By attacking commensal bacteria as well as pathogens, antibiotics disturb the balance of the gut flora. These collateral effects are well known. However, little is known about the specific activity of each class of antibiotics on the different bacterial species of the gut microbiota. A study published in Nature1 has filled in the gaps.
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.
Antibiotics are an extraordinary scientific discovery that saves millions of lives but their excessive and inappropriate use has now raised serious concerns for health, notably with antibiotic resistance and microbiota dysbiosis. Let’s take a look at this dedicated page:
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.
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.
The study thus sheds new light on the activity of antibiotics while indicating promising strategies to reduce their adverse effects on the gut microbiota.
Depression, psychosis, anorexia, etc. The proof of disturbances of the gut microbiota in different psychiatric disorders are accumulating. Even so, is there a common signature or conversely are there specific characteristics for all these disorders? A meta-analysis takes stock.
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 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.
Nevertheless, these results should still be interpreted cautiously, as confusion factors (taking of psychiatric medicines, diet, etc.) could bias the results.
Cereals, pulses, berries... These are the frugal meals we imagine on our European ancestors’ tables. However, an analysis of their gut microbiota, via human feces preserved for over three thousand years in Austrian salt mines, reveals that they also had blue cheeses and beer on their plates.
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 (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 (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 (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.
According to a new study published in Gut, a signature that associates serum metabolic profile with the gut microbiota could be used as a new tool for early, reliable, and non-invasive diagnosis of colorectal adenomas and cancers.
Imbalances in the microbiota (dysbiosis) have been associated with numerous diseases, including diabetes mellitus, obesity, neuropsychiatric or neurodegenerative disorders, and even cancer. Metabolites produced by the gut bacteria enter the bloodstream early. With this in mind, a new study has sought to establish the profile of serum metabolites linked to the gut microbiota. The goal? To find a serum metabolite signature associated with the gut microbiota in people with colorectal cancer (CRC) or adenomas. This non-invasive, accurate, and rapid detection method would allow the early diagnosis of these conditions.
Metabolomic alterations at all levels
The analysis of serum samples from a discovery cohort (31 healthy individuals, 12 patients with adenoma and 49 with CRC) identified 885 serum metabolites whose relative abundance differed between adenoma or CRC patients and healthy individuals. We know gut microbiota alterations in patients with colorectal anomalies can reprogram the fecal metabolome; but can they reprogram the serum metabolome? To determine the potential of these markers to predict colorectal anomalies, the researchers performed an analysis of serum and fecal metagenomic metabolites of the gut microbiota in 11 healthy individuals and 33 abnormal colorectal patients. 322 metabolites were found to be associated with the gut microbiota, including species known to be associated with CRC onset and progression (Fusobacterium nucleatum, Parvimonas micra, etc.). An algorithm was then used to accurately identify 8 serum metabolites that distinguished the healthy individuals in the cohort from those with adenomas and CRC (area under the curve 0.96). These metabolites were selected as a predictive panel for colorectal disease: gut microbiome-associated serum metabolites (GMSM).
Towards a predictive model?
This model was tested on a modeling cohort (72 healthy individuals and 120 with colorectal disease) and an independent validation cohort (53 healthy individuals and 103 abnormal colorectal patients) and reliably distinguished adenoma and CRC patients from healthy individuals (area under the curve 0.98 and 0.92, respectively). Lastly, this model was compared to other commonly used detection methods, the carcinoembryonic antigen (CEA) test and fecal occult blood test (FOBT). The GMSM panel was superior to the CEA in discriminating patients from healthy individuals in the validation cohort (area under the curve of 0.92 vs 0.72), and also beat the FOBT in discriminating between the two groups (sensitivity 83.5% vs 65.2%).
The gut dysbiosis observed in patients with CRC is thus associated with alterations in serum metabolites. The identification of these markers in serum is promising and paves the way for an early and non-invasive detection of patients with adenomas or CRC.
Microbiota imbalances have been shown in many psychiatric illnesses such as schizophrenia, depression or obsessive compulsive disorder (OCD). But does each illness have “its” dysbiosis or are there common microbial changes? A review of studies takes stock.
Many studies have been conducted throughout the world recently to identify the special characteristics of disturbances in the gut microbiota of people suffering from mental illnesses. Is their intestinal flora less rich than that of people in good health? Less diversified? Are some species of micro-organisms very well represented? Or conversely are they missing? The stakes are high because if specific characteristics associated with one or more mental illnesses are found in different studies, they could serve as useful markers for the diagnosis of patients, the treatment strategy or the assessment of the response to treatments. However, up to now, these studies provide results that are still contradictory.
