The oropharyngeal microbiota (OM) normally comprises a wide variety of bacteria that help maintain a balanced local environment. Some illnesses and drugs such as proton pump inhibitors (PPIs) can disturb this balance, thereby allowing opportunistic pathogens to colonize the oropharyngeal tract. Microaspiration of these pathogens during hospitalization can lead to colonization of the lower respiratory tract, increasing the risk of nosocomial pneumonia. Early detection of oropharyngeal disturbance may be a means to reduce incidence. A team of researchers studying the occurrence of the disturbance during hospitalization has identified patient characteristics associated with the disorder.

Oropharyngeal disturbance increases with length of hospital stay

Oropharyngeal samples were collected from 134 hospital patients within 24 hours of admission, on day 3 of hospitalization, and then every four days for the remainder of their stay. The samples were analyzed by conventional bacterial culture and MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry, with the pathogens then classified into three categories: respiratory tract pathogens, gut microbiota species and yeasts. In 89% of the patients, the swab collected at admission showed a balanced OM. The authors found that a significant proportion of patients developed an OM disturbance during their stay, and that the number of patients with the disorder increased with the length of stay.

Antibiotics and PPIs responsible for disturbance

The prescription of antibiotics during hospitalization appears to be associated with this imbalance. Similarly, PPI and antibiotic use prior to hospitalization are predictive of an OM disturbance consisting of colonization by bacterial species from the gut microbiota. The study found that the risk of nosocomial pneumonia increased in patients treated with PPIs or antibiotics prior to hospitalization. Conversely, patients admitted to hospital on a short-term basis had a lower risk of oropharyngeal colonization by gut pathogens. These results underline the need for vigilance in the management of patients with risk factors associated with OM disturbance. Patients admitted to hospital with ongoing antibiotic or PPI treatment may well benefit from more aggressive physiotherapy aimed at maximizing lung aeration and minimizing aspiration. In this way, early detection of an OM disturbance may reduce the incidence of nosocomial pneumonia.

While Covid-19 usually produces respiratory symptoms, a significant proportion of patients suffer from gastrointestinal disorders such as diarrhea, vomiting or abdominal pain. In a review of 35 studies involving 6,686 Covid-19 patients, 29 of the studies showed a 4% prevalence of gastrointestinal symptoms and a 19% prevalence of liver function abnormalities. These symptoms were more severe with increased viral load. In addition, approximately 10% of patients had gastrointestinal symptoms only, and no respiratory symptoms.

A deregulation of ACE2 in the gut

To link bowel disorders to Covid-19, the researchers investigated the role of ACE2 (receptor for the SARS CoV-2 Spike protein (sidenote: The Spike protein, or S protein, is the key that allows SARS-CoV-2 to enter human cells ) ) in gut inflammation. Highly expressed in the gut, its function is to control the absorption of dietary amino acids such as tryptophan, which plays an important role in immunity. Indeed, several preclinical studies suggest that gut ACE2 is an essential regulator of gut inflammation. In an ACE2 knockout (sidenote: ACE2 knockout mouse An ACE2 knockout mouse is a mouse model in which the ACE2 gene is absent )  mouse model, the absence of the ACE2 gene leads to more severe colitis (sidenote: A sodium dextran sulphate (DSS)-induced colitis model ) . In another model (animals treated with an antihypertensive drug (sidenote: Angiotensin receptor blocker (ARB) ) ) with stress-induced inflammation, increased ACE2 expression correlated with reduced inflammation. Therefore, an ACE2 deficiency increases gut’s susceptibility to inflammation.

A lasting gut dysbiosis?

Furthermore, the digestive tract takes longer to excrete SARS-CoV-2 than the respiratory tract. SARS-CoV-2 RNA persists in the stool in over half of patients even after a negative nasopharyngeal swab test and up to 33 days after symptomatic healing of a lung lesion. A study on 15 patients also showed persistence of gut dysbiosis well beyond infection, with a loss of beneficial species in most patients. Exposure to SARS-CoV-2 may therefore be associated with long-lasting harmful effects on the gut microbiota.

According to the authors, by down-regulating gut ACE2, SARS-CoV-2 may modify the gut microbiota and increase systemic inflammation, which may explain the multiple organ failure observed in Covid-19.

