization by bacterial species from the gut microbiota. The study found that the risk of nosocomial pneumonia increased in patients treated with PPIs or antibiotics prior to hospitalization. Conversely, patients admitted to hospital on a short-term basis had a lower risk of oropharyngeal colonization by gut pathogens. These results underline the need for vigilance in the management of patients with risk factors associated with OM disturbance. Patients admitted to hospital with ongoing antibiotic or PPI treatment may well benefit from more aggressive physiotherapy aimed at maximizing lung aeration and minimizing aspiration. In this way, early detection of an OM disturbance may reduce the incidence of nosocomial pneumonia.
Angiotensin converting enzyme 2 (ACE2) is the key receptor for SARS CoV-2, the virus responsible for the Covid-19 pandemic. Its expression on the luminal surface of the gut has led researchers to investigate its exact role, as well as the impact of Covid-19 on the gut microbiota and gut epithelium.
While Covid-19 usually produces respiratory symptoms, a significant proportion of patients suffer from gastrointestinal disorders such as diarrhea, vomiting or abdominal pain. In a review of 35 studies involving 6,686 Covid-19 patients, 29 of the studies showed a 4% prevalence of gastrointestinal symptoms and a 19% prevalence of liver function abnormalities. These symptoms were more severe with increased viral load. In addition, approximately 10% of patients had gastrointestinal symptoms only, and no respiratory symptoms.
A deregulation of ACE2 in the gut
To link bowel disorders to Covid-19, the researchers investigated the role of ACE2 (receptor for the SARS CoV-2 (sidenote:
The Spike protein, or S protein, is the key that allows SARS-CoV-2 to enter human cells
)) in gut inflammation. Highly expressed in the gut, its function is to control the absorption of dietary amino acids such as tryptophan, which plays an important role in immunity. Indeed, several preclinical studies suggest that gut ACE2 is an essential regulator of gut inflammation. In an (sidenote:
ACE2 knockout mouse
An ACE2 knockout mouse is a mouse model in which the ACE2 gene is absent
) mouse model, the absence of the ACE2 gene leads to more (sidenote:
A sodium dextran sulphate (DSS)-induced colitis model
). In another model (animals treated with an (sidenote:
Angiotensin receptor blocker (ARB)
)) with stress-induced inflammation, increased ACE2 expression correlated with reduced inflammation. Therefore, an ACE2 deficiency increases gut’s susceptibility to inflammation.
A lasting gut dysbiosis?
Furthermore, the digestive tract takes longer to excrete SARS-CoV-2 than the respiratory tract. SARS-CoV-2 RNA persists in the stool in over half of patients even after a negative nasopharyngeal swab test and up to 33 days after symptomatic healing of a lung lesion. A study on 15 patients also showed persistence of gut dysbiosis well beyond infection, with a loss of beneficial species in most patients. Exposure to SARS-CoV-2 may therefore be associated with long-lasting harmful effects on the gut microbiota.
According to the authors, by down-regulating gut ACE2, SARS-CoV-2 may modify the gut microbiota and increase systemic inflammation, which may explain the multiple organ failure observed in Covid-19.
Fusobacterium nucleatum levels in tumors may predict poorer responses to chemotherapy and act as a marker for poor prognosis in esophageal cancer. Could this lead to new antibiotic therapies targeting this bacterial species?
As the sixth leading cause of cancer death, esophageal cancer remains highly lethal, with five-year survival rates of 15%-20%. Esophageal squamous cell cancer (ESCC) is the most common subtype of the disease. Current treatments include (sidenote:
Neoadjuvant chemotherapy
To reduce tumor size prior to surgery
) (NAC) followed by esophageal resection. Although patients who respond favorably to NAC have a better chance of survival, most tumors develop NAC resistance. Understanding the mechanisms behind NAC resistance is therefore key to improving treatment response and, accordingly, patient survival.
What role does Fusobacterium nucleatum play in tumors?
The composition of the gut microbiota has already been shown to influence responses to certain cancer treatments such as immunotherapy and chemotherapy. In addition, intratumoral Fusobacterium nucleatum levels have recently been shown to be associated with reduced survival and/or increased recurrence rates in colorectal cancer and in ESCC. This encouraged researchers to assess, for the first time, the prognostic value of intratumoral F. nucleatum levels in ESCC patients and their ability to predict NAC response. The study was carried out in 551 Japanese subjects from two independent cohorts.
Predictive marker of reduced survival rate...
