Tiger mosquitoes (also known as Aedes albopictus) originate from Southeast Asia but have quickly spread to all continents. Only the Antarctic has been able to resist to this invader! The female’s ability to transmit no less than 19 viruses (including dengue, chikungunya, zika) makes it a true health scourge against which urgent action is needed.

Attracted by some skins

We know that tiger mosquitoes are attracted, among other substances, by human sweat. But not any sweat: some people are systematically stung while others are totally ignored by these blood suckers! This injustice could be due to the concentration of some volatile components in the sweat (lactic acid, acetone...) which are responsible for the skin odor. However, these components are secreted both by sebaceous glands and bacteria from the cutaneous microbiota. The composition of the latter could thus be at the source of the attraction of tiger mosquitoes towards some individuals.

Variable power of attraction

A French team wanted to identify the components associated to the power of attracting or repelling female tiger mosquitoes in bacteria from the skin microbiota of 12 volunteers. First, they discovered that three bacteria naturally present in our skin flora attract insects (Staphylococcus saprophyticus, Klebsiella rhizophila and Kylococcus sedentarius), while two others repel them (Corynebacterium tuberculostearicum and Staphylococcus hominis). Then they observed that two molecules were associated to attracting species, but only when they were secreted in high quantities; in lower quantities they were, on the contrary, associated to one of the two repelling bacteria.

New odor-baited traps

According to the authors, these discoveries could open the way to the development of new prevention methods of tiger mosquito bites intended to stop the growth of “attractive” bacteria or modify their ability to produce volatile components which attract insects.

Clostridioides difficile (sidenote: Clostridioides difficile formerly Clostridium difficile )  infection (CDI) affects about 450,000 people and causes 30,000 deaths per year in the United States. It is responsible for a substantial proportion of deaths attributable to antibiotic-resistant bacteria. CDI arises following the ingestion and adhesion of spores, which then germinate and turn into vegetative forms of the bacterium that colonize and secrete toxins responsible for a wide spectrum of symptoms ranging from diarrhea to life-threatening pseudomembranous colitis. But a carrier may also be completely asymptomatic and CDI may show its pathogenic potential only once antibiotics are taken.

Establishing a list of metabolites

C. difficile is considered as an opportunistic colonizer that might be eradicated by healthy intestinal microbiota. Several metabolic functions are believed to contribute to this eradication. To better understand the link between gut metabolites and CDI in humans, a research team studied the fecal metabolomic profiles of 186 hospitalized patients with symptoms of diarrhea: 62 patients with CDI (positive toxigenic culture and positive enzyme immunoassay), 62 patients with positive toxigenic culture but negative enzyme immunoassay, and 62 matched non-colonized controls (negative toxigenic culture and negative enzyme immunoassay). Fecal metabolites were characterized by gas chromatography.

Two metabolic signatures

Among the 2,463 metabolites detected in the stools, 43 can be used to discriminate between patients with CDI and non colonized controls. Many of them are derived from the Stickland fermentation pathway (sidenote: The Stickland fermentation pathway coupled redox reaction of two amino acids, one playing the role of hydrogen acceptor, the other of hydrogen donor. It occurs in many Clostridium species de Vladar HP. Amino acid fermentation at the origin of the genetic code. Biol Direct. 2012 Feb 10;7:6. ) , in which bacteria, such as C. difficile, use amino acids as substrates. The strongest association found was for a short chain fatty acid resulting from leucine fermentation, which was found in significantly larger quantities in patients with CDI. The team also identified a number of secondary bile acids significantly less abundant in patients with CDI, and derived from the dehydroxylation by gut bacteria of primary bile acids which are synthesized and conjugated by the host. It remains unclear whether these dehydroxylated bile acids are only biomarkers of CDI-negative patients, or if their formation protects them from CDI by inhibiting spore germination, for instance.

Towards a more precise diagnosis?

Eventually, these results could lead to the definition of a specific metabolomic profile for CDI and refine patient diagnosis, by reducing false positives related to inactive spore detection by toxigenic culture, and false negatives caused by the poor sensitivity of the enzyme immunoassay.

Koalas are discriminating gourmets. Maybe a little too much, since many of them only tolerate leaves from white gum trees (Eucalyptus viminalis). That is why they are vulnerable to starvation in case of scarcity. Nonetheless, some of them can feed from other species of eucalyptus, especially messmate (Eucalyptus obliqua) which is more fibrous and less nutritious but very widespread. This difference led Australian researchers to study a potential link between the composition of marsupials gut microbiota and their ability to digest the components of the leaves from these two trees.

