Colorectal disorders caused by chronic spinal cord injuries may have a significant impact on the quality of life of many paraplegic and quadriplegic patients. Disruptions of the autonomous nervous system can lead to gastrointestinal disorders (discomfort, bloating, flatulence), to a combination of chronic constipation and fecal incontinence, and require laxatives or techniques that encourage bowel movements with or without assistance. In some patients, disruptions are so severe that the wish to improve this neurological gastrointestinal disorder exceeds that of treating urinary incontinence or sexual dysfunctions, or even the loss of walking ability.

Disability-associated bacterial profiles

A Chinese team analyzed the stools of 43 men with chronic traumatic spinal cord injuries (23 paraplegic and 20 tetraplegic) and 23 healthy men. The gut microbiota of disabled subjects was different from that of control subjects. It was less diversified and contained higher levels of Bacteroides, Blautia, Lachnoclostridium and Escherichia-Shigella, among others. Moreover, changes were observed in the bacterial profiles of paraplegic (overabundance of Acidaminococcaceae, Blautia, Porphyromonadaceae, and Lachnoclostridium) and tetraplegic patients (overabundance of Bacteroidaceae and Bacteroide) compared to control subjects. Reduced levels of Alistipes also seem to be associated to longer defecation times in tetraplegic patients.

Blood lipid and glucose levels are impacted

To complete their observations, researchers studied correlations between these changes in bacterial populations and some environmental factors such as age, BMI, and various serum markers (CRP, glucose, liver enzymes, blood lipids, uremia and uric acid, creatinine, etc.). Bacteria from the Bacteroides genus, which are more abundant in tetraplegic patients, were associated with low levels of HDL, probably because of the lack of physical activity. On the contrary, bacteria from the Dialister genus, which are more abundant in healthy subjects, were negatively correlated to blood lipids (LDL, triglycerides and total cholesterol). High blood concentrations of these factors could thus be a sign of worsening colorectal disorders. Megamonas were associated with lower glycemia but also with longer defecation time and increased bloating, probably due to the fermentation of undigested carbohydrates by these same bacteria in the colon. A low level of Prevotella was also related to lower glycemia (thus to a beneficial role), even if other studies have shown pro-inflammatory effects. These results need to be completed by other analytical tools (more detailed analysis of bacterial communities, serotonin assay), by including women in cohorts, and by studying the impact of immobility itself, which may also generate dysbioses.

Cheddar, Stilton, blue cheese or camembert … To prevent the onset of food and skin allergies, children’s diet should include significant portions of cheese, and from the youngest age. That is what a study directed by the National Institute for Agronomic Research (INRA) and Besançon Teaching Hospital suggested. For the first time, it establishes a link between early consumption of cheese and decreased risk of childhood allergic diseases. This conclusion was published in the scientific journal Allergy and was undoubtedly received with jubilation in France.

Diversifying the types of cheese

About a thousand children living in the countryside in five different European countries were monitored since their birth, and their parents reported the eating habits of the family, their lifestyle and the health condition of the young participants. Results: the children who ate cheese regularly and/or in large amounts from the age of 18 months, developed less food allergies and eczema (atopic dermatitis) than the others throughout the first six years of life. The more varied the cheese, the more benefits there seems to be. Nevertheless, the study did not reveal any protective effect against allergic rhinitis or asthma.

Richer microbiota

The researchers assume that this protective effect is related to the different microorganisms (bacteria, yeasts and molds) present in cheese. This microbial diversity seems to positively impact the composition of the human gut microbiota in addition to a varied and balanced diet during the first year of life (vegetables, fruits, yaourts, raw milk…). The researchers indicated that “thanks to its rich microbial composition, cheese could change the gut flora and promote its diversification” and reminded us that many studies have already shown that a disrupted or depleted microbiota provides a breeding ground for allergies. To better understand the impact of cheese on the microbiota, the scientists intend to closely analyze the gut flora of cheese lovers.

Sources:

Nicklaus S, Divaret‐Chauveau A, Chardon ML et al. Pasture Study Group. The protective effect of cheese consumption at 18 months on allergic diseases in the first 6 years. Allergy. 2019 Apr;74(4):788-798

Research on colorectal cancer (CRC) is mainly focused on bacterial populations but is gradually widening to include other microorganisms (fungi and viruses). A study carried out by a team from Hong-Kong focused on the specificities of the mycobiome in patients with colorectal cancer. Stool analysis from 73 patients and 92 healthy volunteers revealed a fungal signature in patients with CRC: the Basidiomycota:Ascomycota ratio is increased (the two most abundant phyla in the human mycobiome), although fungal abundance and diversity remain unchanged.