Imbalances common to several psychiatric illnesses
A publication in (sidenote:
JAMA
Journal of the American Medical Association) Psychiatry is gaining ground by reviewing nearly 60 studies performed on this subject. The objective of its authors is to confirm that mental illnesses are indeed associated with disturbances of the gut microbiota and to determine if these are specific to each illness:
Scientists have observed a significant reduction in the richness of the gut microbiota of patients with mental disorders, but little difference in the diversity of species in comparison with the microbiota of participants in good health. Instead of demonstrating specific characteristics for each illness, these studies rather show similar imbalances of the intestinal flora shared by several mental disorders. In particular, these disturbances result in the increase in certain species promoting inflammation and the reduction of other species with an anti-inflammatory action in bipolar disorders, schizophrenia and anxiety.
Confusion factors to be taken into consideration
Finally, the review has made it possible to determine the factors responsible for the variations of results between the studies. On the one hand, the geographical area: diet, so the microbiota and the imbalances in the microbiota are not the same in China as they are in Western countries. On the other hand, the taking of medicines: psychotropic drugs seem to favour dysbioses. Researchers must, therefore, keep these parameters in mind to be able to unveil all the mysteries of the link between the gut microbiota and mental illnesses, for the benefit of patients.
The scourge of our century, nearly 40 million children under the age of 5 were either overweight or obese in 2019, according to the WHO1. The focus is placed on diet and physical activity to prevent childhood obesity and reinstate the energy balance equilibrium. These are necessary but not sufficient. Now hope has turned to the gut microbiota, a key player in metabolism and communication with the brain. Deciphering.
40 millions
nearly 40 million children under the age of 5 were either overweight or obese in 2019
Microbiota and obesity: dysbiosis in the hot seat
The gut microbiota, a real ecosystem lodged in our gut is essential for our health. As far as obesity is concerned. it is now known that a lack of diversity in the gut microbiota and the over-representation of some species of bacteria increases the risk of adiposity, insulin resistance and inflammation. So obese patients would have flora that is less rich than that of thin people even though the results are not yet unanimous.
Microbiota and obesity: risk factors
Apart from genetic factors, there are other factors that contribute to the development of obesity in children: The mother's diet during pregnancy, the method of giving birth, nutrition of the newborn (breast or bottle feeding), antibiotic treatment during childhood, etc. The biological mechanisms by which these possible risk factors will influence the development of obesity have not yet been clearly determined. However, the microbiota is suspected and a special interest is taken in it.
Microbiota and obesity: scientifically proven
It is obvious that obesity is a multi-factorial disease. It is therefore too early to raise an exclusive cause and effect link between the microbiota and obesity in humans. However, this link has been proved in animals where studies have shown that the “obese” characteristic can be transmitted from an “obese” donor mouse to a “thin” receiver mouse by faecal microbiota transplantation and vice versa.
Microbiota and obesity: personalise our diet for better prevention
It is obvious that our diet has an influence on the composition of our microbiota. The child's microbiota will develop during the first years of life. It reflects his/her living environment and diet. For researchers, this period of life is important for carrying out dietary interventions. How? Via prebiotics which are naturally present in food and which the bacteria adore, and also due to probiotics, which are micro-organisms that we can ingest directly.
Adapting diet depending on the specific nature of one's microbiota. This new approach would provide better prevention of the risks of obesity from childhood onwards. And should this personalised diet become an ally of weight in the fight against obesity, a worldwide scourge which has almost doubled in the space of half a century1? The range of possibilities - and hope - remains open...
Antibiotics are commonly used among breast cancer patients, to prevent opportunistic infections for instance, or during periods of immunodeficiency. The researchers in this study show, in a mouse model of breast cancer, that antibiotics may accelerate tumor growth by inducing imbalances in the gut microbiota.
The gut microbiota has been linked to disease progression in several cancers. However, there is limited research detailing its influence in breast cancer. At the same time, antibiotics have an impact on the bacterial population of the gut microbiota. Antibiotic use is common among cancer patients, despite controversy surrounding the benefits. Accordingly, a study evaluating the effect of antibiotics on the gut microbiota and their impact on the clinical course of breast cancer was overdue. A recent study in a mouse model published in iSciences has filled the gap.
