Conference Report Gut Day 2019
5th of December 2019 – MiCa Amsterdam 1) Keynote lecture: Clara Belzer – “Nature and Nurture of Our Microbiome.”
This woman centered her talk around the gut microbiota in pregnancy in birth.
- A baby being born is being inoculated by a big number of bacteria from the mother. Depending on the mode of delivery – vaginal or by C-section – the microbiota in the gut of the child will start of mainly from vaginal or skin origin.
- Other factors determining the further development of the baby’s gut microbiota: Breast feeding or Formula feeding– weaning foods and age – use of medication and antibiotics…
- All kinds of techniques through the decades (DGGE, microarrays and sequencing methods) have shown that there are differences in the gut microbiota between breast fed and bottle fed babies and between baby’s born through C-section or vaginal birth.
- Later in life: differences between modes of birth or feeding aren’t vidible anymore, but are visible in functions.
- Children born with caesarian have higher risk of allergies , diabetes and obesity.
- Between 4-6: adult like microbiota
- An anekdote to illustrate the non necessity of the gut microbiota for human life: “Bubble boy” is a boy with a genetically comprised immune system. He was living in a plastic bubble and lived completely sterile. => IS possible.
- However, from work with germ free rats, we know that the physiology of mammals living without bacteria is different, if not comprised. Germ free mice f.i. have a very enlarged caecum.
- The gut microbiota fulfill a number of useful functions: They provide vitamins, digest fibre into SCFA, and provide protection against pathogens.
Back to babies…on the importance of breast feeding
- Human milk and mucus are important nutrients for the gut microbiota of the baby. The gut microbiota produce SCFA from the digestion of these compounds.
- It may be important for a baby to receive as many bacteria from the mother as possible, because the mothers microbes are adapted to her immune system and may be able to digest her own milk sugars better. Passing these bacteria to her baby may improve the digestion of the baby.
- Mothers milk contains fibers: Human Milk Olygosacharides => stimulates Bifidobacteriaceae growth in the intestine of the baby.
- Premature infants are often helped in their breathing by blowing O2 rich air in their surroundings. This practice has been shown to stimulates the growth of aerobes / facultative aerobes in gut.
Some beneficial bacteria, in the context of baby’s.
- Akkermansia muciniphila is a mucin consuming bacterium in the human gur and is connected to healthy status. It is thought to have anti-obesogenic properties and is less abundant in chronically ill individuals.
- It is also known to consume oxygen in the gut environment, aiding the generation of a more anaerobic environment and it’s consumption of human mucus is though to stimulate mucus production.
- Akkermansia is also able to provide a basis for crossfeeding on mucus. When combined with other bacteria that could not feed on mucus, A. muc could “predigest” the mucus after which the other bacteria could ferment the endproducts provided by Akkermansia.
- Akkermansia muciniphila is such a promising organism that Patrice Cani and his team have been working on a human trial with a treatment of Akkermansia. Another team, onder supervision of Willem de Vos, is now working on a product tailored to the broad public.
- MOOC: free online course on microbiota from Clara Belzers group.
- After the presentation, the question was posed if A. muc could really be this magical bacteria that is a cause for health, or is it rather a sort of indication for a healthy condition?
2) Platform presentations morning
a) Gabriela Bravo-Ruiseco: Silicon inclusion in F. prausnitzii : a survival mechanism?
- Aim: study mechanisms that allow F. prausnitzii to survive in the gut.
- This girl has been using microscopy and X-ray spectrometry on F. Prausnitzii and found out that F.
Prausnitzii can contain eye shaped inclusions => it looks like F. Prausnitzii collecting silica.
- Some other bacteria do that too, like B. cereus. Collecting silica may provide protection against acid environment, dehydration and UV-light.
- Further research has to determine the genes for silica-inclusion (CotG in B. Cereus)
- It would also be interesting to investigate wheter this new mechanism is also happening elsewhere, f.i. in wastewater treatment plants.
b) Prokopis Konstanti: Treatment of eosinophilic esophagitis with an elemental diet is associated with changes in the microbial communities of the upper gastrointestival tract.
- This man is researching eosinophylic oesophagitis, an immune disorder of the oesophagus, in relation to the gut microbiome. He studies whether diet treatments can alter the gut microbiota of patients and in this way attenuate the patients immune system.
- In eosinophylic oesophagitis air or food allergens may trigger Th2 inflammatory response. There is currently no cure
- Treatments include taking proton pump inhibitors and using topical steroids - Dietary treatmens: elemenation diets – elemental diets (highest remission rates) - Link with the microbiome? Both allergies and diet are related with microbiome.
- The research comprised an elimination diet as a treatment and the gut microbiota alterations were studied.
- The elemental diet managed to resolve oesophagal inflammation. The gut microbiota of the patients was alto altered by the disease. Amongst others, Veillonellaceae and Streptococcaceae were more abundant in during active disease and were lower after treatment.
