Nowadays, more than half the population lives in cities, and this proportion should exceed two-thirds by 2050. Massive urbanization leads to lifestyle changes in several areas: diet, housing architecture (use of more industrial and less natural materials), lesser exposure to the outside environment, to animals or parasites... Simultaneously, the frequency of metabolic and autoimmune disease has soared while the diversity of the human microbiota has dropped. Is there a causal link between the two?

From the jungle village to the big city

Based on this hypothesis, an American team tried to measure the impact of urbanization on the microbial composition (mainly yeasts and bacteria) on dwellings and its occupants. Their study focused on four sites in Brazil, with 4 different levels of urbanization, ranged from lowest to highest: Checherta, a village in the middle of the jungle; Puerto Almendra, a rural village; Iquitos, a town; and Manaus, a large city. The analysis of chemicals and microorganisms found on the homes’ walls, floors, beds, tables, and the analysis of the microbiotas (skin, nose, mouth, gut) of the owners and their pets allowed the researchers to demonstrate that microbial profiles were very diverse from site to site.

Very diverse microbial profiles

In cities, dwellings are characterized by the presence of chemical substances derived from drugs, detergents and shower gels, reflecting urban habits. They also contain more yeasts, probably because of the favorable conditions for their development (heating, less natural light, higher CO2 rates) and their lower sensitivity to antimicrobial agents. There are more bacteria of cutaneous origin and less environmental microorganisms. As for people, urbanization as well as rising living standards lead to a decrease in microorganism diversity. According to the authors, all these results shed light on the functional links between lifestyle, microbiota and health. In conclusion, our microbiota and our homes would benefit from a higher exposure to microbes from the outside environment and to materials of natural origin.

The aim of this Finnish case-control study was straightforward: to assess the impact of exposure to antibiotics on the risk of developing Parkinson's disease (PD). While it is known that patients with PD show alterations in the gut microbiota and that antibiotic exposure can affect the composition of the microbiota, a potential link between antibiotic exposure and the risk of PD has never been studied.

Case-control study

The team identified all patients diagnosed with PD in Finland between 1998 and 2014 (13,976 individuals) and compared their purchases of oral antibiotics between 1993 and 2014 with those of 40,697 control subjects. The study found correlations between antibiotic use and the risk of PD, the highest being observed for macrolides and lincosamides. These antibiotics are excreted by bile and, therefore, can be found in high concentration in the feces and are responsible for profound and lasting changes in the microbiota: patients who had purchased five of these antibiotics had a 42% increased risk of developing PD within 10 to 15 years, a delay typically observed between the onset of peripheral lesions and the first motor signs. However, in the authors' own opinion, this link remains open to criticism, since it did not stand up to the Benjamini-Hochberg procedure for controlling the rate of false positives (False Discovery Rate or FDR).

Strong correlation for certain antibiotics

On the other hand, even after FDR correction, between one and four antibiotics with anti-anaerobic effects were associated with a 14% increased risk of PD in the 10-15-year period. Based on previous results, this time period may correspond to an alteration of microbiota followed by a cascade of physiological events leading to the first peripheral lesions and diagnosis some years later. Similarly, the use of tetracyclines (10 to 15 years earlier), or sulphonamide and trimethoprim (1 to 5 years earlier) were highly correlated with PD. Lastly, taking antifungal medications also increased the risk of PD, by up to 26% for two purchases in the previous 1 to 5 years. Therefore, the links between antibiotic use and the risk of PD vary according to the class of antibiotics and are stronger for those with anti-anaerobic effects. In addition, a positive correlation was observed between the use of broad-spectrum antibiotics and the risk of PD.

Alteration of the microbiota?

According to the authors, since the gut microbiota is mainly composed of anaerobic bacteria, anti-anaerobic and broad-spectrum antibiotics are those most likely to have a strong impact on its microbial population. This supports the still tentative idea that an alteration of microbiota by antibiotics explains the link between antibiotic usage and risk of PD.

Fecal microbiota transplant (FMT) is now a recognized treatment for recurrent Clostridium difficile infection (CDI), but it is not thriving the way it should. This could be due to the lack of specialized centers, difficulties to recruit donors or complexity of procedures. By reducing hospital administrative burden, stool banks could help the widespread adoption of this technique. However, their legislation, organization and structure are too diverse to provide everyone with the same guarantees.

Around thirty experts came together to establish a single definition of stool banks and prepare a Good Practice Guide. After reviewing the scientific literature, they reached a consensus on 6 topics: 1) general principles of FMT and stool bank; 2) selection and screening of donors; 3) collection, preparation and storage of stools; 4) services and clients; 5) records, result monitoring and ethical issues; 6) update of clinical applications of FMT.

