No more age- or weight-based triaging for Covid-19 patients admitted to the hospital. In the future, measuring the abundance of two bacterial species in the oropharyngeal microbiota could become the gold standard, thanks to its superior reliability. These are the claims made by a German team who believe this microbiota plays a crucial role, since it regulates host immunity, homeostasis of the mucous membranes, and defense against pathogens. However, previous studies have been less conclusive. Most likely because the majority focused on patients with severe Covid-19, where numerous intervening factors (e.g., antibiotic therapy, invasive mechanical ventilation, etc.) could also have altered the diversity and composition of the microbiota samples.

When antibiotics and ventilation disrupt the oropharyngeal microbiota 

This cross-sectional, multi-center clinical study (7 German centers) therefore adapted its methodology: oropharyngeal swabs were taken from 72 healthy adults, 112 patients with non-SARS-CoV-2 infections (mild upper respiratory tract infections or critical pneumonia), and patients with mild, moderate or severe Covid-19 (n=36, 37 and 65). The total study population was 322 participants aged 21 to 93 years.

The results? Broad-spectrum antibiotics and invasive mechanical ventilation appear to destabilize the oropharyngeal microbiota: there is a loss of diversity and severe dysbiosis in Covid-19 patients admitted to the hospital with moderate or severe disease, or when the sampling is performed during prolonged hospitalization.

Two bacterial species can predict mortality

The most important finding was that samples harvested promptly after admission (to avoid alteration due to hospital care) have a signature predictive of Covid-19 mortality, according to artificial intelligence models (machine learning). A lower abundance of two bacterial genera, Neisseria (and more specifically the species Neisseria subflava) and Haemophilus (species Haemophilus influenzeae, parainfluenzae and pittmaniae) considerably increase the risk of death. And this predictive model is more reliable than models based on clinical variables such as age, sex, or obesity. The underlying mechanisms have not yet been explained, but it is possible that these bacteria regulate innate immune response and cytokine production.

Tuberculosis is a highly contagious infectious disease that affects over 10 million people around the world (sidenote: Tuberculosis_WHO Oct 2021 )  (WHO, Oct 2021). Although cases are becoming rarer in developed countries thanks to vaccination programs, tuberculosis remains a major public health problem. What is more, the Covid-19 pandemic has reversed years of progress worldwide in the fight against tuberculosis, and for the first time in over a decade, the tuberculosis death rate has risen, according to the 2021 World Health Organization (WHO) Global Tuberculosis Report (sidenote: Tuberculosis deaths rise for the first time in more than a decade due to the COVID-19 pandemic _WHO Oct 2021 ) . Much collateral damage is being sustained by the microbiota in our gut and lungs, which are heavily involved in this infection.

Disruptions to the gut microbiota 

The first microbiota in the line of fire is our intestinal flora, which works closely with our immune cells throughout our lives. Tuberculosis stops this microbiota from operating at full capacity; it loses its diversity and certain bacteria begin to dwindle, while others become more abundant. This imbalance of certain bacterial species (dysbiosis) could even be characteristic of the stages of disease progression.

In addition, based on results from animal models, these disruptions to the gut microbiota make tuberculosis drugs less effective. Hence the idea, not yet validated, of restoring balance to the gut microbiota using probiotics and postbiotics (sidenote: Postbiotics A preparation of inanimate microorganisms and/or their components that confers a health benefit on the host. Salminen S, Collado MC, Endo A, et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol. 2021 Sep;18(9):649-667. ) . The aim is to increase the efficacy of the tuberculosis drugs and strengthen the patient’s immune defenses against the bacteria responsible for TB.

Intestinal and pulmonary troops uniting against infection

Although in different locations, the gut and lung microbiota do not appear to work in isolation. These two microbiota communicate closely and their diversity changes in tandem: the gut microbiota contributes to the pulmonary immune response, and the lung infection in turn affects the composition of the gut microbiota. They are therefore not just two microbiota, but an intestinal/pulmonary unit with a role to play in TB infection and treatment. This could therefore justify a new treatment approach.

