Medical research on the impact of antibiotics is hindered by the fact that the studies are generally carried out on polymedicated sick and hospitalized patients. As such, various confounding factors (infection, medications, hospital environment, potential immunosuppression) skew the observations.

The only solution is to conduct prospective studies on healthy outpatient adults, such as this one. American researchers measured the impact of four antibiotic treatments, namely azithromycin (AZM), levofloxacin (LVX), cefpodoxime (CPD) or a combination of CPD and AZM), on the gut microbiota of 20 healthy volunteers randomized into four groups by collecting their stools before, during and two months after the end of treatment (15 collection points in all).

Antibiotic-induced gut dysbiosis 

First finding: antibiotics reduce bacterial abundance and diversity. Depending on the treatment received, changes in abundance differed :

• higher levels of both Bacteroidetes and Clostridium for patients receiving CPD or CPD + AZM at Day 6,
• higher levels of Firmicutes, such as Eubacterium, Ruminococcus and Anaerostipes, for those receiving LVX or AZM.

In addition, AZM (alone or in combination), which has a long half-life, delays the recovery of bacterial abundance, eight bacterial species and some associated metabolic pathways compared to other antibiotics.

A reservoir of resistance genes

Another effect of the antibiotics was the emergence of a long-lasting reservoir of resistance genes in volunteers receiving CPD, AZM and CPD+ AZM treatments, in contrast to those receiving LVX. However, more importantly, the altered composition of their resistome would lead to an increase in three genes (tetO, cfxA, and tet40), two of which do not confer resistance to the antibiotics administered.

Consequently, antibiotic disruption appears to create opportunities for bacteria with broad resistance. For example, Bacteroides that survive CPD treatment, probably via ß-lactam resistance gene cfxA, would create a low-diversity, high-Bacteroides environment, favourable to pathogens such as Enterobacter. Short courses of antibiotics could trigger the acquisition or entrenchment of diverse resistance genes.

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Irritable Bowel Syndrome is a functional gastrointestinal disorder which has depression as one of its most common psychiatric comorbidities. A multi-omic study has recently highlighted the role of the gut microbiota and its metabolites in IBS and associated depression. 

This study³ involved 431 patients from two cohorts:

• one discovery cohort (n=330 patients, 264 with IBS and 66 controls)
• and one validation cohort (n=101 patients, 86 with IBS and 15 controls).

Metagenomic and metabolomic analyses were conducted on stool and serum samples to identify potential biomarkers of the disease.

Serum metabolites as potential IBS markers

Stool analysis revealed only moderate dysbiosis. It appears neither fecal microbiota composition nor fecal metabolites can discriminate IBS patients from healthy individuals. 

However, serum metabolites identified in patients showed significant differences, with greater power to distinguish IBS patients from healthy controls. In total, 726 serum metabolites were identified (compared with only 8 fecal metabolites), including a cluster of fatty acyl-CoAs (a type of fatty acid) enriched in IBS.

_{^{Sources (sidenote: Black CJ, Ford AC. Global burden of irritable bowel syndrome: trends, predictions and risk factors. Nat Rev Gastroenterol Hepatol 2020; 17: 473-86. )}}

Gut bacteria strongly associated with fecal metabolites

Numerous associations (522) between fecal metabolites and gut bacteria were also found. In particular, three species (Odoribacter splanchnicus, Escherichia coli, and Ruminococcus gnavus) were strongly associated with a low abundance of dihydropteroic acid, an intermediate product for folic acid, itself present in very low amounts in IBS patients. Furthermore, among the most significant serum markers in IBS patients were fatty acyl-CoAs, suggesting a deregulation of fatty acid metabolism in IBS.

Deregulated tryptophan/serotonin metabolism correlates with severity of depression 

The results suggest a correlation between tryptophan/serotonin metabolism and the severity of depression associated to IBS. Certain bacteria strains, such as Clostridium nexile or Roseburia inulinivorans, are over-represented in IBS patients with depression and are associated with the presence of certain tryptophan metabolites in serum. The L-tryptophan synthesis pathway is also strongly associated with the severity of depression.

Common and recurrent. This is the profile of urinary tract infections, which tend to affect the same women, 20% to 30% of whom see the infection return up to six times, or even more, per year. Since the gut acts as a reservoir of pathogenic bacteria that travel up the vulva, researchers have been interested in the potential existence of a “gut-bladder” axis, whereby gut dysbiosis is linked to susceptibility to recurrent urinary tract infections (rUTIs).For women suffering from rUTIs is there a specific dynamic in, and between, the gut and bladder? Are microbiota-mediated immunological differences linked to this susceptibility?

To answer this question, a one-year longitudinal clinical study was conducted on 15 women with a history of rUTIs and 16 healthy women. 