Opportunistic and protective yeasts

More specifically, 6 fungal genera were more abundant in the stools of patients with CRC, and among them, some opportunistic pathogens such as Acremonium (Ascomycota) and Rhodotorula (Basidiomycota). The same was observed for Malassezia yeast (Basidiomycota), which is usually found in the skin and is involved in atopic dermatitis, among other diseases. It could thus be able to colonize the intestines though a mechanism similar to the one used by Candida albicans (Ascomycota). Some species of Aspergillus were also more abundant in patients with CRC, especially A. flavus which produces aflatoxin and is potentially carcinogenic. On the contrary, the levels of Saccharomyces cerevisiae yeast, known to colonize the gut microbiota and to have other anti-inflammatory and regulative properties of the immune system, were decreased in patients with CRC. According to the authors, this could constitute a potential therapeutic approach. These fungal dysbioses were validated by the same team in two other cohorts and could be used as diagnostic biomarkers.

An indirect role for bacteriophages?

In another study, North-American researchers analyzed the stools of 30 patients with carcinoma, 30 patients with adenoma and 30 healthy subjects. They observed that viral diversity and abundance were not altered in patients with carcinoma / adenoma, and shed light on the role of certain bacteriophages (from the Siphoviridae and Myoviridae families, among others) in colorectal carcinogenesis. According to scientists, some bacteriophages could disrupt colon bacterial populations and be associated to tumor progression. By promoting bacterial lysis, they could allow opportunistic species anchored to the epithelium to produce a biofilm favoring the penetration into the intestinal lumen of oncogenic bacteria which trigger the inflammatory immune response. Unless… bacteria are the one to impact the virome, and not the opposite? A lot of hypotheses have been proposed and several elements still need to be clarified in order to extend the diagnostic and therapeutic arsenal and fight the third most commonly diagnosed cancer in the world in 2018.

Gluten is a major component in wheat, barley and rye, and consists of proteins that are mostly insoluble and difficult to digest. They then accumulate in the intestines where they can interact with the immune system, disrupt gut permeability and change the microbiota’s activity. Only a true gluten intolerance, called celiac disease, requires a permanent gluten-free diet.

Low-gluten vs. high-gluten diet

Given the popularity of gluten-free diet with the general population, researchers carried out a study in 60 healthy adults, comparing a low-gluten diet to a high-gluten diet (respectively 2 and 18 g per day). Both diets lasted eight weeks and were separated by a period of at least six weeks when participants resumed their regular diet (12 g of gluten per day). In both groups, dietary intake was the same (number of calories and nutrients, amount of fiber) and the only difference between the two diets was the nature of ingested fibers.

Benefits with unexpected causes

The results indicate that a gluten-free diet changed the composition of the gut microbiota (significant decrease in bifidobacteria), and that it mainly modulated its activity. The participants reported improved gastrointestinal comfort and less bloating, as well as a slight weight loss. A very small drop in inflammation was also observed, indicating an impact on the immune system. Are these results in favor of a low-gluten diet? Not so sure… These benefits seem to be related to the larger diversity of ingested fibers rather than to the decreased consumption of this protein. By excluding products containing gluten, people are forced to eat different sources of fiber such as vegetables, rice, corn or quinoa. According to researchers, the composition of these fibers, and not the lack of gluten, is the reason why there is a positive impact on the microbiota. The researchers indicated that there is no need to encourage people to follow a gluten-free diet, but they have everything to gain by diversifying their diet, as usually recommended by nutritionists…

19.1% of deliveries worldwide are performed by C-section. This number rises to 25% in Europe and raises ethical questions since this delivery mode is frequently carried out for comfort rather than for medical reasons. We already know that the mode of delivery affects the composition of the gut microbiota in newborns, mainly through the potential contact with the vaginal, skin (and sometimes fecal) flora of the mother and through the use of antibiotics in case of C-section. Since the first days postpartum are a critical time window for the development of the neonatal immune system, an international team focused on the type of intestinal bacteria transmitted from mother to child according to the type of delivery. The team completed their analysis by studying bacterial genes and assessing their functions.