As the sixth leading cause of cancer death, esophageal cancer remains highly lethal, with five-year survival rates of 15%-20%. Esophageal squamous cell cancer (ESCC) is the most common subtype of the disease. Current treatments include neoadjuvant chemotherapy (sidenote: Neoadjuvant chemotherapy To reduce tumor size prior to surgery )  (NAC) followed by esophageal resection. Although patients who respond favorably to NAC have a better chance of survival, most tumors develop NAC resistance. Understanding the mechanisms behind NAC resistance is therefore key to improving treatment response and, accordingly, patient survival.

What role does Fusobacterium nucleatum play in tumors?

The composition of the gut microbiota has already been shown to influence responses to certain cancer treatments such as immunotherapy and chemotherapy. In addition, intratumoral Fusobacterium nucleatum levels have recently been shown to be associated with reduced survival and/or increased recurrence rates in colorectal cancer and in ESCC. This encouraged researchers to assess, for the first time, the prognostic value of intratumoral F. nucleatum levels in ESCC patients and their ability to predict NAC response. The study was carried out in 551 Japanese subjects from two independent cohorts.

Predictive marker of reduced survival rate...

First finding: tumor tissue has higher levels of F. nucleatum compared to adjacent healthy tissue. In addition, intratumoral F. nucleatum levels are associated with both the stage of tumor progression and a reduction in relapse-free survival (RFS). The link between F. nucleatum and reduced survival is observed even in early-stage patients, suggesting that this bacterial species may promote tumor aggressiveness. Intratumoral F. nucleatum levels may therefore serve as a prognostic biomarker.

... and poor responses to chemotherapy

Lastly, analyses in a subgroup of 101 patients receiving NAC showed that patients with increased levels of F. nucleatum had a lower response to tumor treatment. Although the mechanisms likely to explain the role of F. nucleatum in increased tumor resistance remain speculative (activation of metabolic pathways leading to cell autophagy?; deactivation of chemotherapeutic substances?), the researchers point out a promising therapeutic avenue: improving responses to chemotherapy via an antibiotic therapy targeting F. nucleatum. More work to follow.

The microbial world present in the air, soil and plants is considered critical for our health. Certain theories suggest that low exposure to green spaces and to the microorganisms found in them has contributed to the contemporary rise in obesity, diabetes mellitus, and allergies. Therefore, a better understanding of the interactions between man and nature, and especially between microbiota and environment, seems key to fighting these non-communicable diseases. To this end, a team of scientists evaluated the impact of green spaces on the composition and diversity of the skin and nasal flora of three individuals following visits to urban green spaces in three different countries, Australia, India, and the UK.

Green spaces increase microbial diversity

During their walks, the participants took soil, leaf, and air samples in order to analyze the bacteria in the environment. They also took samples from their nose and skin before and after each exposure to the environment so as to assess the impact of green spaces on their microbiota. The analysis revealed that the skin flora had changed following the walk: it was richer in bacteria, more diverse and closer to that of the soil, evidence that environmental bacteria had colonized the skin. Furthermore, the composition of the nasal microbiota was similar to that of air samples.

Transient changes?

Even more interesting was the overall similarity between the changes in microbial diversity and composition in the three countries visited, even though many factors known to influence the composition of the microbiota, such as pollution, humidity, or diet, differed between these three countries. It is not yet known how long these changes in the flora last, but previous studies suggest that most environmental bacteria transferred to humans disappear after 2 hours, with less common types potentially persisting for up to 24 hours on the skin. Further research is required to establish whether there are any health benefits from these microbial changes, but in the meantime, feel free to roll around in the grass!

As part of World Antimicrobial Awareness Week (18-24 November 2020), the WHO encouraged the general public, health workers and decision-makers to adopt best practices in order to avoid the emergence and spread of antimicrobial resistance. While antibiotics were one of the major therapeutic advances of the 20th century, they can also have an adverse impact on the body’s various microbiota. Although the short-term effects of some classes of antibiotics on the gut microbiota are well known, the long-term effects are not yet fully understood. This study compared the impact of 15 classes of antibiotics on the composition of the gut microbiota up to four years after the last dose.

“Large scale” study

The composition of the gut microbiota of 1413 participants (median age: 62.6 years) who had previously taken antibiotics was analyzed by 16S rRNA sequencing. The time elapsed from the last dose of antibiotics to the day of sampling was categorized as follows: 0-12, 12-24, 24-48 and >48 months. The results were adjusted for certain confounding factors (sex, age, BMI, diabetes mellitus, concomitant medications such as statins, PPIs, corticosteroids, etc.).

Impact of macrolides and lincosamides

The most significant and prolonged impact on the gut microbiota was observed for macrolides and lincosamides: decrease in Shannon ratio that lasted for 4 years after the last administration, and significant change in bacterial community structure (Bray-Curtis diversity ratio). A significant loss of diversity was also observed one year after use of beta-lactams.