Recommended by our community

Have you ever heard the word “dysbiosis”? Or about the benefits of probiotics for your health? Did you know that your gut microbiota is a good indicator of longevity? Or that your vaginal microbiota consists of hundreds of bacteria that help maintain a healthy vaginal environment? Curious and experts, will find the answers to these questions. 

A hub designed around three major health topics, built around personalized journeys:

Information written by scientists about Microbiota become accessible for everyone through news, physician interviews, thematic folders, infographics, developed content and even through stories on the mobile version. 

About the Microbiota Institute 

The Biocodex Microbiota Institute is an international scientific institution that aims to foster health through spreading knowledge about the human microbiota. To do so, the Institute addresses both healthcare professionals and the general public to raise their awareness about the central role of this still little-known organ of the body. 

^BMI-21.47

Available in 7 languages (English, French, Spanish, Russian, Polish, Turkish, and Portuguese), this online international hub offers you the latest scientific news and data about microbiota including the Institute’s exclusive content such as Microbiota magazine, thematic folders, continuing medical education (CME) courses and interviews with experts. 

A useful and trustful partner for HCPs 

In a dedicated section for HCPs, you will also find practical and educational infographics such as: “What are probiotics?” or “what you need to know about the 6 microbiota of the human body?”, that you can easily download and share with your patients. Care to share other information with your patients? Invite them to discover the lay public section of the website through dedicated online journeys, where they can find updated, useful and understandable content. 

Stay tuned, stay up to date! 

Also available on this hub, congress calendars where you can find the next events about microbiota. And after your journey on the website, don’t forget to register online to receive the “Microbiota Digest”, a monthly newsletter with the latest news about microbiota. Want to share a publication? To follow a Conference live-tweet (WGO, ESPGHAN, etc.)? Or browse through Microbiota Institute’s new Twitter account (@Microbiota_Inst) designed to reach the widest community of health professionals who want to be up to date with the latest information on the microbiota field. By providing healthcare professionals with the latest scientific news and data, but also a variety of educational tools and services, Biocodex Microbiota Institute’s website aims to help healthcare professionals improve their patient’s understanding of their conditions on an everyday basis. 

About the Microbiota Institute 

The Biocodex Microbiota Institute is an international scientific institution that aims to foster health through spreading knowledge about the human microbiota. To do so, the Institute addresses both healthcare professionals and the general public to raise their awareness about the central role of this still little-known organ of the body. 

^_BMI-21.46 

Searching for a link between the gut microbiota and autism has been a hot topic in recent years. It is true that the gut is our “second brain” and that some neuropsychiatric conditions such as depression are associated with imbalances in intestinal flora. Moreover, mice transplanted with intestinal bacteria from people with autism develop “autistic behavior.” This population is also prone to digestive problems. It may therefore seem an obvious step to assume that autistic spectrum disorders are due to changes in the gut microbiota, and that autism can be treated by rebalancing the gut.

Dysbiosis and autism: an exaggerated link?

However, Australian researchers believe this is one step too far, despite some studies that appear to show characteristic changes to the gut microbiota in autistic children. Having looked at all publications on this topic, they believe that there is no evidence of a causal link between the intestinal flora and autism. With differing protocols, often based on small population sizes, and rarely accounting for “confounding” factors such as diet that can also alter the intestinal microbiota, and inconsistent in their microbial analysis results... these studies do not, according to this new review, make a convincing argument.

These researchers rolled up their sleeves and conducted a vast study of the intestinal microbiota in 247 children (99 diagnosed with autism and 148 not). They analyzed the bacterial species present in the samples, also taking into account stool consistency and other factors known to alter the gut microbiota such as diet, sex, and age. They concluded that an autism diagnosis is not significantly associated with the composition of the intestinal microbiota.