Link between microbiota and diet

The comparison between the gut microbiota of koalas who only eat white gum leaves or only messmate leaves confirms there is a difference in their gut microbiota composition: the latter present a higher content of species from the Lachnospiraceae and Ruminococcaceae families, which are bacteria known to promote the degradation of cellulose, more abundant in the intestines of messmate-eating koalas.

Unchanged microbiota

Koalas preferring white gum leaves and held in captivity were given alternately leaves of both eucalyptus species. The objective was to assess whether a change in diet would lead to a change in the composition of the gut microbiota. This phenomenon, frequent in any animal species and in humans, was not observed here. This is the proof that koalas have a low microbial adaptability to dietary changes, which can explain why they reject some leaves.

Towards a probiotic for the survival of the species?

However, the administration of fecal matter capsules from wild messmate-eating koalas to koalas eating exclusively leaves from white gum trees changed the gut microbiota of the recipients and allowed them to eat other species of eucalyptus. Eating habits then evolved over time: as the gut microbiota became more similar to that of donors, these marsupials tended to eat more messmate leaves. Therefore, a probiotic approach through fecal transplant could prove useful in helping koalas adjust to a new environment or to the increasing scarcity of their favorite leaves, thereby ensuring their survival.

How does the gut microbiota modulate immune functions? This question still remains unanswered by science, although a subset of T cells might be involved, namely MAIT (mucosal-associated invariant T) cells, which take part in the gut mucosa homeostasis. MAIT cells are non-conventional T cells having an innate function, mainly located in gut mucosa: they include an invariant pattern-recognition receptor for bacterial metabolites.

Proposed mechanism

In an article published in Sciences, French teams summarized their different works which tend to show that, in mice, gut bacteria react to the development of MAIT cells in the thymus, where T cells reach maturation. The proposed mechanism, based on in vitro and in vivo experimental results, is the following: gut bacteria secrete a metabolite of the biosynthetic pathway of B2 vitamin called 5-OP RU. 5-OP-RU quickly crosses the gut mucosa and travels to the thymus where it is recognized by the receptors of immature MAIT cells. This recognition could induce multiplication and maturation of MAIT cell precursors. Mature MAIT cells would then leave the thymus and reach mucosa, especially the gut mucosa, where they could strengthen the epithelial barrier, curb the development of bacterial populations and participate in the defense against pathogens. It should be noted that 5-OP-RU might not be the only bacterial metabolite involved: the researchers suspect that other mediators induced by the gut microbiota also play a role in the multiplication and control of MAIT cells.

The microbiota: an integral part of the immune Self?

By proposing a new mechanism explaining how the gut microbiota could remotely influence the host’s organs, this publication also participates in decoding the complex dialogue that emerges between the microbiota and the immune system, and specifically between the gut microbiota and the thymus, regarded as the place where the distinction between the Self (by suppressing lymphocytes able to recognize the Self, thus avoiding autoimmune diseases) and the Non-Self (positive selection of lymphocytes recognizing foreign components) is made. But according to the proposed mechanism, MAIT cell maturation within the thymus has the distinguishing feature of being based on microbiota metabolites. This suggests that the gut microbiota could be an integral part of the immune Self.

Health benefits of red wine–as long as it is consumed in moderation–would be mainly due to polyphenols contained in it. They are natural components that are mainly found in the skin of red grapes and whose antimicrobial properties could have beneficial properties on the gut microbiota, according to studies conducted on animals. Was the same phenomenon observed in humans? What about other types of alcohol?

More diversified gut microbiota

To answer these questions, a team of London researchers studied the effects of beer, cider, red wine, white wine, and liquor, on the gut microbiota of 916 British female twins. Based on the analysis, they observed that the gut microbiota of women drinking red wine was significantly more diverse than those who drank other types of alcohol. A large bacterial diversity is one of the signs of good health. The results were confirmed in two other cohorts (American and Dutch), each including about a thousand subjects.

Role of polyphenols

Greater microbial diversity, which was only found with red wine, could be explained by the high content of polyphenols in this alcoholic beverage: it is 6 to 7 times higher than in white wine, for instance. Moreover, according to the authors, a very low consumption is enough to produce these effects. Another surprising result at first glance is that red wine consumers also had a lower body mass index, across all cohorts.

Could the “French paradox” be soon resolved?

According to the authors, the increase in bacterial diversity could partly contribute to the benefits obtained from moderate consumption of red wine by improving the metabolism of cholesterol or by reducing the body fat rate. This discovery should make red wine–and ink–flow as the very controversial debate over the benefits of this popular beverage continues. Could we soon be able to solve the “French paradox”?

Pancreatic ductal adenocarcinoma (PDAC) is a dreaded cancer. As it is usually detected late, its prognosis is grim, with a 5-year overall survival rate of 9%. The tumor microbiota seems to play a role in this survival rate, based on the numerous results published in Cell by 31 researchers–mainly Americans.