The Biocodex Microbiota Institute is dedicated to educate 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.

Fibromyalgia (FM) is one of the most common forms of chronic generalized pain, with an estimated prevalence of 2–4% in the adult population. FM is characterized by pain, tiredness, sleeping difficulties and cognitive symptoms. Since there is no objective diagnostic criterion other than these symptoms, FM causes a significant deterioration in people’s quality of life. The growing understanding of the interactions between the gut microbiota and the central nervous system, also known as the “gut–brain axis”, suggests that it may also affect pain processing and perception. To better understand the pathophysiology of FM, the gut microbiota of 77 Canadian women suffering from FM (on average, aged 46 years and diagnosed 12 years earlier) and of 79 control subjects (11 first-degree relatives, 20 members of patients’ households and 48 unrelated controls) were compared based on the analysis of 16S rRNA and whole genomes

Taxa associated with the severity of FM

No difference was observed between FM patients and healthy subjects in terms of diversity and overall structure of the microbial population. However, closer examination showed an association between the abundance of several taxa and the severity of symptoms linked to FM, including pain intensity, pain localization, tiredness, sleep disorders and cognitive symptoms.

A specific signature

The comparison of patients and control subjects also revealed a specific signature in the fecal microbiota of FM patients: 19 species were identified–some relatively less abundant in FM patients, while others were more abundant. Several are involved in the metabolism of butyrate and propionate, two short-chain fatty acids. The serum concentrations of these fatty acids are altered in FM patients, who have higher levels of butyrate and lower levels of propionate. These fatty acids could be involved in the mechanisms linking the dysbiosis and the symptoms observed. Finally, certain taxa in FM patients are also observed in other dysfunctional syndromes–irritable bowel syndrome, chronic fatigue syndrome, interstitial cystitis–while others seem to be specific to FM.

An identification algorithm?

Beyond a better understanding of FM, or even potential therapeutic applications, the researchers also open the path to a possible diagnostic test for FM patients. A machine learning (sidenote: Machine Learning an artificial intelligence technology that allows computers to learn solely on the basis of a very large collection of data )  algorithm based only on the composition of the microbiota seems able to distinguish FM patients from control subjects with a prediction accuracy of 87.8%.

Alcoholic hepatitis is the most severe form of alcoholic liver disease and is associated with a mortality rate of 20 to 40% within 1 to 6 months. Although it is known that the gut microbiota can promote ethanol-induced liver diseases in mice, the microbial factors responsible for this process remain poorly understood. Hence the interest in the results published in Nature on the role of the microbiota in transmission and progression of this disease.

Cytolysin-secreting E. faecalis

The research shows that patients with alcoholic hepatitis exhibit a specific fecal microbial composition, namely having 2,700 times more Enterococcus faecalis, a bacterium found in the stools of 80% of patients. However, certain “cytolytic” types of these bacteria produce an endotoxin called cytolysin which acts against eukaryotic cells as well as against Gram-positive bacteria. The presence of cytolytic E. faecalis bacteria seems to be correlated to the severity of the liver disease and patient mortality.

From cytolysin to hepatic lesions

Gavage of mice subjected to a high ethanol intake diet (or to a control isocaloric diet without ethanol), with either cytolytic or non-cytolytic strains of E. faecalis, confirmed that cytolytic E. faecalis induced more hepatic lesions, steatosis and inflammation, and led to a more rapid death. This bacterium was also found in the livers of all mice subjected to a regimen with alcohol, but not in the liver of the control mice, suggesting that ethanol is required for translocation of E. faecalis from the gut to the liver.

A protective bacteriophage

The researchers then studied the therapeutic effects of a bacteriophage targeting cytolytic E. faecalis in mice receiving gavage with strains of E. faecalis responsible for hepatic steatosis. The bacteriophages reduced cytolysin levels in the liver of the rodents and eliminated their ethanol-induced hepatic lesions. The researchers then studied mice colonized with bacteria from stools of patients with alcoholic hepatitis. Administration of bacteriophages suppressed the onset of hepatic lesions and steatosis, and led to a decrease in the content of Enterococcus.

A future treatment?

These results not only established a link between the cytolytic E. faecalis bacterium and the severity and mortality rate of alcoholic hepatitis, they also showed that a bacteriophage can target the bacterium specifically, and so provide an alternative to antibiotics. Nevertheless, clinical studies are still required to prove the validity of cytolysin as a biomarker in human subjects, and to confirm that bacteriophages represent a safe and effective therapeutic approach.