Intestinal flora disruptions due to a lack of variation in the diet

On the other hand, the study revealed that the composition of the intestinal microbiota in these autistic children was very strongly correlated with diet, stool consistency, and age. A narrower range of interests and repetitive behavior are typical traits of autism. Many autistic children prefer to eat the same food at every meal, or are put off by certain tastes, smells and textures, explains one of the authors.

These results suggest therefore that autism leads to a less varied diet (and therefore one of poorer quality), resulting in a loss of diversity in the gut microbiota and, in turn, softer stools. Widely reported in the media, this article goes against the tide of theories about a link between the gut microbiota and autism. Nevertheless, the authors believe that nutritional measures could help rebalance gut microbiota in autistic children and relieve their gastrointestinal disorders, while also improving their overall health.

Recommended by our community

For several years, the scientific community has shown a keen interest in the possibility of a link between gut microbiota and autistic spectrum disorders. There is clearly an increasing volume of evidence of associations between the gut microbiota and certain neuropsychiatric conditions. Moreover, mice studies appear to have shown that fecal transplantation from autistic patients triggers “autistic behaviors.” Finally, people with autism commonly suffer from gastrointestinal disorders. Spurred on by this array of evidence, several teams have sought to highlight the major role, perhaps even a causal one, that intestinal dysbiosis might play in autism. This would allow us to better understand, diagnose, and even treat autistic spectrum disorders by targeting the microbiota.

Dysbiosis and autism: an exaggerated link?

However, by looking at all the studies and meta-analyses already conducted on this topic, an Australian research team believes that this conclusion is somewhat premature. With differing methods, often based on small population sizes, subject to certain bias and rarely accounting for confounding factors such as diet and age, and inconsistent in their microbial analysis results... these studies do not, according to this team, make a convincing argument.

The researchers therefore conducted a metagenomics study of the intestinal microbiota in 247 Australian children (99 diagnosed with autism and 148 not). Their analysis included several other factors known to alter the gut microbiota such as dietary, clinical, genetic, psychometric, and demographic elements. They found that the composition of the gut microbiota of these children showed only negligible differences between the autism and non-autism groups. Only an abundance of the species Romboutsia timonensis appears to be linked to autistic spectrum disorders. In addition, they were unable to reproduce the results of studies claiming to have established a link between certain microbiota species (e.g., Prevotella and Bifidobacterium) and autism.

Lack of microbiota diversity associated with a lack of variation in the diet

On the other hand, the study did find changes in the composition of the gut microbiota of autistic children that correlated with diet, stool consistency, and age. Certain autistic traits, such as a narrower range of interests, repetitive behaviors, and clear sensory preferences, could affect their diet. According to the research team, autism leads to a diet that is less varied, and therefore of poorer quality. This contributes to a reduced diversity of the intestinal microbiota, which in turn results in softer stools indicative of digestive problems.

Widely reported in the media, this article goes against the tide of theories about a link between the gut microbiota and autism. However, the authors believe that dietary measures could help rebalance gut microbiota in autistic children and thus relieve their gastrointestinal disorders while improving their general health.

Some are morning people, others prefer the evening. But what makes us an early bird or a night owl? Recent scientific research suggests that bacteria in the gut may influence our biological clock, with early birds and night owls shown to have very different gut microbes.

Early to bed vs. late to bed: specific microbiota

An analysis of the gut microbiota of 91 individuals has shown a greater abundance of the bacterial genus Alistipes in the gut microbiota of early sleepers. These people generally have bowel movements in the morning, eat a healthy diet (rich in fruit, vegetables, and fiber), and drink water regularly.

On the other hand, night owls have a greater quantity of Lachnospira in their gut. They go to the toilet in the evening, following a day of unhealthy food (e.g. rich in sugars) washed down with soda. The bacteria in our digestive tract produce molecules that act on our own body. These molecules cause a set of chemical reactions (known as metabolic pathways) which lead to the production of certain compounds (e.g. glucose) and/or the degradation of others. Three metabolic pathways were found to be significantly more common in early sleepers.