First finding: tumor tissue has higher levels of F. nucleatum compared to adjacent healthy tissue. In addition, intratumoral F. nucleatum levels are associated with both the stage of tumor progression and a reduction in relapse-free survival (RFS). The link between F. nucleatum and reduced survival is observed even in early-stage patients, suggesting that this bacterial species may promote tumor aggressiveness. Intratumoral F. nucleatum levels may therefore serve as a prognostic biomarker.
... and poor responses to chemotherapy
Lastly, analyses in a subgroup of 101 patients receiving NAC showed that patients with increased levels of F. nucleatum had a lower response to tumor treatment. Although the mechanisms likely to explain the role of F. nucleatum in increased tumor resistance remain speculative (activation of metabolic pathways leading to cell autophagy?; deactivation of chemotherapeutic substances?), the researchers point out a promising therapeutic avenue: improving responses to chemotherapy via an antibiotic therapy targeting F. nucleatum. More work to follow.
Diet, pollution, urbanization... many factors influence the composition of our various microbiota and are potentially linked to the increased prevalence of non-communicable diseases. In response, exposure to green spaces allows new microorganisms to colonize our microbiota, potentially to their benefit.
The microbial world present in the air, soil and plants is considered critical for our health. Certain theories suggest that low exposure to green spaces and to the microorganisms found in them has contributed to the contemporary rise in obesity, diabetes mellitus, and allergies. Therefore, a better understanding of the interactions between man and nature, and especially between microbiota and environment, seems key to fighting these non-communicable diseases. To this end, a team of scientists evaluated the impact of green spaces on the composition and diversity of the skin and nasal flora of three individuals following visits to urban green spaces in three different countries, Australia, India, and the UK.
Green spaces increase microbial diversity
During their walks, the participants took soil, leaf, and air samples in order to analyze the bacteria in the environment. They also took samples from their nose and skin before and after each exposure to the environment so as to assess the impact of green spaces on their microbiota. The analysis revealed that the skin flora had changed following the walk: it was richer in bacteria, more diverse and closer to that of the soil, evidence that environmental bacteria had colonized the skin. Furthermore, the composition of the nasal microbiota was similar to that of air samples.
Transient changes?
Even more interesting was the overall similarity between the changes in microbial diversity and composition in the three countries visited, even though many factors known to influence the composition of the microbiota, such as pollution, humidity, or diet, differed between these three countries. It is not yet known how long these changes in the flora last, but previous studies suggest that most environmental bacteria transferred to humans disappear after 2 hours, with less common types potentially persisting for up to 24 hours on the skin. Further research is required to establish whether there are any health benefits from these microbial changes, but in the meantime, feel free to roll around in the grass!
Selway CA, Mills JG, Weinstein P, et al. Transfer of environmental microbes to the skin and respiratory tract of humans after urban green space exposure. Environ Int. 2020 Dec;145:106084.
In a large study, a Dutch team compared the impact of 15 antibiotic classes on the composition of the gut microbiota up to four years after prescription.
As part of World Antimicrobial Awareness Week (18-24 November 2020), the WHO encouraged the general public, health workers and decision-makers to adopt best practices in order to avoid the emergence and spread of antimicrobial resistance. While antibiotics were one of the major therapeutic advances of the 20th century, they can also have an adverse impact on the body’s various microbiota. Although the short-term effects of some classes of antibiotics on the gut microbiota are well known, the long-term effects are not yet fully understood. This study compared the impact of 15 classes of antibiotics on the composition of the gut microbiota up to four years after the last dose.
“Large scale” study
The composition of the gut microbiota of 1413 participants (median age: 62.6 years) who had previously taken antibiotics was analyzed by 16S rRNA sequencing. The time elapsed from the last dose of antibiotics to the day of sampling was categorized as follows: 0-12, 12-24, 24-48 and >48 months. The results were adjusted for certain confounding factors (sex, age, BMI, diabetes mellitus, concomitant medications such as statins, PPIs, corticosteroids, etc.).
Hailed as one of the greatest medical advances of the 20th century, antibiotics have saved millions of lives. But they also have an impact on our microbiota by inducing a dysbiosis. Let’s take a look at this ambivalence role:
The most significant and prolonged impact on the gut microbiota was observed for macrolides and lincosamides: decrease in Shannon ratio that lasted for 4 years after the last administration, and significant change in bacterial community structure (Bray-Curtis diversity ratio). A significant loss of diversity was also observed one year after use of beta-lactams.
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.
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.