- Conclusion: diets can alter the microbiota in GI tract during disease treatment.
c) Marlies Lissans: Inhibiting Salmonella EPS production is evolutionarily robust.
- Salmonella is know foodborne pathogen that can form biofilms, f.i. on gut cancer growhths.
- Biofilms must contain EPS and EPS production is a target for antibacterial agents.
- When combined with EPS non-producing bacteria, EPS producers can be outcompeted, because EPS- production has a cost. EPS non-producers are at an advantage.
- Combining the right EPS non-producer with an EPS-producing Salmonella may thus be a technique for Salmonella repression.
d) Marjolein Klaassen: Anti-Inflammatory gut microbial pathways are decreased during Crohn’s disease exacerbations.
- The gut microbiota is thought to be responsible for disease flare-ups in Crohn’s disease.
- In this study, research was conducted as to how the microbiota of a person with a flare-up is different from a person without one.
- They performed sequencing on fecal material from patients with and without flare-ups
- Results showed no taxonomical difference distinction for people with or without flare-ups. There was, however, a distinction on a functional level: several anti-inflammatory bacterial pathways were decreased.
3) Keynote lecture: Cyriel Ponsioen - “FMT for IBD, is there light at the end of the tunnel?”
Question handled in this presentation: how can FMT be applied for IBD-curance?
- Ge Hong (an ancient chinese wiseman) onxe said: “when you have diarrhea, you should consume faeces of your neighbour”
- This quote –and others – illustrates that the idea of fecal transplants is not new.
- In IBD, the presence of the gut microbiota is crucial. Without it, no IBD occurs, ever. A level of immune system dysfunction is also a factor. In a person with IBD, the immune system overreacts to the gut microbiota.
- A few strategies are currently applied to combat IBD flare-ups.
o Antibiotics: these cannot be used chronically o Probiotics:
o …
- It is known that the functional landscape of the gut microbiota is much more diverse across individuals than the compositional landscape.
- In one of their own studies, Mr. Ponsioen described how FMT was used for UC-curance in human patients. As a result, many of these patients had been ‘cured’, i.e. they have been in remission for years.
So what happened here?
- Well, they discovered that a gene for butyrate production, the butCoA gene was increased in patients that stayed in remission (Fuentes 2017).
- They also related sustained remission to a higher abundance of Clostridium cluster IV and XIVa, versus patients that relapsed.
- This work highlights some taxonomical and funtional indications of dysbiosis happening in UC.
- Mr. Ponsioen also highlighted there are lots more human trials ongoing, so more information will be coming.
- FMT has received some critiques that they may be dangerous and lead to infections of opportunistic pathogens. In truth, Mr. Ponsioen did report some casualties, 1 or 2 people that got pneumonia.
- He also described though, that in the trials he monitors, he does not include people who are on severe anti-inflammatory drugs. This to limit the chance of bacteremia.
- FMT from people that are more different than you may also be more beneficial than from people you have a close relationship with.
4) Platform presentations afternoon.
a) Bastiaan Haak: Transkingdom analysis of the intestinal ecosystem of critically ill patients on the intensive care unit (ICU).
- In critically ill patients, overgrowth of several pathogens is observed, f.i. Staphylococcus, Streptococcus, Lactobacillus, Enterococcus, Klebsiella..)
- Overgrowth of these pathogens increases the risk of nocosomial infections and organ failures.
- Mr. Haak is now researching if alterations in Gut MO in ICU also translate to fungosome, virome (prokaryotic and eukaryotic,…)
- Study setup: look at virome, fungosome and bacteria in feacal bacteria from patients form the ICU.
- He observed, interestingly, that when overgrowth of certain pathogenic bacteria was observed, also their repective bacteriophages were more present.
- Interestingly, when overgrowth of certain pathogenic bacteria, usually also the bacteriophage is more present.
e) Benoit Marsaux: Application of the SHIME platform to assess the interplay between fungi and bacteria in the gut
- 1.6 mio people per year die due to a fungal infection
- Fungal infections are also extremely dangerous: Half of all people that have fungi in the blood die - Candida albicans = one of the fungi that causes problems and also the one Benoit works with for now.
- The gut is the reservoir of most fungi in the body.
- People receiving cancer treatment appeart to be more susceptible to fungal overgrowth.
- Benoit is going to try and study gut fungi in the SHIME-system. Therefore he first needs to try and keep them alive in the SHIME-system.
- At this moment, the SHIME is not yet characterised for fungal presence. Fungi have as of yet not been studied here.
- In Benoit’s first SHIME trial he tried to make Candida albicans prevail in the SHIME. He observed that it grew out in one individual, but was flushed out with the fecal material from another individual.