Gut dysbiosis and inflammation

The results showed that women with a history of rUTIs had a less diverse gut microbiota, with more Bacteroidetes, and fewer Firmicutes and butyrate-producing bacteria such as Blautia, which are known to regulate inflammation. In fact, blood tests indicate that women susceptible to infection present characteristics of low-grade inflammation. This suggests that susceptibility to rUTIs is partly mediated by a gut-bladder axis, via gut dysbiosis and altered systemic immunity.

The role of E. coli

24 urinary tract infections were reported during the study, all in the rUTI group, and in 82% of the cases, they were caused by E. coli.
However, the dysbiosis observed in the rUTI women did not seem to affect the dynamics of this bacterium: the E. coli populations in the gut and bladder were comparable between the two groups, both in terms of relative abundance and phylogroups. However, no symptoms of urinary tract infection occurred in the healthy controls, suggesting that they alone manage to eliminate E. coli from their bladders. Another finding was that the E. coli strains that cause UTIs often colonize the gut persistently, without being permanently eliminated by repeated exposure to antibiotics. In other words, antibiotics may cure UTIs in the short term by eliminating E. coli from the bladder, but would not protect against recurrences over the long term caused by residual E. coli in the gut.

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BMI 22.45

Prostate cancer is the second most common cancer in men and the fifth deadliest cancer in the world with more than 375,000 deaths in 2020². Despite these figures, prostate cancer is characterized by a very heterogeneous course (in the United States, the 5-year survival rate is estimated at 90%¹).
Today, it is the aggressiveness of the tumor that primarily guides treatment decisions. It is assessed inter alia by the Gleason histopathological score after biopsy, which is an invasive procedure. The identification of urinary markers, which, in combination with clinical data, allows the detection of aggressive forms of the disease, is therefore generating great interest among clinicians.

The urinary microbiota analyzed by molecular imaging and genomics

Studies had already revealed a link between prostate cancer and a specific urinary microbial profile, but also differences in the prostatic bacterial community according to the Gleason score. English researchers therefore turned to the prostate and urinary microbiome, still incompletely characterized, to explore its prognostic potential¹. Using tools such as fluorescence microscopy, anaerobic bacterial culture and genomic sequencing, they analyzed samples of urine and of prostate tissue secretions collected from more than 600 individuals examined in hospital for suspected prostate cancer or hematuria. The subjects were divided into clinical groups and patients diagnosed with prostate cancer stratified according to the D'Amico score.

Anaerobic bacteria linked to tumor progression 

Researchers have demonstrated a significant link between the presence of bacteria in urine and an increased risk of prostate cancer. They also discovered four new bacterial species in the urine samples, the prostatic secretions and the tissues, belonging to the phyla Firmicutes (Fenollariasp. nov. and Peptoniphilus sp.nov), Actinobacteria (Varibaculum sp.nov) and Bacteroidetes (Porphyromonas sp.nov). Five anaerobic species, including three of these new bacteria, were associated with a 2.6-fold increased risk of adverse disease progression, and could serve as potential prognostic biomarkers.

A prognostic, even therapeutic, potential which encourages continued research

The researchers arrived at a hypothesis: these anaerobic bacteria may act on certain metabolic processes.
Such as the conversion of cholesterol into androstenedione, a precursor of testosterone which stimulates tumor growth, or the degradation of citrate, a known marker of prostate cancer aggressiveness. But a causal link between the overrepresentation of these bacteria in patients and disease progression cannot be established at this stage. New research must therefore be undertaken in this respect: if this link is confirmed, a prognostic urine test that is very practical for clinics could be developed. More importantly, targeted antibiotic treatments could control, or even prevent, disease progression.

It stings, burns, warms the cheeks, titillates the taste buds and even the stomach: but it’s good for your health. Anti-inflammatory, anti-cholesterol, anti-hypertensive, anti-obesity... The virtues of chili peppers seem endless.
These beneficial properties are put down to capsaicin, the compound in red pepper that sets the mouth on fire. Although the spicy effect is hard to miss in terms of taste, the mechanisms involved remain unclear. According to one hypothesis, the consumption of capsaicin may enrich the gut microbiota in bacteria that produce short-chain fatty acids (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) , which may be the source of these multiple benefits. 

In vitro study on stool samples

A Chinese-American team carried out an in vitro study to test this hypothesis while avoiding possible interactions between capsaicin and other components of the human body. The researchers collected stool from two healthy individuals, introduced it into a bioreactor mimicking conditions in the colon, and then added either capsaicin or a control solution. After two weeks, the researchers analyzed the composition of the various samples and compared the results with those obtained at the beginning of the study, before the addition of capsaicin or the control solution.

Capsaicin creates a beneficial dysbiosis

Bacterial diversity –which is a sign of good health– increased significantly during the study in the two capsaicin-treated gut microbiota samples, confirming data observed in vivo in various human and mouse studies. The production of some short-chain fatty acids was also altered, but distinctly from one sample to the other: both produced more propenoic acid (known for its role in appetite regulation), but only the first produced more butanoic acid (i.e. butyric acid, which has known anti-inflammatory properties).

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