Vaginal delivery: stimulation of the LPS biosynthesis pathway

In this study performed on 33 newborns, the main finding was that children born vaginally had an overabundance of gram-negative bacteria (Bacteroides and Parabacteroides) that seemed to strengthen physiological functions. On the other hand, caesarean delivery promotes the contact of newborns with the mother’s cutaneous microorganisms and the transmission of Staphylococcus, which is found in higher levels in the stool of newborns born this way. Researchers explained that the abundance of this type of bacteria in newborns born vaginally could be related to an increased stimulation of the lipopolysaccharide (LPS) biosynthesis pathway (LPS are components of the external membrane of gram-negative bacteria), compared to newborns born by C-section. These LPS are endotoxins and promote the production of pro-inflammatory cytokines (TNF-a and IL-18) in plasma. These cytokines are found in higher levels in newborns born vaginally.

Immunostimulant potential confirmed in vitro

The extraction of LPS from the stools of newborns born vaginally or via C-section in order to stimulate in vitro primary human immune cells confirmed that C-section delivery is associated with lower production of TNF-a and IL-18. This confirms the lower immunostimulant potential of the gut microbiota of caesarean-born children who were not exposed to the mother’s vaginal bacteria, as well as the limited vertical transmission of some bacterial strains to newborns. This factor could have lifetime impacts in terms of increased risk of developing inflammatory, immune, metabolic disorders, and even chronic diseases. Nevertheless, these results need to be confirmed in larger cohorts with longer term follow-ups in order to better understand the effect of early microbial exposition on innate and adaptative immune responses.

We know that body odor is mainly due to the bacterial decomposition of natural constituents of sweat, which is produced by sweat glands. But we do not know which species are involved and what mechanisms come at play among young people. The researchers thus enrolled prepubescent children (5-9 years old) and teenagers (15-18 years old) and analyzed sweat samples from armpits, neck and scalp, each time 1 hour after a shower, following physical activity, and 7 hours later.

Each species has its own smell

At all times, teenagers had a stronger body odor than children, especially in the armpits. After physical activity, children’s sweat was characterized by a rather sour smell, while that of teenagers had a dominating sulfur-like odor. On the scalp, whatever the age, a greasy odor was detected. According to the researchers, these differences highlight the heterogeneity of skin microbiota species causing unpleasant odors and above all, the influence of some of them.

What causes these bad smells?

Two species predominate in the neck and scalp: one is more abundant in children, the other in teenagers. This difference reflects the changes in sweat gland activity that occur in puberty. But the main finding is the major role played by staphylococci in the body odor of both children and teenagers–a role that is played by bacteria from the Corynebacterium genus in adults. What about the sulfur-like smell in teenagers’ armpits? It is probably related to the acid production from the Staphylococcus epidermidis bacteria. And the sour smell found in children’s necks? Staphylococcus hominis is to blame.

Deodorants especially designed for teenagers?

According to the scientists, the transition from a rather sour-smelling sweat during childhood to a sulfuric smell during adolescence is the result of the reorganization of species within the skin microbiota that occurs in puberty. This discovery could be useful to the manufacturers of deodorants, since the latter are designed to control bad smells in adults, but not in teenagers.

The latest therapeutic advances in oncology owe much to immune checkpoint inhibitors (ICI), monoclonal antibodies currently targeting CTLA-4 (sidenote: CTLA-4 Cytotoxic T-lymphocyte-associated antigen 4 ) , PD-1 (sidenote: PD-1 programmed cell death protein 1 ) and PD-L1 (sidenote: PD-L1 Programmed cell death ligand 1 ) . They are much less toxic than chemotherapy, but the first marketed treatments are still associated with immune-mediated adverse reactions, especially refractory colitis. The optimal treatment of these types of disorders has yet to be found. An American team studied the potential benefits of fecal microbiota transplant (FMT). Objective: fight against ICI-induced dysbiosis and promote bacterial mechanisms combating local inflammatory processes.

Promising initial results

The analysis of the bacterial populations before the fecal transplant in the two patients revealed the absence of protective bacteria (from the Bacteroidia and Verrucomicrobiae classes). The first patient was a 50-year old woman treated for chemotherapy-resistant metastatic transitional cell carcinoma and hospitalized for ICI-associated ulcerative colitis. Since colitis symptoms were resistant to standard treatments, she was transplanted, via colonoscopy, a unique stool dose from a healthy donor. Result: progressive and fast disappearance (36 days) of colic symptoms, confirmed by endoscopy. The second patient was a 78-year old man treated with ICI for chemotherapy- and hormonotherapy-resistant prostate cancer. After the onset of immunotherapy-associated colitis that was resistant to all standard treatments, he received two stool doses (separated by a 67-day interval) from the same healthy donor. Clinical symptoms were partially reduced by the first transplant and eliminated by the second, as demonstrated by endoscopy.