More diversity = longer survival

To understand the impact of tumor microbiota and immune system on the long-term survival rate, these researchers analyzed the composition of the microbiota of resected tumors in 68 patients with PDAC divided into two groups: 36 patients who survived more than 5 years (mean: 10.1 years) and 32 patients who died less than 5 years after the procedure (mean: 1.6 years). Their results put forward a larger diversity of bacterial species present in the tumor microbiota of patients who survived more than 5 years. These results were confirmed by researchers in a second cohort.

Immune modulation

Moreover, the authors highlighted that each one of the two groups of patients displayed a specific intratumoral microbiota signature: presence and abundance of 3 bacterial genera (Pseudoxanthomonas, Streptomyces, Saccharopolyspora) and of Bacillus clausii are able to predict the survival in 97.51 to 99.17% of cases (according to the cohort). Additional immunohistological analyses suggest that the composition of the tumor microbiota could have an impact on cancer development by modulating the anti-tumor immune response through the recruitment and activation of CD8 T cells.

From the intestines to the tumor

In parallel, the analysis of stools, resected tumor tissues and adjacent non-cancerous tissues of three patients showed that the gut microbiota represents about 25% of the tumor microbiota, while it is absent from adjacent tissues: the tumor microbiota could thus be colonized by the gut microbiota. Finally, fecal microbiota transplants (FMT) from three types of patients (long-, short-term survival or control) were carried out in mice. These works confirmed the ability of the gut microbiota to colonize pancreatic tumors. They also suggested its ability to modify the bacterial composition of the tumor and, in turn, to modulate the immune function, thus affecting cancer progression and patient survival. Besides the possibility of formulating a prognosis based on the tumor microbiota, FMT results give us hope that one day we will be able to manipulate this microbiota to improve life expectancy of patients with PDAC, for whom very few therapeutic options are currently available.

To identify the bacteria living in our intestines, the method more frequently used consists in collecting stool samples. Although this technique has the indisputable advantage of being simple and non invasive, it also suffers from an obvious limitation: it only offers a residual insight into the gut microbiota but it does not give an account of the very different populations living throughout our gastrointestinal tract.

Targeted sampling

But things could very well change soon. In July 2019, an American team announced the development of a 3D printable capsule, that, once ingested, could find out everything about the gut microbiota, or more precisely, the different gut bacterial populations. Once a protective layer is dissolved in the small intestine, this encapsulated mini-laboratory takes bacteria samples surrounding it based on a system that does not require batteries. The capsule follows the same path as food, carried by natural intestinal movements, but thanks to a magnet it can be precisely placed in the specific region to be studied. To avoid losing this technological marvel “on its way out”, it is colored with a specific dye that turns fluorescent under a UV lamp..

Clinical trials should be soon conducted in humans

Of course, the capsule was thoroughly studied, first in test-tube experiments (in vitro) and later in pigs and primates (in vivo), in order to confirm it was able to identify the different bacterial populations in the various digestive segments, as well as their relative abundance. The only thing left to do is to carry out clinical trials to determine whether the capsule could also be used in humans for clinical purposes.

Understanding the distribution of the microbiota

“We learn more and more about the role of the gut microbiota on health and diseases”, explained Sameer Sonkusale, Professor of Electrical and Computer Engineering at Tufts University, and co-author of the study. “However, we know very little about its biogeography”, i.e. the distribution throughout the gastrointestinal tract. “This capsule will make it easier to understand the role of spatial distribution of bacterial populations within the gut microbiota in order to develop new therapeutic strategies.”

While 50 to 75% of patients with Crohn’s disease will require at least one bowel resection during their lifetime, recurrence is observed in about 50% of them in the 5 years following their operation. Endoscopy is the gold-standard method to diagnose relapse. However, it can only be carried out a few months after the operation, thus delaying a potentially necessary early therapeutic intervention. The identification of early predictive factors of recurrence is thus of major interest.

Persistent dysbiosis

According to a multicenter study published in Gut and headed by Pr. Harry Sokol’s team, the microbiota present in the ileal mucosa could very well be one of these factors. To reach this conclusion, the researchers analyzed the composition of the microbiota extracted during bowel resection surgery (T_r), and later during follow-up endoscopy (T_s), in 201 patients. Result? Bowel resection caused a significant change in the microbiota in all patients and an improvement of the initial dysbiosis, but its effects were less pronounced in those who were relapsing. In the latter, between T_r and T_s, there was a decrease of alpha diversity, a more significant increase of several species from the Alphaproteobacteria class, and a lesser increase in some species from the Firmicutes phylum and the Lachnospiraceae and Ruminococcaceae families, which are believed to be markers of intestinal health.

