To mark the WHO's annual World Antimicrobial Awareness Week, The Biocodex Microbiota Institute takes stock.

Accredited training on dysbiosis and the impact of antibiotics 

A folder dedicated to the impact of antibiotics on microbiota 

Infographics to share with your patients

Impact of antibiotics on the microbiota: experts' corner 

All the latest news on the impact of antibiotics on microbiota 

To mark the WHO's annual World Antimicrobial Awareness Week, The Biocodex Microbiota Institute takes stock.

Antibiotic resistance and resilience of the gut microbiota

Prof. Harry Sokol sheds light on

Antibiotic resistance: research advances

Prof. Sørensen sheds light on it

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The latest news on antibiotic resistance

How can we solve the problem of antibiotic resistance?

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Osteoporosis, which affects nearly 30% of women over the age of 50, is a major public health problem characterized by bone weakening likely to lead to repeated fractures. The mechanisms involved in this disease are not fully known, but a growing number of studies suggest that inflammation could increase the risks.

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Gut microbiota: still an underexplored avenue

We know that certain microorganisms in the gut and vaginal microbiota can modulate the immune response and impact the inflammatory system. Could they be implicated in osteoporosis? This is what researchers from the University of Zhengzhou in China tried to find out.

They enrolled 132 women between the ages of 45 and 70, all menopausal for over a year, and divided them into 3 groups based on their bone density: “no bone problems,” “slightly decreased bone density” and “osteoporosis”. The scientists collected stool and vaginal secretions from all of these female volunteers to analyze and compare their vaginal and gut microbiota. 

Results: The microbiota of women with osteoporosis have different compositions than those of the other two groups, and this difference is particularly visible at the gut level (1).

Inflammation-promoting bacteria 

The gut flora of women affected by osteoporosis was richer in bacteria whose presence is associated with a lower level of interleukin IL-10, a molecule with anti-inflammatory properties, and also in bacteria associated with the production of “pro-inflammatory” cytokines that contribute to bone destruction.

On the other hand, it was poorer than the others in bacterial species producing butyrate, a short-chain fatty acid (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) (SCFA) with anti-inflammatory properties, and in bifidobacteria, which improve the intestinal absorption of calcium, essential for good bone density.

With regard to vaginal microbiota, women suffering from osteoporosis had, compared to the others, fewer lactobacteria, known to attenuate the inflammatory response and its harmful effects, and more streptococci which, to the contrary, promote it.

Toward targeted therapies to better prevent osteoporosis

For the researchers, these compositional changes are fundamental. They could one day be used to develop targeted therapies or serve as biomarkers to better prevent osteoporosis.

Recognized by the World Health Organization, fibromyalgia is characterized by generalized chronic pain, fatigue and sleep disorders. This pathology, which mainly affects women, is often difficult to manage due to a lack of diagnosis or appropriate treatment. A recent cross-sectional study might nevertheless give some hope: it looked at the role of the gut microbiota of fibromyalgia patients, and more specifically at certain bacteria producing secondary bile acids (SBAs).

A dysbiotic gut microbiota

The researchers thus closely examined the gut microbiota (stool samples) and circulating SBAs (blood samples) of 42 Canadian women suffering from fibromyalgia and 42 controls. They observed alterations in the relative abundance of several bacterial species involved in SBA metabolism in these patients: reduced presence of Bacteroides uniformis and B. thetaiotaomicron, known to synthesize an SBA called α-muricholic acid; depletion also of Prevotella copri, a bacterium that affects SBA synthesis and the expression of FXR, a hepatic nociceptor; increased abundance of Escherichia bolteae and Clostridium scindens capable of affecting the metabolism of other SBAs.

SBA alterations

This gut dysbiosis was accompanied by significant alterations in the serum SBA concentration, in particular α-muricholic acid, with levels on average 5 times lower in fibromyalgia patients. Furthermore, this depletion was correlated with pain intensity and fatigue. Thus the decrease in serum SBA levels, and in particular that of α-muricholic acid, could disrupt the normal pain inhibition mechanisms. The authors suggest a mode of action: the decrease in circulating levels of α-muricholic acid (inhibitor of the FXR receptor) and the possible increase in excitatory SBAs could lead to the activation of the FXR receptor, leading to hypersensitivity to pain.

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An objectified diagnosis in the pipeline?

A direct consequence of these observations is the possibility of detecting people with fibromyalgia on the sole basis of the concentration of these serum SBAs. This is a major step forward since diagnosis is currently based solely on subjective measurements. The model developed by the authors shows an accuracy of 91.7%, with a specificity of 90.5% and a sensitivity of 92.9%. Enough to fuel the hope of a future diagnostic tool.

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A recent article may put an end to misdiagnosis for thousands of women suffering from fibromyalgia, a disease characterized by chronic diffuse pain combined with intense fatigue and various issues, including sleep and mood disorders. There are no “markers” for making a diagnosis, such as a lesion in the body (unlike a fracture of the tibia, confirmed via a simple X-ray) or a laboratory parameter (unlike blood sugar levels, which indicate diabetes). This directly affects the quality of life of fibromyalgia patients.

