Focus on the 2018 GMFH

Antibiotics and gut microbiota

The congress began with a Biocodex symposium on the impact of antibiotics on the gut microbiota. Dr. L. Armand- Lefevre recalled that antibiotics cause major alterations in the microbiota, in particular due to both the broad spectrum of antibiotics as well as high intestinal concentrations. In addition, microbiota resilience following antibiotic therapy may be slow and incomplete. In addition to the well-known short-term side effects, such as diarrhoea, taking antibiotics in early childhood is associated with an increased risk of obesity, allergies, and autoimmune diseases, as specified by Dr. A. Mosca.

How can these risks be reduced?

Firstly, by trying to prescribe fewer antibiotics in a better way, moreover, if antibiotic prescription is necessary, by combining them with a probiotic. This is particularly the case for the probiotic, Saccharomyces boulardii, which limits dysbiosis and facilitates microbiota resilience following the discontinuation of antibiotics. Pr. C. Kelly has also shown that S. boulardii decreases the level of primary bile acids and increases that of secondary bile acids, thus reducing the risk of Clostridium difficile infection.

Our mucus needs fibre to defend us

Our fibre consumption has decreased over recent decades, at least in the West, from more than 150 g per day a few generations ago to a dozen grams per day nowadays. This directly impacts the composition of our intestinal mucus. Pr. M. Desai’s Luxembourg team has shown, using a mouse model, that a low-fibre diet results in the intestinal mucus being more strongly degraded by the microbiota via glycoproteins contained in the mucus as an energy substrate. The resulting degraded mucus no longer plays its role against pathogenic bacteria such as Citrobacter rodentium, resulting in lethal colitis in these mice [1].

New biomarkers in colorectal cancer

The potential role of the microbiota in colorectal carcinogenesis is well known. In a metagenomic study conducted in collaboration with Pr. J. Wang’s team in China, Dr. M. Arumugam demonstrated the existence of a“microbial signature” of colorectal cancer (CRC), based on the identification of four biomarkers which were significantly expressed in CRC patients compared to healthy subjects, in geographically different populations (China, Denmark, France, Austria). Of these biomarkers, two bacterial genes of Fusobacterium nucleatum (Fn) and Parvimonas Micra (Pm) were significantly over-expressed in cases of CRC [2]. Another recent study has confirmed the role of Fn as a biomarker of CRC, which significantly increased the sensitivity of immunological screening and made it possible to retrieve 75% of CRC cases which were negative on immunological testing [3].

With this advance in the recognition of a “microbial signature” of CRC, it may be possible to screen asymptomatic individuals for CRC in the near future based on an immunological test for blood in the stools coupled with microbiota analysis.

Impact of the microbiota on the response to immunotherapy

It has been known for a few years that the gut microbiota has an impact on the efficacy of chemotherapies. Recently, studies have also shown that the microbiota plays a major role in the response to immunotherapy. Based on a study of 26 metastatic melanoma patients, Pr. F. Carbonnel’s team showed that the type of microbiota is correlated with the response to ipilimumab (anti-CTLA-4). Patients with a microbiota rich in Faecalibacterium and other Firmicutes demonstrated a high response rate to ipilimumab and a significantly increased survival rate. The occurrence of ipilimumab-induced colitis was also more common in this group [4]. Similarly, another recent study based on 112 metastatic melanoma patients has shown that their responses to anti-PD-1 varied, and their microbiota, alpha-diversity, and relative abundance in Ruminococcaceae (a family whose main member is Faecalibacterium) were the main predictive factors for response [5].

Focusing on faecal microbiota transplantation

As was the case last year, faecal microbiota transplantation (FMT) was the subject of a workshop and was often referred to in the various presentations. Drs. G. Ianiro and Z. Kassam recalled the very promising results of FMT for ulcerative colitis (two positive randomised controlled trials and one trial which showed a positive trend with FMT although significance was not reached), metabolic syndrome, hepatic encephalopathy, irritable bowel syndrome, and digestive GVH (graft-versus-host) allograft. Apart from recurrent Clostridium difficile infection, repeated FMT appears to be essential for “engraftment” and treatment efficacy. Administration in capsules seems to be the future for this technique but questions remain, in particular around intake dose and frequency, since these parameters are also likely to vary according to indication. Access to FMT is increasingly facilitated by the emergence of “stool banks”, in particular, in countries in which microbiota transplants have been assigned the status of organ/tissue rather than medicine. For example, in the United States, 98% of the population is within a two-hour drive of a centre practicing FMT. Thus, this practice has been widely used in recent years, but remains to be standardised and possibly adapted to patients according to their disease and microbiota.

Akkermansia Muciniphila: a new-generation probiotic?

Discovered in 2004, A. muciniphila is a bacterium that prevails in the mucus. It degrades mucin, stimulates butyrate production, and produces a pili-like protein, Amuc1100, that appears to play an important role in the immune response and barrier function of the intestinal mucus. It appears to have beneficial properties since its presence is inversely correlated to obesity, metabolic syndrome, and some cardiovascular diseases [6, 7]. In mice, its administration has beneficial effects on metabolic syndrome, and the first clinical data in humans should soon be available.