- He concluded that antibiotic treatment in SHIME may be needed to have the fungus prevail in the SHIME-system.
f) Quinten ducarmon: The bacterial gyt microbiota during controlled human infection with Necator americanus larvae (hookworm)
- Hookworm infections can occur in humans.
- In the western world, these infections aren’t prevalent, but in developping countries in Asia, Africa and Central and South America they still occur.
- Such an infection can lead to iron deficiency aneamia and protein deficiency - The worm lives in the gut where they feed on blood. They penetrate via the skin.
- The question in this study was if this helminth can affect the gut MO.
- Helminths are known to increase mucus secretion
- The described study setup was a study in healthy humans: 3 groups of 6 or 7 individuals. These people were infected with the worms in different doses and fecal samples were collected.
- In this study they observed that in people with high GI symptoms, a more unstable microbial system was found
- They also found strong individual clustering.
g) Matthew davies: Does our microbiome travel well? Microbiome resilience and acquisition of multidrug resistant bacteria in travellers.
- Extended spectrum beta-lactamases (ESBL) can be produced by species like E.coli, Klebsiella spp., etc.
Members of the Enterobacteriaceae family. They use these chemicals to deactivate lactam-based antibiotics, like cefalosporines and penicillines.
- Concern about these ESBL’s was raised, as they can limit the treatment of infections.
- In this study, the taxonomy of the gut microbiota was investigated with regards to the presence or absence of ESBL-producing bacteria.
- The diversity of the gut microbiota was not significantly different between people that did or didn’t produce ESBL’s.
- There were also no taxonomical differences detected.
- Several taxa are significantly linked to ESBL acquisition
h) Gerben Hermes: Why cross-sectional microbiota analysis do not provide consensus observations: a case for the need of temporal data.
- There is still no good consensus on what the IBS-microbiota looks like. This problem may be due to a lack of longitudinal sampling in patients: there may be a big variation in gut microbiota composition in one individual in time.
- In the study described here, the aim was to characterize the gut microbiota of IBS-patients longitudinally. They acquired 155 people, among which 55 patients and took their stool sample every 2 months. They ended up with 504 stool samples.
- The plots shown explain that the gut microbiota fluctuates in composition over time and relation with a specific bacteria isn’t alsways straightforward. The prevalence of certain bacteria in IBS-patients vs controls can even flip around!
- Some bacteria are on one timepoint more availabe in IBS-patients, on another timepoint more in control patients
- Conclusion: snapshot on one timepoint may not be representative for disease state. Repitions in time are more valuable.
5) Keynote speaker: Frederik Bäckhed – “Microbiota in human metabolism: from bench to clinic and back.”
This man talked about some associations that are being made between the gut microbiota and diseases, more particularly diabetes.
- The gut microbiota is ASSOCIATED with a lot of diseases, but the real MECHANISMS are in many cases not known yet and they’re not always easy to study.
- Germ free mice are being used as a model to study causality: whether a disease (symptom) occurs without a microbiota or not. This way it was clear, f.i. that diet plays a crucial role in diet induced obesity.
Germ free mice are resistand to developping diet-induced obesity. Moreover, energy substracted from fiber in the diet was not a confounding factor in these studies, because the study diet were devoid of fiber.
- One of the more common observations is that obese individuals have a gut microbiota with lower alpha- diversity.
- The Wellness study has targeted the variability in the gut microbiota within humans
o They observed a heterogeneity between individuals microbiome variability. The amount of different species within an individual is highly variable, the variation of the gut microbiota of an individual in time is also different from person to person, etc.
o Variation (in time) depends also on which taxon you’re looking at.
- Diabetes is related to alterations in the gut microbiota:
o It is associated with a drop in butyrate producers.
o Diabetes treatment under the form of metformin could also shape the gut MO, but more positively. In this sense, a metformin altered microbiome contributes to improved glucose metabolism.
o An important note is that a diabetic state – like most other diseases – is not an on or off state.
There is a range of symptoms & metabolic parameters that appear on the range from normal to diabetic.
o The question is also raised if the microbiota can be used as a predictor for diabetic status.
- Bariatric surgery is often used as a treatment for obesity and it’s shown to cause some changes in the gut microbiota.
o bariatric surgery was followed by an enrichment in some taxa after a few years and these microbial changes could be conferred through to germfree mice.
o The researchers also investigated if the microbiota lost or gained some butyrate producers.
o Sleeve gastrectomy was followed by better glucose tolerance, could it also have an effect on the microbiota?
- Research has also shown that 4 bacterial metabolites differ between diabetics and non-diabetics (Koh et al 2018). One example is imidazole propionate, which is a histidine metabolite.
- The observed rise in imidazole propionate was not related with histidine intake, but rather enterotype 2, dominated by Bacteroides and with lower diversity.
- Cellular gene pathways are being discovered about the impact of imidazole propionate.
