Dysbiosis in the spotlight: the gut microbiota 

Our gut microbiota is the human body's main microbiota.² It contains at least 1000 different species³ of microorganisms, including bacteria, fungi and viruses. The Firmicutes group (which includes the well-known "good bacteria", lactobacilli) and the Bacteroidetes group together account for 70–90% of the bacterial community in our gut.^2,4 Our microbiota also contains Actinobacteria, which include bifidobacteria, known for their beneficial effects. Other microorganisms in our microbiota can make us ill. These are referred to as "potential pathogens (sidenote: Pathogen A pathogen is a microorganism that causes, or may cause, disease. Pirofski LA, Casadevall A. Q and A: What is a pathogen? A question that begs the point. BMC Biol. 2012 Jan 31;10:6. ) ", but they are in the minority.² Dysbiosis involves one or more of the following phenomena:

• A significant change in the relative proportions of the major bacterial families, in particular a loss of lactobacilli and bifidobacteria;⁵
• A reduction in or total loss of the useful microorganisms that usually live in our microbiota (known as "commensal" microorganisms);¹
• A decrease in the diversity of the microorganisms found in the microbiota, meaning there are fewer different species;⁵
• The growth of potentially pathogenic microorganisms within the microbiota.^1,5

As a result, our microbiota is weakened and the "bad" bacteria take over from the "good" bacteria.² It becomes harder for the microbiota to protect the body from attack and to carry out its essential roles relating to our health and well-being.^1,6

What does a dysbiosis look like?

While dysbiosis itself is not considered a disease, it has been linked to various health problems and may contribute to the development or exacerbation of certain medical conditions.

Our own unique microbiota imbalance

However, "dysbiosis" is not a universal term that can be applied to anyone in any circumstance! ¹ In fact, the composition of our microbiota is particular to each person, and is influenced by our genes and by the microorganisms that colonised our body during our first years of life ("microorganisms" are defined as "living organisms that are too small to be visible with the naked eye. This includes bacteria, viruses, fungi, archaea, protozoa and so on, collectively known as 'microbes (sidenote: https://microbiologysociety.org/why-microbiology-matters/what-is-microbiology.html ) '). The microbiota varies so considerably between individuals that it could well be as unique to each of us as our fingerprints.⁷ What's more, it can change depending on our age, health, stress levels and diet, as well as where we live and any medicines we are taking.⁸ This means that each of us can experience our own specific dysbiosis when our microbiota becomes imbalanced and no longer functions correctly within our body.¹

What causes dysbiosis?

As its definition suggests, dysbiosis occurs under the influence of numerous very different and often interrelated factors.⁵ Among these are the following:

Factors linked to the individual themselves, such as:

• Genetics;¹ 
• Age;¹¹
• Certain diseases and injuries;¹ 

Factors linked to the individual's environment, such as:

• Taking medicines: antibiotics, anti-inflammatories, etc.;^2,5 
• Infections;¹²
• Lifestyle: unbalanced diet or changes in diet, stress, smoking, poor hygiene, etc.;^1,5,8
• Pollution.⁸

What can cause a dysbiosis ?

Dysbiosis and diseases specific to each microbiota

Dysbiosis: a cause or a consequence of illness?

Numerous studies comparing the microbiotas of ill and healthy people have shown that dysbiosis is associated with a range of chronic conditions, including intestinal diseases such as irritable bowel syndrome and Crohn's disease, as well as obesity, allergies, asthma and certain cancers¹. But is it the dysbiosis that causes the disease or the disease that causes the dysbiosis? According to scientists, the answer is still unclear, but numerous studies are currently under way to try and work it out.

In 2019, researchers launched Homo symbiosus, an extensive research project that aims to get to the bottom of this issue and give us a better understanding of why and how so many chronic diseases are associated with gut dysbiosis. The researchers' hypothesis is that "the phenomena of gut dysbiosis, microbial growth, inflammation and weakening of the intestinal wall" are mutually sustaining¹⁰.

Dysbiosis of the gut microbiota is associated with a variety of diseases, including gastrointestinal, metabolic²², allergic23 and even mental²⁴ conditions. But the human body is also home to specific microbial ecosystems located in the skin²⁵, urinary tract²⁶, vagina²⁷, mouth²⁸ and lungs²⁹, all of which can also become unbalanced and be associated with specific diseases.

How can we rebalance the microbiota?