Impact of antibiotics with high anti-anaerobic activity
The results also revealed that antibiotics with high anti-anaerobic activity (penicillin/beta-lactamase inhibitor combinations, imidazole derivatives and lincosamides) had a greater and longer-lasting impact on the gut microbiota than other classes: the Firmicutes/Bacteroidetes ratio significantly shifted in favor of Firmicutes up to one year after administration, while this ratio significantly shifted in favor of Bacteroidetes up to two years after taking antibiotics with no anti-anaerobic activity.
Therefore, macrolides and lincosamides are associated with an acute and long-lasting dysbiosis of the gut microbiota. These effects differ in strength and duration depending on the class of antibiotic used. According to the authors, these findings should be considered when prescribing antibiotics.
Is it unrealistic to train machines to “read” stool samples and help diagnosing cardiovascular disease? No, according to a recent study which found this original approach to be almost as effective as existing diagnostic techniques and, more importantly, much less time-consuming.
Cardiovascular disease (CVD) is the world’s number one cause of death. By 2030, CVD-related deaths are expected to peak at 23.6 million. Its diagnosis currently involves a series of time-consuming and costly examinations (clinical tests, ECG, chest X-rays, echocardiogram). An alteration (dysbiosis) of the gut microbiota has been linked to several types of CVD, including hypertension, heart failure and atherosclerosis. So why not use artificial intelligence to design a diagnostic test for CVD based on gut microbiota composition?
CVD “signatures” present in the stool
Machine learning is a branch of artificial intelligence that involves inputting data into a computer so that it can learn how to solve a problem. In healthcare, it has been successfully used to diagnose and predict various diseases, such as cancer, diabetes mellitus and inflammatory bowel disease. To test its usefulness for diagnosing CVD, a team of researchers compared different analytic algorithms and sought to identify characteristic “signatures” for the disease in stool samples obtained from 478 patients with CVD and 473 healthy subjects. They found significant differences between the two groups in the relative intestinal abundance of 39 bacteria.
Strong diagnostic capacity
The researchers identified a specific algorithm which, by targeting 25 bacterial families within the gut microbiota, could discriminate between the two groups with 70% accuracy. This level of accuracy is only slightly below that of the conventional approach, which is able to diagnose 76% of CVD patients, but requires an array of clinical data (age, gender, smoking status, blood pressure, cholesterol levels, etc.). According to the authors, the use of machine learning to identify intestinal dysbiosis characteristic of cardiovascular disease has very promising diagnostic potential in the context of routine check-ups.
Aryal S, Alimadadi A, Manandhar I, et al. Machine Learning Strategy for Gut Microbiome-Based Diagnostic Screening of Cardiovascular Disease. Hypertension. 2020 Nov;76(5):1555-1562.
Fecal transplant involves introducing a healthy person’s stool into a patient’s digestive tract in order to reconstruct their intestinal flora and help them fight pathogenic bacteria.
The equilibrium between “good” and “bad” microbiota bacteria can be disrupted by many different phenomena. This imbalance, known as (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.), can cause many diseases of varying severity. Fecal transplant (also called fecal bacteriotherapy) is a possible therapeutic solution.
Fecal transplant: a centuries-old solution
Fecal transplant is a very old treatment, since it was already being carried out in China in the 4th century! Its effectiveness was only recognized by European learned societies in 2013. To date, it has only been indicated in recurring C. difficile pathogenic bacteria infections, which it cures in 90% of cases.
However, the involvement of microbiota in numerous other diseases (Inflammatory Bowel Diseases, diabetes, obesity, neuropsychiatric disorders, etc.) suggests that indications for fecal transplant could soon be expanded.
The procedure
Once selected, the donor prepares by taking laxatives. Their stool is then diluted in a sterile solution and filtered to be administered to the recipient. The recipient ingests a preparation similar to that used for colonoscopies in order to eliminate the disrupted microbiota.
There are several administration routes for the stool: the introduction of a probe through the nose to the stomach or duodenum, colonoscopy, enema, or, more rarely, ingestion of gastro-resistant capsules. It is up to the patient to decide with their doctor which route best suits their situation.
The only validated indication for FMT is recurrent Clostridioides difficile infection. This practice may present health risks and must be performed under medical supervision, do not reproduce at home!
The Biocodex Microbiota Institute is dedicated to education about human Microbiota for General Public and Healthcare Professionals, it doesn't give any medical advice.
We recommend you to consult a healthcare professional to answer your questions and demands.