Post-transplant evolution

The analysis of fecal samples collected throughout the study showed that gut microbiota populations changed following the transplant. Although diversity remained stable, bacterial abundance temporary increased in both patients and the recipient’s microbiota became more similar to that of the donor in the days following the transplant. Immediately after the FMT, recipients were once again colonized by bacteria from the Bifidobacterium and Blautia genera, known for overriding the toxicity of ICI in a murine model and associated with the decrease of gastrointestinal inflammation. These preliminary results still need to be confirmed; they could be a possible response to therapeutic needs that will keep increasing as the use of ICI becomes more common.

It may sound funny, but NASA researchers took this discovery very seriously. In the BMC Microbiology journal, a team from the prestigious aerospace research center explains that the presence of these bacteria could become a hazard to astronauts during long-term missions in space, or even during the first manned space flights to Mars. It would be impossible to turn around during this 260-million-kilometer-long journey and come back to Earth in order to treat infected individuals.

Drug resistant strains…

By studying the DNA of these 5 bacteria, the scientists discovered that they presented strong similarities with 3 enterobacterial strains (present in the intestines) recently isolated on Earth in Tanzania and the US. They are responsible for serious hospital-acquired infections in immunocompromised persons and newborns, and they are part of a bacterial species known for being highly pathogenic and resistant to multiple antibiotics. Additionally, the researchers indicated that the strains found in the international space station were also resistant to many antimicrobial agents (penicillin, for instance) which are “antibiotics used by astronauts for over 20 years”, as underlined by the researchers.

…although harmless so far

Fortunately, these strains were not virulent and did not threaten the astronauts’ health. But they could very probably become pathogenic (79% probability) under specific conditions (to be determined) such as the very low gravity found in the ISS: several studies suggested that this condition may increase bacteria’s virulence and resistance to antibiotics or impact the growth or size of microorganisms. This study also reminds us that the international space station is not sterile: astronauts come on board with their microbes, and other microorganisms may be introduced by food or material shipments sent to the station.

ICU patients are particularly exposed to the risk of gut dysbiosis, which may promote infections by opportunistic bacteria or external pathogens. This could favor the onset of antibiotic resistance in patients often subject to heavy antibiotic therapy. This is particularly true for Pseudomonas aeruginosa, for which it is critical to develop new antibiotics according to the WHO.

Particularly resistant bacteria

P. aeruginosa shows an alarming resistance to carbapenems (estimated at 25% in France and 28% in the US). A North American team focused on the link between gut dysbiosis, antibiotic therapy and colonization by carbapenem-resistant P. aeruginosa (CRPA) in 109 patients admitted in ICU and divided into three groups: a control group who did not receive any antibiotic and did not develop CRPA, and two antibiotic-treated groups (one where patients developed CRPA and one where they did not). Antibiotics used were vancomycin, the standard molecule to fight MRSA (sidenote: MRSA Methicillin-resistant Staphylococcus aureus ) , and a combination of piperacillin and tazobactam with anti-anaerobic and anti-pseudomonal activity.

A path open to pathogens

The combination of piperacillin and tazobactam proved to be detrimental to beneficial bacteria, such as Lactobacillus and Faecalibacterium, used in some probiotics, and Blautia, which could help prevent Clostridium difficile infections. Simultaneously, the treatment favored the growth of opportunistic pathogens such as Enterococcus. Vancomycin was associated to a decrease in Bifidobacterium. Overall, the risk of CRPA emergence was nearly three times higher in patients who had received one of these treatments, compared to those who had not be treated with antibiotics.

Profiling at-risk patients

The researchers also identified some bacteria with a protective role against CRPA: Peptoniphilus, Prevotella and bacteria from the Clostridiales order. They could be used as biomarkers in intensive care patients to adapt antibiotic therapy when the presence of CRPA has been confirmed or when there are signs of infection. However, the authors indicated that some of these protective bacteria like Finegoldia, Anaerococcus and Peptoniphilus have previously been associated to chronic infections and wounds. Prior to any clinical application, research must be continued and include other microbiotas (skin and respiratory) as well as other potential colonization sites.