Normally, after an episode of dysbiosis, the microbiota is able to naturally restore its initial balance (although it will never have exactly the same composition as before): it is said to be "resilient" ³⁰. But sometimes, this "re-biosis", or return to microbial balance, can take time: even in a healthy adult, for example, it can take six months after taking antibiotics ³¹. Eventually, dysbiosis can lead to a prolonged state of imbalance that is self-sustaining over the long term, with the microbiota never fully returning to normal, which can be harmful to health ¹ .

What should we do when dysbiosis strikes? There are several potential solutions to help us rebalance the microbiota and improve our health.

BMI-21.48

1. Antibiotics save lives 

Since the discovery of penicillin in 1928, the widespread use of antibiotics has saved millions of lives. The main weapon in the fight against bacterial infections, antibiotics, alongside vaccinations, have added nearly twenty years to life expectancy.¹  

2. Antibiotics destroy species responsible for infections, but also eliminate good bacteria

Gut, vagina, lungs, skin... many parts of the body play host to microorganisms (bacteria, fungi, viruses). Such microbial communities are known as microbiota.² Antibiotics eradicate pathogenic germs responsible for infection but can also destroy certain beneficial bacteria in our microbiota, leading to imbalances (dysbiosis (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.   ) ³) of varying degrees within these ecosystems. This concerns all of the body’s microbiota, including: the gut, skin,⁴ lung,⁵ ENT,⁶ urinary,⁷ and vaginal microbiota.⁸ 

3. Antibiotics can have side effects 

By inducing a dysbiosis, antibiotics can have harmful effects on health. The main short-term complication is the alteration of bowel movements experienced by some patients. This most often results in diarrhea, with the gut microbiota less able to perform its protective functions. Antibiotic-associated diarrhea is usually mild to moderate⁹ in intensity, but its incidence varies according to age, type of antibiotic, context, etc. It may affect up to 35%^9,10,11 of patients and 80% of children.⁹ In 10%-20% of cases, the diarrhea results from an infection by Clostridioides difficile (C. difficile),¹¹ a bacterium that colonizes the gut microbiota and becomes pathogenic due to certain factors (e.g. antibiotic use). The clinical consequences vary, ranging from moderate diarrhea to much more serious symptoms, or even death.¹¹ 

4. Antibiotics are thought to be responsible for longer-term effects

Diarrhea is not the only symptom of antibiotic-associated dysbiosis. When it occurs early in life, the condition is thought to be responsible for longer-term effects. The perinatal period, characterized by the development of the gut microbiota and the maturation of the immune system, is a particularly sensitive period.¹² Antibiotic-associated dysbiosis during this phase seems to be a risk factor in the development of certain chronic diseases (obesity, diabetes mellitus, asthma, inflammatory bowel disease).¹³ 

 5. Inappropriate use of antibiotics is responsible for antibiotic resistance 

Antibiotic resistance happens when an antibiotic treatment is no longer effective against a bacterial infection.¹ The cause? Antibiotics are only effective against bacteria and have no effect on viruses (e.g. the flu).¹⁴ The inappropriate (e.g. with viral infections) or excessive use of antibiotics – in humans or animals – accelerates antibiotic resistance. Antibiotic resistance leads to longer hospitalizations, higher health care costs and more deaths. For this reason, the issue has become a major public health concern worldwide.¹

6. World Antimicrobial Awareness Week 

Each year, from November 18 to 24, the WHO organizes World AMR Awareness Week, which aims to increase awareness of global antimicrobial (sidenote: Antimicrobial Class of drugs that includes antibiotics (active against bacteria), antiviral agents (active against virus), antiparasitic agents (active against parasites), and antifungal agents (active against fungi). WHO Antimicrobial Resistance; Oct 2020 ) resistance and to encourage best practices among the general public, health workers and policymakers to avoid the further emergence and spread of drug-resistant infections. As an expert on microbiota, the Biocodex Microbiota Institute takes part in this initiative.

Infographics to share with your patients

1. Antibiotics save lives 

Since the discovery of penicillin in 1928, the widespread use of antibiotics has saved millions of lives. The main weapon in the fight against bacterial infections, antibiotics, alongside vaccinations, have added nearly twenty years to life expectancy.¹  

2. Antibiotics destroy species responsible for infections, but also eliminate good bacteria

Gut, vagina, lungs, skin... many parts of the body play host to 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, viruses). Such microbial communities are known as microbiota.² Antibiotics eradicate pathogenic germs responsible for infection but can also destroy certain beneficial bacteria in our microbiota, leading to imbalances (dysbiosis (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.   ) )³ of varying degrees within these ecosystems.