Urinary tract infections poison the life of 150 million people worldwide every year and are mainly caused by Escherichia coli. The gut microbiota acts as a reservoir for this uropathogenic bacterium of the Enterobacteriaceae family: when excreted in the stools, it colonizes the periurethral region and infects the urinary tract. Despite inconsistent results regarding their efficacy, it is advised to eat cranberries to prevent relapses. These small red berries seem to deplete this reservoir of enterobacteria that are responsible for urinary infections by acting as a prebiotic or antimicrobial agent on the gut microbiota.

Cranberries: pure or in extracts

To determine which components are at the origin of this effect, an American team analyzed the impact of 44 active ingredients found in cranberries on the bacterial profile of the human gut microbiota. To this end, the researchers used a simulator replicating the human microbiota, that was created using stool samples with an increased or decreased content of enterobacteria. They then daily inoculated either cranberry powder, or extracts spiked with or deprived of polyphenols. According to several in vitro studies, the antimicrobial or anti-adhesive properties of polyphenols could explain the efficacy of cranberries to prevent urinary tract infections.

Salicylate was the most active component

After five days, the researchers observed an increase in the number of beneficial bacteria within the gut microbiota, and a decrease in the number of enterobacteria in all samples. The most notable changes were observed with cranberry powder, which suggests that all components–polyphenols and other molecules– act together to change the microbiota. However, salicylate is the component that proved to be the most important. One question that remains is whether this is due to its antimicrobial or its prebiotic effect on the enterobacteria responsible for urinary tract infections.

When a virus enters the digestive tract and is about to infect intestinal cells, it is not alone: billions of bacteria from the microbiota are also there and can modulate its infectious potential. Scientists arrived at this conclusion accidentally while working on Rag1-KO mice, a model of immunodeficient mice with chronic rotavirus infection (RV).

The microbiota as a barrier against rotavirus

These researchers non-intentionally observed the birth of a line of RV-resistant mice, which they called GSU mice (sidenote: GSU stands for Georgia State University, where these mice were born ) . They then tried to understand the origin of this resistant phenotype. When Rag1-KO mice were fed the feces of GSU mice, they became resistant to RV, thus proving the role of the microbiota of GSU mice.

A segmented filamentous bacterium is involved

A series of discriminating treatments (heat, filtrations, several antimicrobial agents) complemented by an analysis of the microbiome of GSU mice indicated the specific presence of Candidatus arthromitus species, which is a segmented filamentous bacterium (sidenote: Bacteria from the Clostridiales family, that colonize the gut of many species )  (SFB). This presence was confirmed through electron microscopy at the ileum level. In vitro, the SFB strain had the same ability as GSU mice feces to reduce the infection of epithelial cells by rotavirus. In vivo and isolated from the microbiota, it still provided, by itself, a protection against RV to immunosuppressed germ-free mice, and reduced the incidence of diarrhea in newborn non-immunodeficient mice, thus proving its own protective effect.

A new non-immune mechanism

Contrary to the researchers’ initial hypothesis, no known immune mechanism mediating the resistance to RV was involved (neither IL-22/IL-17 nor interferon λ). Several non-immune pathways could coexist: SFB could degrade a surface compound of RV and prevent it from interacting with the epithelium. But the main underlying mechanism seems to be located on the host side: the renewal of villi epithelial cells could be accelerated under the influence of SFB, thus causing the quick expulsion of cells potentially infected by RV. The microbiota could thus become a key pool to develop new strategies against viral infections.

Our gut microbiota is dominated by two groups of bacteria, Bacteroidetes and Firmicutes, with a relatively stable ratio. A disruption in this balance (dysbiosis) opens the way to the development of a variety of disorders (inflammatory or infectious diseases) and even obesity. On the contrary, a balanced microbial composition is a key element of an individual’s wellness and good health. Among the main architects of our gut flora, food is by far the most active. But it seems that what we drink is just as important.

Key role of polyphenols

Besides water, tea is the most consumed beverage in the world. Its high content in polyphenols reduces the number of some pathogenic bacteria and prevents their growth. To accurately determine the full range of effects of tea on gut bacteria, two English researchers reviewed the scientific literature on this subject. According to the results, daily consumption of green tea (between 400 and 1000 ml) favorably modifies the composition of our microbial ecosystem, leading to changes that support the Bacteroidetes/Firmicutes balance. By preventing dysbiosis, tea could counteract the negative effects of obesity or high-fat diet, which could explain why, in several studies, its consumption is associated with weight loss. Although most studies focused on green tea, those dedicated to black tea or less well-known types of tea such as Fuzhuan, Pu-erh or Oolong, revealed similar benefits.