Impact of antibiotics with high anti-anaerobic activity

The results also revealed that antibiotics with high anti-anaerobic activity (penicillin/beta-lactamase inhibitor combinations, imidazole derivatives and lincosamides) had a greater and longer-lasting impact on the gut microbiota than other classes: the Firmicutes/Bacteroidetes ratio significantly shifted in favor of Firmicutes up to one year after administration, while this ratio significantly shifted in favor of Bacteroidetes up to two years after taking antibiotics with no anti-anaerobic activity.

Therefore, macrolides and lincosamides are associated with an acute and long-lasting dysbiosis of the gut microbiota. These effects differ in strength and duration depending on the class of antibiotic used. According to the authors, these findings should be considered when prescribing antibiotics.

Cardiovascular disease (CVD) is the world’s number one cause of death. By 2030, CVD-related deaths are expected to peak at 23.6 million. Its diagnosis currently involves a series of time-consuming and costly examinations (clinical tests, ECG, chest X-rays, echocardiogram). An alteration (dysbiosis) of the gut microbiota has been linked to several types of CVD, including hypertension, heart failure and atherosclerosis. So why not use artificial intelligence to design a diagnostic test for CVD based on gut microbiota composition?

CVD “signatures” present in the stool

Machine learning is a branch of artificial intelligence that involves inputting data into a computer so that it can learn how to solve a problem. In healthcare, it has been successfully used to diagnose and predict various diseases, such as cancer, diabetes mellitus and inflammatory bowel disease. To test its usefulness for diagnosing CVD, a team of researchers compared different analytic algorithms and sought to identify characteristic “signatures” for the disease in stool samples obtained from 478 patients with CVD and 473 healthy subjects. They found significant differences between the two groups in the relative intestinal abundance of 39 bacteria.

Strong diagnostic capacity

The researchers identified a specific algorithm which, by targeting 25 bacterial families within the gut microbiota, could discriminate between the two groups with 70% accuracy. This level of accuracy is only slightly below that of the conventional approach, which is able to diagnose 76% of CVD patients, but requires an array of clinical data (age, gender, smoking status, blood pressure, cholesterol levels, etc.). According to the authors, the use of machine learning to identify intestinal dysbiosis characteristic of cardiovascular disease has very promising diagnostic potential in the context of routine check-ups.

The equilibrium between “good” and “bad” microbiota bacteria can be disrupted by many different phenomena. This imbalance, 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.   ) , can cause many diseases of varying severity. Fecal transplant (also called fecal bacteriotherapy) is a possible therapeutic solution.

Fecal transplant: a centuries-old solution

Fecal transplant is a very old treatment, since it was already being carried out in China in the 4th century! Its effectiveness was only recognized by European learned societies in 2013. To date, it has only been indicated in recurring C. difficile pathogenic bacteria infections, which it cures in 90% of cases. 
However, the involvement of microbiota in numerous other diseases (Inflammatory Bowel Diseases, diabetes, obesity, neuropsychiatric disorders, etc.) suggests that indications for fecal transplant could soon be expanded.

The procedure

Once selected, the donor prepares by taking laxatives. Their stool is then diluted in a sterile solution and filtered to be administered to the recipient. The recipient ingests a preparation similar to that used for colonoscopies in order to eliminate the disrupted microbiota.
There are several administration routes for the stool: the introduction of a probe through the nose to the stomach or duodenum, colonoscopy, enema, or, more rarely, ingestion of gastro-resistant capsules. It is up to the patient to decide with their doctor which route best suits their situation.

The Biocodex Microbiota Institute is dedicated to education about human Microbiota for General Public and Healthcare Professionals, it doesn't give any medical advice.

We recommend you to consult a healthcare professional to answer your questions and demands.

Bear this in mind before embarking on a trip to Mars: space missions aren’t all fun. Microgravity can atrophy idle muscles and subject bones to early osteoporosis; gastrointestinal transit slows down; altered day-night cycles disrupt sleep; and isolation affects mental health. If that’s not enough, the gut microbiota becomes unbalanced and the skin, nose and tongue microbiota start to mimic those of other crew members. Is this all connected? Might the microbiota alterations contribute to other imbalances? A recent review focusing on astronauts’ health suggests so.

Microbiota: the central factor?