This concerns all of the body’s microbiota, including:

• the gut microbiota,
• the skin microbiota,⁴ 
• the lung microbiota,⁵ 
• the ENT microbiota,⁶ 
• the urinary microbiota,⁷ 
• and the vaginal microbiota.⁸ 

3. Antibiotics can have side effects 

By inducing a dysbiosis, antibiotics can have harmful effects on health. The main short-term complication is the alteration of bowel movements experienced by some patients. This most often results in diarrhea, with the gut microbiota less able to perform its protective functions. Antibiotic-associated diarrhea is usually mild to moderate⁹ in intensity, but its incidence varies according to age, type of antibiotic, context, etc. It may affect up to 35%^9,10,11 of patients and 80% of children.⁹ In 10%-20% of cases, the diarrhea results from an infection by Clostridioides difficile (C. difficile),¹¹ a bacterium that colonizes the gut microbiota and becomes pathogenic due to certain factors (e.g. antibiotic use). The clinical consequences vary, ranging from moderate diarrhea to much more serious symptoms, or even death.¹¹ 

 4. Antibiotics are thought to be responsible for longer-term effects

Diarrhea is not the only symptom of antibiotic-associated dysbiosis. When it occurs early in life, the condition is thought to be responsible for longer-term effects. The perinatal period, characterized by the development of the gut microbiota and the maturation of the immune system, is a particularly sensitive period.¹² Antibiotic-associated dysbiosis during this phase seems to be a risk factor in the development of certain chronic diseases (obesity, diabetes mellitus, asthma, inflammatory bowel disease).¹³ 

 5. Inappropriate use of antibiotics is responsible for antibiotic resistance 

Antibiotic resistance happens when an antibiotic treatment is no longer effective against a bacterial infection.¹ The cause? Antibiotics are only effective against bacteria and have no effect on viruses (e.g. the flu).¹⁴ The inappropriate (e.g. with viral infections) or excessive use of antibiotics – in humans or animals – accelerates antibiotic resistance. Antibiotic resistance leads to longer hospitalizations, higher health care costs and more deaths. For this reason, the issue has become a major public health concern worldwide.¹

6. World AMR Awareness Week

Each year, from November 18 to 24, the WHO organizes World AMR Awareness Week, which aims to increase awareness of global antimicrobial (sidenote: Antimicrobial Class of drugs that includes antibiotics (active against bacteria), antiviral agents (active against virus), antiparasitic agents (active against parasites), and antifungal agents (active against fungi). WHO Antimicrobial Resistance; Oct 2020 ) resistance and to encourage best practices among the general public, health workers and policymakers to avoid the further emergence and spread of drug-resistant infections. As an expert on microbiota, the Biocodex Microbiota Institute takes part in this initiative.

On the one hand, they are an extraordinary scientific discovery that saves millions of lives. On the other, their excessive and sometimes inappropriate use can lead to the emergence of multiple forms of resistance in microorganisms (including bacteria, viruses, parasites and fungi). As a result, although they were designed to heal, antimicrobials are becoming less and less effective and, ultimately, if no action is taken, there is a risk that they will no longer be able to protect us from infections.

Antimicrobial resistance would become responsible for almost 700,000 annual deaths worldwide². If nothing changes, infectious diseases could become one of the leading causes of mortality worldwide by 2050, causing up to 10 million deaths².

As a major centre of expertise on the microbiota, the Microbiota Institute has been an active partner for the event since 2020. Throughout November, the Institute will be sharing articles and news, as well as expert videos and downloads on key topics, to enhance your knowledge and help you understand the mid- and long-term effects of antibiotics on the human microbiota. To cite just one example, despite their well-known efficacy against bacteria (and lack of efficacy against viral infection³), they often lead to dysbiosis. This is associated with several well-known problems, such as antibiotic-associated diarrhea.

But there's more! Taking antibiotics is also suspected to increase the risk of multiple chronic diseases⁴ (allergies, asthma, obesity, chronic inflammatory bowel disease, etc.), particularly if they are prescribed in early childhood. So can we do anything about it? Yes! By encouraging good prescription practices to ensure that antibiotics are used properly! But also by educating patients on the risks of dysbiosis associated with excessive and inappropriate use of antibiotics. We are all responsible and we all have a role to play in reducing antimicrobial resistance!