The authors therefore propose that certain human metabolic pathways are activated by specific bacterial fatty acids involved in the regulation of our sleep. This may be the missing link between all these data: a given diet has a specific microbiota, which secretes molecules that influence the rhythm of the host’s sleep.

Improving night owls’ health

The scope of these observations is important, going beyond the mere issue of harmony in families with both early and late sleepers. Indeed, night owls are more likely to develop:

...and other chronic diseases.

This research suggests it may be possible to improve their health by altering their diet and, therefore, their gut microbiota. This may help the night owls go to bed with the early birds.

Drugs have a major impact on the microbiota. In particular, antibiotics attack both pathogenic and commensal bacteria. They are known to modify the balance of the flora and cause digestive disorders such as diarrhea and Clostridioides difficile infection. In the longer term, they can contribute to allergies and metabolic disorders. To understand more precisely how different classes of antibiotics disturb the balance of the gut microbiota, German researchers analyzed the effects of 144 antibiotics on the growth and survival of 27 commensal microorganisms, including several species of Bacteroides.

Three bacteriostatic antibiotics with bactericidal action 

By analyzing 815 combinations of antibiotics and commensal species, the researchers were able to observe the different behaviors of antibiotics according to their class. For example, from first- to fourth-generation quinolones the spectrum of activity broadened, with the latter inhibiting almost all the commensal species tested, while macrolides inhibit all species except C. difficile. Eight out of nine tetracyclines inhibit almost all commensal species, which is surprising since the gut microbiota is considered a reservoir of tetracycline-resistant genes. Even more surprising was that erythromycin, azithromycin, and doxycycline, although classified as bacteriostatic, showed a rapid bactericidal effect on 12 commensal species in almost half of cases. The decrease in survival, of more than 99.9%, was confirmed by a viability test on Bacteroides vulgatus and a strain of Escherichia coli.

Antidotes to minimize impact of antibiotics on commensal bacteria 

These observations challenge the long-standing distinction between bactericidal and bacteriostatic antibiotic classes and provide a possible explanation for the strong effect that macrolides have on the gut microbiota. However, the researchers did not stop there. They also screened their database of 1,200 drugs to find whether any had an “antidotal” effect against the bactericidal activity of erythromycin and doxycycline on commensals, without preventing the activity of these antibiotics against pathogens. Fifteen drugs were found to be of interest. The scientists tested them at different concentrations on a synthetic microbial system and on an animal model containing twelve commensal species. The result: ten drugs strongly protected commensals, the most powerful of which were dicoumarol, benzbromarone, and two non-steroidal anti-inflammatory drugs, tolfenamic acid and diflunisal.

Can mental health be assessed via alterations in the gut microbiota? If so, do these biomarkers make it possible to distinguish between this various disorders? Yes and no is the conclusion from a meta-analysis of 59 control case studies based on 8 psychiatric disorders, the most represented of which were depression, schizophrenia, psychosis, bipolar disorders and anorexia. Though there are biomarkers in the gut microbiota signalling mental disorders, no specific characteristics have emerged in the light of the analysed data.

Little effect on the richness of the microbiota…

To arrive at this result the authors have performed comparisons between groups depending on the relative abundance of the intestinal bacteria, in the light of:

• alpha diversity (sidenote: α diversity A measurement indicating the diversity of a single sample, i.e. the number of different species present in an individual. Hamady M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010 Jan;4(1):17-27. ) (34 studies) 
• and beta diversity (sidenote: β diversity A measurement indicating the diversity of species between samples. It makes it possible to evaluate the diversity of the microbiota between subjects. Hamady M, Lozupone C, Knight R. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 2010 Jan;4(1):17-27. ) (43 studies).