Further studies are required

It is now necessary to understand how the different teas impact the gut microbiota and what regular consumption levels are required in healthy adults with normal weight. The role of tea consumption to alleviate symptoms of some gastrointestinal disorders needs to be further analyzed, according to the researchers.

Recommended by our community

How can we specifically target pathogenic bacteria without creating resistance or inducing collateral damages to other members of the microbial community, and with a simple yet effective tool. A team from London may have found a solution, based on CRISPR-Cas9, i.e. “molecular scissors” that can implement gene corrections: a guide RNA recognizes a DNA sequence (called CRISPR) to which Cas9 nuclease binds, and cuts the target sequence. And we know that any cut into circular bacterial DNA prevents its replication and induces cell’s death.

A plasmid vector

The idea behind this study is the following: instead of inserting Cas9 into the bacterial DNA, researchers inserted it into a plasmid, a small DNA component present in addition to the bacterial genome. What is the advantage? Bacteria spread these plasmids through a process called conjugation (sidenote: Conjugation The donor bacterium binds to the recipient, transfers it a strand of the plasmid DNA which will later be transformed again by the recipient into a double-stranded plasmid ) , even between different species. But until now, studies were restricted by the low frequency of these plasmid transfers. This deficiency was overcome by the development of a plasmid containing not only Cas9 nuclease but also any equipment necessary to the conjugation process. Thanks to the successive conjugations between bacteria (the recipient becoming the donor, and so on), this new plasmid spreads very quickly, from an E. coli (donor) population to a nearly 100% Salmonella enterica population, considering that the closer the contact between cells (for instance in a biofilm), the greater the conjugation frequency. It should be noted that this propagation is possible because the expression of Cas9 is controlled: arabinose is required for nuclease expression and thus for bacterial killing. In the absence of arabinose, the plasmid is only able to spread.

Target: non-essential genes

Plasmid efficacy to kill target bacteria still had to be assessed, by varying one parameter: the gene cut by nuclease. The researchers thus tested 65 fragments of guide RNA, each recognizing a different gene of the bacterial DNA of S. enterica–some essential and some non-essential. By using E. coli again as initial donor of the plasmid, the team found that S. enterica mortality rate varied from 1 to 100%, depending on the target gene. Although questions remain to explain these differences, targeting essential genes seems less efficient: this gives rise to the insertion of DNA fragments into the plasmid, which then loses its ability to kill bacteria. This does not happen with non-essential genes.

A solution to reach biofilms?

Even though the model is only based on 2 tested species, the plasmid could theoretically be transferred to a complex microbial community: the conjugation could therefore be no longer the limit. The researchers must now focus on the plasmid efficacy and parameters impacting its activity. This process could have a wide range of applications, including the penetration of biofilms which are difficult to reach through other vectors: a native bacterium of the biofilm could be the initial donor, thus allowing the plasmid to spread very quickly and destroy target bacteria, even the most resistant to antibiotics.

The feeding method will directly influence the composition of the gut microbiota of newborns. The gastrointestinal tract of breastfed newborns contains more bifidobacteria and lactobacilli than that of formula-fed babies. But how is the microbiota of breast milk modulated? Several studies indicate that the mother’s diet during pregnancy and lactation has an influence on its composition. And more recently, another hypothesis suggests that bacteria found in the mother’s gut microbiota migrate to the mammary gland.

Two dominant bacterial genera

To get a clearer picture, a team of Brazilian researchers analyzed the microbial composition of breast milk from 94 women who recently gave birth. Among the 85 identified bacterial genera, 3 were systematically present and 10 were found in the composition of at least 90% of milk samples analyzed. Two genera were largely dominant: streptococci and staphylococci, which are believed to trigger the colonization of the gastrointestinal tract of babies. Bifidobacteria and lactobacilli, which are abundant in the gut microbiota of breastfed babies, were also present but in lower amounts.

Effect of vitamin C and polyunsaturated fatty acids

The researchers then examined the effects on the microbiota of diet during pregnancy and during the first month of breastfeeding. Their two main findings were:

- Only the consumption of vitamin C during pregnancy was associated to a specific bacterial profile, dominated by staphylococci, suggesting that is has an impact on the microbiota of breast milk.

- The consumption of polyunsaturated fatty acids (Salmon, tuna...) during the lactation period slightly modulated the abundance of bifidobacteria.

A different influence before and after delivery

A woman’s diet seems to have an effect on the microbial diversity of her milk. But this influence appears to be stronger during pregnancy than during the lactation period.