Fibromyalgia: focus on 5 bacteria

New research may mark a turning point. Starting point: studying the differences between the gut microbiota compositions of 42 fibromyalgia patients and 42 other healthy women. Result: of the 16 various bacterial families present in the women with fibromyalgia, three were low while two others seemed quite high. Now, these 5 bacterial species have one thing in common: they transform molecules called primary bile acids (sidenote: Bile acids Bile acids facilitate digestion and absorption of lipids in the intestine. They also exercise hormonal functions and are involved in various metabolic processes. The gut microbiota will modify the bile acids. In return the various bile acids will have an impact on its composition. Staels B, Fonseca VA. Bile acids and metabolic regulation: mechanisms and clinical responses to bile acid sequestration. Diabetes Care. 2009;32 Suppl 2(Suppl 2):S237-S245.  Li R, Andreu-Sánchez S, Kuipers F, Fu J. Gut microbiome and bile acids in obesity-related diseases. Best Pract Res Clin Endocrinol Metab. 2021;35(3):101493.  ) into secondary bile acids (SBA).

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Furthermore, the authors observed differences in the concentrations of certain SBAs in the blood of patients suffering from fibromyalgia – e.g., α-muricholic acid levels were on average 5 times lower in women with this condition! In addition, the lower the α-muricholic acid levels, the greater the pain, fatigue and symptom severity scores. In short, there is a link between an intestinal imbalance and the blood levels of a specific bile acid, which are in turn associated with symptom severity in patients with fibromyalgia.

So can we expect a diagnostic test in the near future?

As a direct consequence of these observations, it may be possible to simply measure the concentration of these small acids, by means of a blood test, to accurately detect people suffering from fibromyalgia. This would enable us to objectify diagnosis of this disease. The model developed by the authors seems promising, showing accuracy of 91.7%. This is enough to raise hopes of a reliable diagnosis becoming available in the future, putting an end to the ordeal for thousands of women.

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Atopic dermatitis (AD) is a complex and multifactorial inflammatory skin disease in which genetics (abnormalities affecting the gene coding for filaggrin, a protein involved in the skin barrier), the immune system, and microbes play a role. For example, the skin of AD patients generally has an increased abundance of Staphylococcus aureus. But what about fungal communities? A recent study¹ has shed some light on this little-known area.

Less Malassezia in severe atopic dermatitis cases

Skin swabs were taken from 16 AD patients (9 cases of mild-to-moderate AD, 7 cases of severe AD) and 16 healthy individuals at four skin sites (antecubital crease, dorsal neck, glabella, and vertex). To observe the course of the disease, the AD patients were sampled at three time points (weeks 0, 2, and 4) and the controls at two time points (weeks 0 and 4).

An analysis of the 320 swabs showed that the Malassezia fungus (particularly the species M. restricta and M. globosa) predominated in all subjects, whether healthy or ill. However, in patients suffering from severe AD, this dominance was reduced in favor of fungi such as Candida or Debaryomyces, resulting in greater fungal diversity.

As for bacteria, AD was characterized by lower levels of Cutibacterium and a greater relative abundance of Staphylococcus, particularly S. aureus and S. epidermidis. A higher presence of S. aureus may favor the proliferation of Candida, a synergistic activity between the two microorganisms having previously been shown. 

Lastly, no changes in the fungal or bacterial microbiota were observed over the four weeks, regardless of the skin site.

Linked to AD severity

The study also showed a link between skin dysbiosis and the severity of AD: the bacterial and fungal communities of patients with severe AD differed significantly from those of controls and patients with mild-to-moderate forms of the disease. The skin communities of the latter two groups (mild-to-moderate AD and controls) were similar overall, with some distinctions in the bacterial communities (more staphylococci and less cutibacteria in mild-to-moderate AD versus no AD). Thus, a pronounced dysbiosis of the microbiota is characteristic of severe forms of AD, but not of less severe forms.

Dry and itchy skin, red plaques (especially in the folds) that appear in flares: atopic dermatitis (AD) is an inflammatory skin disease that affects nearly one in five infants. Although AD tends to improve with age, it is estimated that one in ten adults suffers from the disease in developed countries.

Why my child and why me? Many factors are involved, with both heredity (children of adults affected by AD are more likely to suffer from the disease) and the immune system playing important roles. Another key factor is the skin microbiota, the complex community 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. ) (bacteria, fungi, parasites, and viruses) residing on our skin.

Malassezia depleted

In AD patients, some bacteria, such as Staphylococcus aureus, tend to be overrepresented, while others, such as Cutibacterium, are depleted. And what about microscopic fungi? There was no clear answer to this question until a recent study showed that the skin’s fungal flora differs in cases of severe dermatitis. Thus, while the Malassezia fungus predominates on healthy skin, it loses its prime position in AD patients. In its place, other fungi such as Candida or Debaryomyces make themselves at home. In other words, in cases of severe dermatitis, where Malassezia no longer dominates the skin fungi, there is greater fungal diversity.