Accelerated tumor growth and microbiota depletion in mice receiving antibiotic treatment
Both before and after injection with breast cancer-specific tumor cells, mice were given a cocktail of antibiotics: vancomycin, neomycin, metronidazole, amphotericin, and ampicillin (VNMAA). Compared to the control group, these animals rapidly exhibited significantly accelerated tumor growth and strong depletion of the gut microbiota.
The researchers then focused on the effects of an antibiotic widely used in breast cancer patients: cephalexin. Although cephalexin had a smaller impact on the microbiota than the VNMAA cocktail, it caused a similar increase in tumor growth.
Anti-tumor role of certain gut bacteria
In the mice undergoing antibiotic treatment, metagenomics revealed a dysbiosis which, while not favorable to pathogenic bacteria, adversely affected protective bacteria. Animals treated with VNMAA and cephalexin had a lower relative abundance of bacteria thought to play an anti-tumor role: Lactobacillus reuteri, Lachnospiraceae bacterium, and Faecalibculum rodentium. By simply reintroducing the latter bacteria, the previous level of tumor growth was restored.
Mast cells, drivers of tumor growth in dysbiosis
Antibiotic-induced microbiota disturbances do not have a significant impact on the tumor immune microenvironment. However, they do increase the number of mast cells in the tumor stroma.
The researchers treated both control and VNMAA-treated mice with cromolyn, a mast cell stabilizer. While cromolyn inhibited tumor growth in the antibiotic-treated mice, it had no effect on the controls. These data suggest a potential role for mast cells in breast cancer progression in individuals with antibiotic-induced dysbiosis.
Even though this study was performed on a mouse model, it opens up new perspectives for the treatment of breast cancer. It is now necessary to identify what causes the increase in mast cells, what changes occur in mast cells as a result of microbiota disruption, what causes these changes, and how it causes them.
Chemotherapy has significantly improved the overall survival rate of people with cancer. At the same time, the (sidenote:
More than 87% of chemotherapy patients report at least one adverse event.
) related to treatment still have a major impact on patients’ physical (vomiting, diarrhea, constipation, fatigue, hot flushes, etc.) and psychological (depression, insomnia, cognitive disorders, etc.) well-being. Moreover, chemotherapy also suppresses immune responses and increases the incidence of infection and subsequent morbidity and mortality. The gut microbiota is suspected of being associated with both the efficacy and adverse effects of chemotherapy, although few data are available. Hence this literature review, which examined 17 studies ( (sidenote:
5 studies on colorectal cancer, 3 on acute myeloid leukemia, 2 on non-Hodgkin lymphoma, 1 on breast cancer, 1 on lung cancer, 1 on ovarian cancer, 1 on liver cancer, and the remaining 3 on various other types of cancer.
)) on the relationship between the gut microbiota, chemotherapy and chemotherapy’s side effects.
Microbiota, efficacy and toxicity of chemotherapy
Of the 17 studies reviewed, 7 were observational. Of these, 3 assessed the relationship between the gut microbiota, chemotherapy efficacy, and chemotherapy adverse events using fecal samples collected before treatment. Four other studies assessed the relationship between the gut microbiota, chemotherapy, and adverse events using fecal samples collected post-treatment. The results? The gut microbiota is associated with both the effectiveness of chemotherapy and the occurrence of adverse events.
The ten other studies were prospective (allowing causal links to be examined) and analyzed the impact of chemotherapy on the gut microbiota (risk of infection, diarrhea, etc.) using multiple stool samples taken before, during and/or after treatment. The conclusions? Chemotherapy modulates the gut microbiota of cancer patients. This modulatory effect is associated with an increased risk of infection and impacts the effectiveness of the treatment. In addition, the dysbiosis induced by chemotherapy appears to be related to the adverse events.
Biomarker and modulator
These results have significant implications: the gut microbiota may serve as a biomarker to predict the outcome and adverse effects of chemotherapy, while modulating the gut microbiota during treatment may reduce adverse effects and improve treatment efficacy. These hypotheses are supported by previous studies involving lifestyle interventions such as prebiotics and exercise.
This review of the complex relationships between the gut microbiota and chemotherapy highlights the potential for future research to improve patient care. Further results will require international multicenter trials that control for the various confounding factors (age, ethnicity, gender, co-morbidities, drug use, geography, diet, physical activities, etc.).