We know the microbiota produces short-chain fatty acids (SCFAs¹), small molecules that affect appetite and satiety. Turned upside down by life in space and subjected to a fiber-depleted diet, the gut flora may accordingly inhibit astronauts’ appetite by synthesizing appetite-suppressant compounds. In addition, an alteration of the gut microbiota may reduce absorption of vitamins and minerals and play a role in the deterioration of the musculoskeletal system. Psychomotor functions and neurocognitive performance also deteriorate with time in space and these too may be under the influence of the gut microbiota, which acts on mood, stress, cognition, behavior, among others. Even the decline in astronauts’ immune functions may be partly explained by changes in the microbiota.

Helping out the microbiota

Therefore, space travel significantly modifies astronauts’ microbiota, particularly their gut microbiota. This may have an impact on their bone and muscle health, their metabolism and their immune system, and may even affect their nerves. Should we help nourish their microbiota using prebiotics or introduce beneficial bacteria via probiotics? The question is worth asking and future clinical trials may provide the answer.

^{1. Short Chain Fatty Acids}

Standard therapies designed to deprive the body of androgens, which are responsible for the growth of prostate cancer, are not always effective. In such cases, abiraterone acetate (AA) is used, and unlike other treatments, it is taken orally. Since AA is poorly absorbed, a significant portion of it is excreted in the stool and interacts with the gut microbiota. Several studies have highlighted the role of the gut microbiota in the development and progression of certain cancers, and in the effectiveness of treatments. However, there are still few data on the gut microbiota’s role in prostate cancer. The researchers therefore sought to show how AA (highly effective in hormone-refractory prostate cancer) affects the gut microbiota, and to assess whether the latter can influence responses to treatment.

Androgen deprivation remodels the gut microbiota

To this end, they used 16S rRNA sequencing to examine the gut microbiota composition of 68 prostate cancer patients divided in three groups:

- treatment-naive patients (n=33) ;

- patients receiving standard therapy (n=21) ;

- patients receiving standard therapy + AA (n=14)

Compared with the control group, standard therapy alone or standard therapy combined with AA led to a significant reduction in Corynebacterium, pro-inflammatory bacteria that metabolize androgens such as testosterone. AA intake led to a significant enrichment of Akkermansia muciniphila and increased production of vitamin K2, known for its anti-tumor properties.

A. muciniphila plays a key role in response to treatment

These results were confirmed in a simulated gut model, which excluded the possibility of immune involvement. Further investigations revealed that AA is metabolized by gut bacteria. Compounds derived from this degradation selectively impact the gut microbiota, characterized by the growth of A. muciniphila. This bacterial species known for its health benefits and anti-inflammatory properties is thought by the authors to play a key role in treatment response. Previous work had brought to light its beneficial role in responses to certain immunotherapies. This study highlights the gut microbiota’s key role in responses to an oral anti-cancer treatment, via mechanisms yet to be elucidated. Exploring drug-microbiota interactions could improve treatment outcomes for numerous diseases.

Rigorous monitoring of food intake is often required to avoid the infamous post-diet yo-yo effect. But is there another solution? As it happens, transplanting to yourself your own gut microbiota acquired following the diet may do the trick. The idea certainly seems a little off-putting since it involves ingesting the microbiota present in the feces via capsules. It has shown promise, nonetheless.

A two-step “slimming program”

Let’s start from the beginning. Obese patients were subjected to an exercise program and one of the following three diets: the classic guidelines; the Mediterranean diet plus a handful of nuts (rich in polyphenols); or a “green” Mediterranean diet (less meat, more fish, and lots of vegetable products with a high polyphenol content, e.g. Mankai duckweed and green tea). Six months later, 90 participants had lost an average of 8.3 kilos. The researchers then prepared capsules containing the microbiota in their stool. Over the next eight months, 44 of the patients took capsules containing their own fecal microbiota, while the remaining 46 were given a placebo.

A controlled yo-yo effect

The results? Patients who followed a green Mediterranean diet and then took capsules containing their own microbiota regained only 1.6 kg in the eight months post-diet, whereas those who followed the same diet but received a placebo regained 3.6 kg. Members of the first group also maintained their waist size and insulin level (hormone that controls blood sugar level), an effect not observed for the other two diets.

Effect of green Mediterranean diet on microbiota

Ultimately, the green Mediterranean diet had the most significant effect on the gut microbiota and bodily functions. When followed by the regular ingestion of the microbiota present in the gut on its completion, this diet has the potential to profoundly modify the gut microbiota and limit the yo-yo effect. Specific bacteria and changes in sugar transport may be the cause.

Obviously, this experiment should not be tried at home!