IBDs or chronic inflammatory bowel diseases, particularly Crohn's disease and ulcerative colitis, are a group of chronic illnesses with alternating phases of flares and remission. They are linked to changes in the gut microbiota, combining a decrease in bacterial diversity with a reduction in the abundance of certain species. However, more and more studies support the idea of a simultaneous change in the virus population which is also found in the gut, in the form of an overall change in their diversity and a specific increase in harmful viruses.

Abundance of “killer” viruses

To identify the viruses involved in IBDs, an international team studied the gut microbiota of patients with Crohn's disease or ulcerative colitis during both outbreaks and remission, as well as the microbiota of control subjects. The results show that 70% of control subjects share two major groups of viruses that form a “viral core” which is absent during illness. In its place are a multitude of temperate bacteriophages, fearsome viruses that destroy good bacteria, which may explain the lower bacterial diversity observed in the gut microbiota of patients. The authors also found differences between the two diseases. For example, changes in the viral and bacterial composition of the intestinal microbiota are greater in patients with Crohn's disease; in patients with ulcerative colitis, there are very few changes between flares and remission phases, with no clear explanation as to why this is so.

New approach

The joint analysis of bacteria and viruses in the gut microbiota helps us understand the changes associated with inflammatory bowel diseases. This approach may eventually lead to the development of biomarkers that are useful for diagnosis and of new therapeutic strategies.

Colorectal cancer (CRC) is one of the most common malignant conditions worldwide and is associated with a high mortality rate. It seems to result from complex interactions between the host and its environment: stress factors seem to cause alterations to the DNA of the colon cells involved in the onset of cancer. One of the suspected factors is gut dysbiosis.

Results in mice…

A French team studied DNA alterations in 136 mice with no microbiota, which received, via fecal microbiota transplant (FMT), samples of fresh stools from either 9 patients with CRC, or 9 other individuals with normal colonoscopy results. Seven weeks after the FMT, the mice which had received the CRC stool samples presented slight inflammation. An examination of their colon at 7 and 14 weeks revealed more precancerous lesions, known as aberrant crypt foci, with a greater number of hyper-methylated genes. Some bacterial species proved to be associated to precancerous lesions (Firmicutes, Clostridia), as well as a lower abundance of types of bacteria known for their anti-inflammatory effects or butyrate-producing bacterial species.

…confirmed in humans

In order to determine if gene methylation observed among the mice was also associated with gut dysbiosis in humans, the team analyzed the tissue, blood and stools of the 18 CRC and control patients from the initial experiment. This confirmed the correlation between the composition of the microbiota and the level of epigenetic alteration to the DNA: the levels of methylation of 3 genes proved to be discriminatory between the healthy patients and the CRC patients.

Immediately afterwards, a simple and reproducible blood test, aiming to diagnose colorectal tumors at an early stage among asymptomatic patients, was devised based on the calculation of a Cumulative Methyl Index (CMI) of certain specific genes. It was validated in a pilot study that included 266 individuals (95% specificity (sidenote: Specificity Ability to detect only those with the disease (to obtain the fewest false positives) ) , 59% sensitivity (sidenote: Sensitivity Ability to detect all those with the disease (to obtain the fewest false negatives) ) ), and was later confirmed in a prospective study of 999 asymptomatic individuals who were to have a colonoscopy (97% specificity, 43% sensitivity).

A CRC marker?

This work suggests that dysbiosis associated with CRC could promote carcinogenesis via epigenetic dysregulation of the genome. According to the researchers, the CMI for certain genes could constitute a marker for CRC; it could even predict the individual efficacy of prebiotic supplementation among individuals presenting a moderate risk.

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.

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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.