Alpha diversity was significantly reduced only in patients presenting bipolar disorders. Furthermore, no significant difference was noted in the diversity indices measuring both diversity and distribution evenness between the species present, namely the Shannon (reported in 29 studies) and Simpson (reported in 11 studies) indices. 

Regarding beta diversity, the results show similar differences in the phylogenetic structure in patients suffering from depression and psychosis/schizophrenia compared with the controls. However, the authors note that the method for classifying patients, based on symptoms or diagnosis, could affect this result.

…But changes in the composition of populations

This study also notes relatively constant dysbioses in patients, such as:

• reduction in Faecalibacterium (in 15 out of 17 studies reporting this genus),
• reduction in Coprococcus (10 studies out of 10),
• and enrichment in Eggerthella (10 studies out of 11).

Microbial biomarkers and psychiatric disorders: no conclusion that is too hasty

The authors therefore conclude that there are common microbial disturbances in depression, bipolar disorders, anxiety, psychosis and schizophrenia: 

• impoverishment in anti-inflammatory bacteria producing butyrate and 
• enrichment in pro-inflammatory bacteria.

A shared signature that could open the door to transdiagnostic therapy focussed on these similar dysbioses.

Bones, pottery, weapons, textile fragments... The treasures unearthed by archaeologists during excavations allow us to better understand the lifestyles of our ancestors. Feces are also a precious source of information, helping us understand what our ancestors ate. In some archaeological sites, such as the underground salt mines of Hallstatt in Austria, prehistoric human excrement, or “paleofeces”, have survived since the Iron Age, safe from degradation.  These mines provide a wealth of information on the diet, health, and gut microbiota of our distant ancestors. This encouraged a team of Italian and Austrian researchers to take a closer look at some samples.

Microbiota reveals “non-Westernized” diet persisted until Baroque period

The microscopic study of four stool samples (sidenote: Foor stool samples One sample from the Bronze Age, two from the Iron Age, and one from the Baroque period. ) revealed that the diet of our European ancestors was based on cereals (barley, spelt, millet, etc.), pulses, wild fruits (apples, blueberries), and nuts. A DNA analysis of the bacteria in the stools showed that their gut microbiota was similar to that of populations that follow a non-Westernized diet based on unprocessed food products, fruits, and vegetables. The researchers believe that this type of diet lasted until the eighteenth century in Europe, after which a more modern lifestyle, the Western diet (sidenote: Western diet The Western diet is characterized by an excess of sugars, certain fats, processed foods, and environmental pesticides, and by a lack of fiber. It has been associated with obesity and certain inflammatory and metabolic disorders, such as type 2 diabetes mellitus, insulin resistance, and inflammatory bowel disease.
Siracusa F, Schaltenberg N, Villablanca EJ, et al. Dietary Habits and Intestinal Immunity: From Food Intake to CD4+ T H Cells. Front Immunol. 2019 Jan 15;9:3177. ) , and medical advances altered the gut microbiota.

Roquefort cheese already popular with gourmets nearly 3,000 years ago 

One of the Iron Age samples caused astonishment among the scientists. It was exceptionally rich in DNA from two species of microorganisms (sidenote: Microorganisms Living organisms that are too small to be seen with the naked eye. They include bacteria, viruses, fungi, archaea and protozoa, and are commonly referred to as “microbes”. What is microbiology? Microbiology Society. ) : Penicillium roqueforti and Saccharomyces cerevisiae. These two yeasts are still used today, the first to make blue cheeses and the second to make beer, wine, and bread. This shows that “processed foods” already existed in Iron Age Europe. 

It was already known that our Iron Age ancestors produced beer, but the researchers feel that the presence of blue cheeses demonstrates the sophistication of ancient European culinary traditions. Salted with natural salt, inoculated with yeast in wooden vats, the cheeses seem to have matured in ideal conditions as regards temperature and humidity. The recipe still works for the Roquefort cheese we eat today.