As the impact of the gut microbiota on our health is increasingly better documented, strategies able to favorably affect it are being developed, particularly through diet. Some researchers thus focus on foods specifically aimed at acting on the microbiota, or MDF (microbiota-directed foods), in this case, polysaccharides (plant fibers).

34 “fibers” were analyzed

A murine model led to a better understanding of how human gut bacteria interact with dietary polysaccharides, as well as with each other: germ-free mice colonized by beneficial gut bacterial strains (Bacteroides spp. from a slim adult male, that distinguish him from his obese twin) were fed different combination of 34 dietary fibers, in addition to a fiber low diet (representative of the typical American diet). By combining several cutting-edge technologies, the researchers identified the fiber bioactive compounds that promote the development of some Bacteroides species. Twenty-one out of 34 tested polysaccharides significantly improved the growth of some species, such as citrus pectin and pea fiber with Bacteroides thetaiotaomicron. These results could eventually allow us to increase the content of these active compounds in our diet.

Inter-species competitions

To understand the mechanisms at play and identify the fibers that are ingested or not, additional experiments were carried out using biosensors, i.e. magnetic beads coated with polysaccharides and easily recovered in the stools. They confirmed that 2 different bacterial species (for instance Bacteroides cellulosilyticus and Bacteroides vulgatus) are able to degrade the same polysaccharide, as long as they are equipped with the necessary genes. As a result, different strains compete for nutritional resources.

Towards personalized nutritional medicine?

By analyzing how gut microorganisms adapt to their environment (by counterbalancing the absence of a specific species or by competing with each other), the scientists observed that some bacteria were more flexible than others, as regards the use of the substrate. This is the case for Bacteroides ovatus, which is able to adapt to the presence of B. cellulosilyticus, its competitor for arabinoxylan (a major component of plant cell walls in cereals and peas), while B. vulgatus does not have this ability. Identifying which organisms are the most flexible helps us understand how some strains can coexist with the other “inhabitants” of the gut community. Based on these results, the team already foresees the development of personalized dietary guidelines based on microbiological and physiological data from the host obtained with biosensors.

A healthy vaginal microbiota is characterized by very low bacterial diversity and predominance of one or few lactobacilli species. On the contrary, high diversity and reduced levels of lactobacilli unbalance the flora, as is the case in bacterial vaginosis. It is a benign infection but it predisposes to sexually transmitted infections, urinary tract infections, and increases the risk of premature delivery. Although effective in the short term, antibiotics do not prevent relapses, which reach a 70% rate within 3 months. Could vaginal microbiota transplant be the solution?

Carefully screened donors

An American team had 20 female volunteers fill out a standard questionnaire with additional health and sex related questions (vaginal infections, number of partners, use of condoms, method of contraception...). After completing clinical and biological exams to determine their infectious status, the investigators analyzed the composition of their vaginal microbiota. This very careful donor selection protocol allowed them to determine the ideal graft: vaginal secretions with high content of lactobacilli leading to acidic pH and ensuring a better protection against infectious germs.

Strict inclusion criteria

The authors suggested to extend the screening process to many other infections in addition to those usually planned in standard transplants and also recommended several exclusion criteria: previous exposure to herpes virus, history of recurrent urinary tract infections, presence of “foreign” bacteria in the vaginal microbiota... Donors must also abstain from sexual intercourse within at least 30 days before sampling and they cannot receive any hormonal treatment. The proportion of eligible women was thus reduced to 35%, a number that should be even lower under real conditions. Moreover, potential recipients should not be exempted from STI screening, not as an exclusion criterium, but to make sure they receive the safest possible post-transplant follow-up.

How can we fight against the transmission of pathogens highly resistant to antibiotics such as vancomycin-resistant Enterococcus faecium (VRE)in healthcare facilities? A promising approach is based on the reinforcement of the gut resistance to colonization through the administration of protective gut bacteria. In mice, bacterial transplant seems to restore the resistance to colonization and reduce the gut density of VRE. This was achieved via the combination called “CBBP_SCSK” of 4 bacterial strains, including Blautia producta (BP_SCSK; where SCSK designates the Blautia strain). However, the underlying mechanisms at play still had to be elucidated. This was partially accomplished by the works recently published in Nature by American researchers.

A lantibiotic similar to E234 preservative

Based on experimental results, BP_SCSK could help reduce the growth of VRE by secreting a lantibiotic (sidenote: Lantibiotic  Low molecular weight bacterial peptide with antimicrobial activity produced by a large number of Gram-positive bacteria ) , similar to nisin A, which is produced by Lactococcus lactis and largely used in the food industry as preservative (E234). Similar...but way more effective and selective.

More effective and selective in vivo

Although VRE growth is inhibited both by BP_SCSK and L. lactis in vitro, things are very different in vivo: only BP_SCSK is detected in the colon (where it represents about 25% of bacteria present 5 days after the administration of CBBP_SCSK); it reduces the density of VRE and inhibits Gram+ pathogens while preserving other gut commensal bacteria. On the contrary, L. lactis is not able to colonize the gastrointestinal tract and has a wider spectrum of action, at the expense of some beneficial bacteria.

A potential probiotic agent

The results also emphasize that genes encoding for the synthesis of lantibiotics are naturally present in human microbiomes from healthy individuals; and that lantibiotic-producing species inhibit VRE. Moreover, in 22 patients with a high risk of contracting VRE infection (because they were undergoing a hematopoietic cell transplant), a high abundance of lantibiotic-coding genes was associated to a reduced density of E. faecium. Similarly, in germ-free mice transplanted with fecal preparations from these patients, the resistance to colonization by VRE is correlated to the abundance of the lantibiotic gene. This supports the idea that lantibiotic-producing gut bacteria reduce the colonization by VRE and are potential probiotic agents that could restore resistance towards this pathogen.

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.”