On the one hand, they are an extraordinary scientific discovery that saves millions of lives. On the other, their excessive and sometimes inappropriate use can lead to the emergence of multiple forms of resistance in microorganisms (including bacteria, viruses, parasites and fungi). As a result, although they were designed to heal, antimicrobials are becoming less and less effective and, ultimately, if no action is taken, there is a risk that they will no longer be able to protect us from infections.

Antimicrobial resistance would become responsible for almost 700,000 annual deaths worldwide². If nothing changes, infectious diseases could become one of the leading causes of mortality worldwide by 2050, causing up to 10 million deaths².

As a major centre of expertise on the microbiota, the Microbiota Institute has been an active partner for the event since 2020. Throughout November, the Institute will be sharing articles and news, as well as expert videos, to help you understand the mid- and long-term effects of antibiotics on the human microbiota. To cite just one example, despite their well-known efficacy against bacteria (and lack of efficacy against viral infection³), antibiotics disrupt the balance of our gut microbiota. This imbalance, more commonly known as dysbiosis (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.   ) , is associated with several well-known problems, such as antibiotic-associated diarrhea. But there's more! Taking antibiotics is also suspected to increase the risk of multiple chronic diseases (allergies, asthma, obesity, chronic inflammatory bowel disease, etc.), particularly if they are prescribed in early childhood.

So can we do anything about it? Yes! Firstly, by ensuring that antibiotics are used sensibly and appropriately. Do not take these medications without a prescription from a healthcare professional. Stick to the specified dose, administration frequency and duration of treatment and do not share your antibiotics with anyone else⁴. And remember, as the French health slogan states:

Antibiotics: handle with care© !

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A single purpose: explore the connection between prostate cancer and gut microbiota in a group of Japanese men. A single methodology: the profiles of the gut microbiota in men with and without high grade prostate cancer were compared. A single objective: determine whether the composition of the gut microbiota can be used as a new, non-invasive marker of high grade prostate cancer.

In search of a new marker...

The cancer is diagnosed via rectal examination and a number of clinical examinations that assess the severity of the cancer and the risk of progression, and help to determine the treatment options (sidenote: Mohler JL, Antonarakis ES, Armstrong AJ, et al. Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2019;17(5):479-505. ) . The vital screening and follow-up examination for prostate cancer is the prostate specific antigen (PSA) assay, although it does not accurately identify the grade of the cancer. The grade is assessed on a scale from 1 to 5, following examination of tissue samples from the prostate. At grade 1, patients’ prognosis is generally favourable, so it is recommended that no treatment be given, in order to avoid overtreatment which can often have an adverse impact.  By contrast, patients with grade 2 prostate cancer and above require prompt, appropriate treatment. A new method for grading prostate cancers needs to be developed as a matter of priority to supplement the serum PSA test and avoid invasive examination. 

...In the intestinal microbiota

In a previous study, the authors showed that in mice, obesity, a fatty diet and even certain molecules produced by the gut microbiota tend to promote the proliferation of prostate cancer cells.  These results suggest that the gut microbiota could be used as a biomarker for determining how the cancer will progress. When they analysed the intestinal microbiota of patients who had undergone a prostate biopsy, the researchers found that three groups of bacteria were more abundant in patients with a high grade prostate cancer. To improve the accuracy of the diagnosis, the authors used a mathematical model and identified a further 18 types of bacteria to create the Fecal Microbiome Prostate Index, or FMPI. This FMPI index can be used to identify patients with a high grade prostate cancer with greater accuracy than conventional PSA assay. 
While very encouraging, this study remains localised and the scope of the research is limited, with only men who were Japanese citizens being included. It now needs to be conducted in more patients, with different profiles, thereby confirming what are promising results. 
 

^Source:

^{Matsushita M, Fujita K, Motooka D, et al. The gut microbiota associated with high-Gleason prostate cancer. Cancer Sci. 2021.}

Osteoarthritis, a condition that makes joints seize up and become misshapen, blights the life of more than 3% of the world’s population, especially seniors. 10% of men and 18% of women over 60 are suffering from this painful and debilitating joint disease. It has multiple causes: genetics, gender, age, obesity, sedentary lifestyle… and maybe even the gut microbiota. We already know that our gut bacteria are involved in several inflammatory diseases, and they might also play a role in osteoarthritis-related inflammation.