Using the microbiota to predict recurrence

In modeling studies (some models take into account the factors modulating the recurrence risk: previous resection, tobacco use, male gender are aggravating factors while anti-TNF (sidenote: anti-TNF (Tumor Necrosis Factor) drugs are used to control inflammation. )  use is a protective factor), the researchers went further by identifying several taxa that are overabundant during the resection and that could be significant recurrence markers, especially bacteria from the Gammaproteobacteria class, Ruminococcus gnavus group and Corynebacterium genus. Despite some limitations, this study suggests that the composition of the microbiota at the time of bowel resection could predict recurrence and steer the postoperative therapeutic approach. There are however obstacles to the implementation of such an approach, especially the frequent preoperative use of antibiotics, which alter the microbiota and jeopardize its use as a predictive tool.

Parkinson’s disease affects more than 1% of people over 60. It is the second most frequent neurodegenerative disease in the world. Previous studies have established a link between gut microbiota disruption (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.   ) ) and the development of this disease through the gut-brain axis, but no definite conclusion has been reached regarding a specific bacterial composition associated to the disease.

Dysbiosis observed in patients with Parkinson’s

In recent studies conducted in 80 patients with several degrees of Parkinson’s, their gut microbiota was compared to that of 72 healthy persons. A dysbiosis was brought to light: the intestinal flora of patients displayed a higher abundance of bacterial species belonging to the Lactobacillaceae, Enterobacteriaceae and Enterococcaceae families, and a lower abundance of Lachnospiraceae. The more severe the disease was, the more apparent this difference as regards to Enterobacteriaceae and Lachnospiraceae, and the more important the motor disorders were. This is why researchers believed that these two bacterial families were correlated to the disease’s progression.

Neurotoxic inflammation

In the patients under investigation, the composition of the gut microbiota was affected by several parameters associated to the disease (duration, development stage, use of anti-Parkinson drugs), although they do not act on one specific bacterial family. The patients also displayed disrupted activity of neurotransmitters, i.e. molecules involved in mood regulation (serotonin, dopamine and norepinephrine); and they also produced more lipopolysaccharides, substances generating an inflammation that may damage neurons when they cross the intestinal barrier and the blood-brain barrier (that protects the brain from the surrounding blood). Although this scientific breakthrough is undeniable, it still needs to be further investigated (link between dysbiosis and gut inflammation, role of neurotransmitters in the gut-brain communication...).

Tumor formations in colorectal cancer (CRC) is an extended process, which explains why clinical signs only appear at an advanced stage of the disease, although it is curable when treated early. The gut microbiota is strongly suspected to be involved in this process, based on both genomic and metabolomic (sidenote: Metabolomic study of metabolites derived from the body or the environment and it takes place downstream from genomics (study of all genes), among others. ) data. Better understanding its role is thus important, from an etiologic and diagnostic perspective. That is why a Japanese team carried out metagenomic (N = 616) and metabolomic (N = 406) analyses on fecal samples from patients suffering from different stages of colorectal neoplasia and who underwent a colonoscopy. Patients were divided into nine groups: from the control group to CRC stage IV, through early stages such as multiple adenomatous polyps and intramucosal carcinoma (stage 0).

Changes in microbiota occurred from the early stages

Thanks to the advanced sequencing technique used (shotgun), the results revealed changes in the microbiota and the metabolome, not only in patients with advanced lesions but also at early stages. Two significant changes in the gut microbiota composition were observed during the development of CRC: on the one hand, a progressive increase in the relative abundance of some species (such as Fusobacterium nucleatum spp., Solobacterium moorei…), whichever the stage of the disease; and on the other hand, coexistence and increase of other species (such as Actinomyces odontolyticus), only in patients at an early stage. Moreover, increases in abundance of other species can characterize CRC progression, such as Parvimonas micra from stage I and Bilophila wadsworthia at stages III/IV.

The role of fecal bile acids confirmed

Significant differences at the metabolome level were also observed between groups that could be used to distinguish between healthy patients and those with a high risk of CRC. In patients with intramucosal carcinoma, significantly higher levels of branched chain amino acids (isoleucine, leucine and valine), phenylalanine, tyrosine and glycine were found. Bile acids, including deoxycholic acid, were significantly higher in all patients at an early disease stage, thus confirming the positive correlation already reported between fecal concentration of secondary deoxycholic bile acids and increased risk of CRC. All these results, obtained in a large cohort, show that changes happen in the gut microbiota as soon as warning signs of colorectal cancer appear, generating changes in fecal concentrations of some metabolites.