Moreover, changes in the bacterial and fungal populations may be linked. For example, an increased abundance of S. aureus may favor the proliferation of Candida, as these two microorganisms have been shown to exhibit a synergistic activity.

Linked to AD severity

This skin microbiota imbalance (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.   ) appears to be linked to the severity of AD. With a few exceptions, the skin microbiota of patients suffering from non-severe AD is similar overall to that of individuals with healthy skin. On the other hand, the researchers found a strong divide between patients suffering from severe AD and those with healthy skin or mild-to-moderate AD. One important reason for this is lower levels of Malassezia.

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On the occasion of the World AMR Awareness Week organized each year by the WHO, the Biocodex Microbiota Institute makes a full review.

Antibiotics: how do they impact our microbiota?

Antibiotics do not always distinguish between good and bad bacteria. They destroy not only pathogenic bacteria, but also beneficial bacteria in the gut microbiota. These disruptions reduce bacterial diversity, which weakens our natural defenses and promotes certain imbalances.

Discover our articles to better understand how antibiotics influence our microbiota:

Antibiotics: what are the long-term effects on our health?

Early or repeated exposure to antibiotics can have a lasting effect on the composition of the microbiota and increase the risk of immune, digestive, or allergic disorders. Its effects do not always stop at the end of treatment. Their influence on the microbiota can leave significant traces on our health. These disturbances remind us of the importance of sensible use to protect our long-term health and limit imbalances in the microbiota.

Discover how antibiotics can influence our health from an early age:

Antibiotics: why is antibiotic-associated diarrhea under the spotlight?

Post-antibiotic diarrhea is a common consequence of intestinal microbiota disrupted by drug treatment. By altering the protective flora, certain antibiotics pave the way for imbalances or the proliferation of opportunistic bacteria. Restoring this balance is essential for maintaining digestive health.

Explore our articles to understand the link between antibiotics, microbiota, and diarrhea:

Antibiotics: what is "antibiotic resistance"?

Antibiotic resistance occurs when certain bacteria are no longer killed by drugs. Antibiotics destroy the microbes responsible for infections, but also other beneficial bacteria. Those that resist can then multiply and pass on their resistance to others, making infections more difficult to treat.

Discover our articles to better understand antibiotic resistance:

Antibiotics: can we protect our microbiota?

In response to the disruption caused by antibiotics, there are solutions available to support the microbiota: reduced exposure to antibiotic treatments, a varied diet, and the use of prebiotics and probiotics. These allies help restore bacterial balance and reduce the effects of treatment-induced disruption, leading to better overall health.

Discover how to preserve the balance of your microbiota when taking antibiotics:

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Today, we speak of the "intestine-liver axis". Originating from the same germ layer, the liver and intestines are indeed connected at the anatomical and functional level, in particular through biliary secretion and the hepatic portal system. Furthermore, there is mounting evidence of an association between hepatitis B and alterations in the composition of the gut microbiota. However, no study had explored these changes as the disease progresses from chronic to cirrhosis to hepatocellular carcinoma.

A team therefore conducted a systematic meta-analysis of 16S sequencing results (from public databases) from fecal samples collected from HBV-infected patients at all stages of liver disease. Signatures of eventually identified microbiota were then validated in independent cohorts (23 chronic hepatitis B patients, 20 cirrhotic patients, 22 patients with hepatocellular carcinoma and 15 controls).

^{Sources (sidenote: Hepatitis B WHO (2017) )}

Microbiota signatures as a function of progression 

The researchers identified 13 bacterial genera that differed at each stage of liver disease, consistent between public data sets and validation cohorts. While the genera Monoglobus and Colidextribacter were more present in healthy controls, species belonging to the family Lachnospiraceae were specifically increased in chronic hepatitis B while Bilophia were reduced. The genera Prevotella and Oscillibacter were decreased in cirrhosis, Coprococcus and Faecalibacterium in hepatocellular carcinoma. According to the authors, these results indicate a decrease in key taxa of the gut microbiota at each stage of the disease, and an increasingly pronounced dysbiosis as the disease worsens. 

Their analyses corroborate the results of previous studies: Monoglobus, Colidextribacter and Bilophila were associated with protection against inflammation and/or liver damage and Prevotella and Oscillibacter were found to be decreased in severe alcoholic hepatitis. In addition, Coprococcus and Faecalibacterium produce butyrate, the depletion of which is thought to alter intestinal permeability and increase translocation of cancer-promoting bacteria.

New non-invasive biomarkers?

The use of these 13 bacterial genera reveals a diagnostic power to distinguish all stages of the disease, with varying degrees of accuracy (confirmed on data from databases and independent cohorts). These microbial signatures could serve as biomarkers for non-invasive monitoring of hepatitis B, according to the researchers, but also contribute to the development of therapies based on the gut microbiota.