How an unbalanced gut microbiota correlates with osteoarthritis

To learn more about the relationship between gut microbiota and osteoarthritis in elderly women, researchers compared the stool bacterial composition of 57 women aged 65 on average suffering from osteoarthritis and that of 57 healthy volunteers of the same age (control). The gut microbiota of patients with osteoarthritis was generally less abundant and less diversified. Some beneficial bacteria are less prevalent, such as Bifidobacterium longum which regulates the immune system, or Faecalibacterium prausnitzii, an anti-inflammatory bacterium known for its health benefits in humans. On the contrary, the content of some pathogenic bacteria such as Clostridium ramosum is increased. In addition, some functions of the gut microbiota seem to be disrupted in case of osteoarthritis, thus suggesting a reduced ability to benefit from food.

When could the gut microbiota help with diagnosis, and even treatment?

Since the gut microbiota of patients with osteoarthritis is different from that of controls–thus suggesting that the gut microbiota could be a risk factor–the research team tried to develop a predictive tool for the disease based on the presence of 9 bacteria in the patients’ stools. Their predictive model was proven reliable in the elderly women from the study but has not yet been verified in other patient groups. The presence of these bacteria could well prove to be useful in establishing a diagnosis. These microorganisms could also open up new treatment options for osteoarthritis based on prebiotics or probiotics. Ultimately this could lead to better pain relief and improved quality of life for osteoarthritis patients.

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Coconut oil for the scalp microbiota!

^{Saxena R, Mittal P, Clavaud C. et al. Longitudinal study of the scalp microbiome suggests coconut oil to enrich healthy scalp commensals. Sci Rep 2021; 11: 7220.}

A recent study has shown that coconut oil can help maintain a healthy scalp by improving the scalp microbiota. The researchers compared the impact of coconut oil and a neutral shampoo on the scalp bacterial and fungal microbiota of 140 women with and without dandruff. The scalps of the women with dandruff had a much higher abundance of uncharacterized Malassezia species, fungus known to accelerate the development of dandruff and inflammation. Conversely, the fungus species M. globosa, was found in abundance on the scalps of the women with no dandruff or itching. Treatment with coconut oil brought the ratio of M. globosa to other groups of Malassezia in line with that of healthy scalps. Although no significant differences were observed between the bacterial microbiota of the healthy group and that of the dandruff group, both groups saw an increase in bacteria involved in the metabolism of biotin following coconut oil treatment. Biotin, a B vitamin that is essential for the maintenance of healthy skin and a healthy scalp, is also known to reduce inflammation. Further studies are required to understand the underlying mechanisms, but for the researchers, the positive effect of coconut oil on the composition and function of the scalp microbiota is the first step towards the longer-term restoration of scalp health.

Using recombinant endolysins to treat bacterial vaginosis

^{Landlinger C, Tisakova L, Oberbauer V. Engineered phage endolysin eliminates gardnerella biofilm without damaging beneficial bacteria in bacterial vaginosis ex vivo. Pathogens 2021; 10: 54.}

A study has shown that by using recombinant endolysins of the type 1,4-beta- N-acetylmuramidase encoded on Gardnerella prophages it is possible to eliminate the bacterial biofilm responsible for bacterial vaginosis without damaging the beneficial bacteria of the vaginal microbiota. To this end, the authors generated several engineered endolysins, bacteriophage enzymes that lyse the bacterial wall, via domain shuffling. They compared their bactericidal activity on Gardnerella strains to that of wild-type endolysins. The bactericidal activity of the recombinant endolysins was 10 times that of any wild-type enzyme. When tested against a panel of 20 Gardnerella strains from 4 species (G. vaginalis, G. leopoldii, G. piotii and G. swidsinski), the most active endolysin, called PM-477, showed superior efficacy compared to the antibiotics tested (metronidazole, tinidazole, clindamycin). Furthermore, PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. According to the authors, PM-477 is highly selective for Gardnerella and kills strains of each of the four main species without affecting beneficial lactobacilli or other species typical of the vaginal microbiota. The effect of PM-477 was confirmed by microscopy in mixed cultures of Gardnerella and lactobacilli. To go further and analyze the efficacy of PM-477 in a physiological environment closely resembling the in vivo situation, the researchers treated vaginal swabs from 15 bacterial vaginosis patients and analyzed them by fluorescence in situ hybridization (FISH). They showed that in 13 of the 15 cases, PM-477 eradicated the Gardnerella bacterium and physically dissolved the biofilms without affecting the vaginal microbiota. According to the authors, endolysins are a promising therapeutic alternative to antibiotics for the treatment of bacterial vaginosis.