• Faecal microbiota transplantation is effective in IBS, but a super-donor is essential
• Plant-based foods and Mediterranean diet associated with increased production of SCFAs
• Half of all commonly used drugs profoundly affecting the gut microbiome

Interesting results on the effectiveness of FMT in IBS and on the effects of diet and drugs on the gut microbiota composition and functionality were presented at the UEG 2019 meeting, which just ended. Great interest was shown for the clinical implications of this research.

Faecal microbiota transplantation is effective in IBS, but having a ‘super-donor’ is essential

The results of a large, randomised, double-blind, placebo-controlled trial have confirmed that faecal microbiota transplantation (FMT) using a single ‘super-donor’ is an effective and well tolerated treatment for irritable bowel syndrome (IBS), producing high rates of clinical response and marked symptom improvements.

The study, which involved a large cohort of patients with various subtypes of IBS, used several enhanced methodologies, and highlighted the importance of donor selection for optimising the effectiveness of FMT as a treatment for IBS.

Speaking at UEG Week Barcelona 2019, lead investigator, Professor Magdy El-Salhy from Haukeland University Hospital in Bergen, Norway, explained: «Microbiota dysbiosis is thought to play an important role in the pathophysiology of IBS. However, previous studies investigating FMT in this condition have produced conflicting results. We set out to optimise our chances of treatment success by selecting a single, well- defined, donor who fulfilled European guidelines for FMT donors, and who had a favourable faecal microbial profile».

The ‘super-donor’ was an athletic Caucasian male aged 36 years. He was a healthy, non- smoker, with a normal BMI, who trained five times per week. He had been born via vaginal delivery and breast fed; he was not taking any regular medications, had only received three courses of antibiotics during his lifetime, and regularly took dietary supplements rich in proteins, vitamins, fibre, and minerals.

The study randomized 164 individuals with IBS and moderate-to-severe IBS symptoms (Irritable Bowel Syndrome Severity Scoring System [IBS-SSS] ≥175) to receive either placebo (a solution containing their own faeces), a 30 g donor transplant solution, or a 60 g transplant solution. Unlike in previous studies, the transplant material had been stored frozen (–80 °C/–112 °F), and was administered after thawing into the proximal duodenum via gastroscope – obviating the need for bowel preparation prior to transplantation and making it easier to perform in clinical practice. The primary efficacy endpoint of the study was the percentage of patients who achieved a ≥50-point reduction in IBS-SSS at 3 months after FMT (response to treatment).

According to El-Salhy, a response to FMT treatment was observed in 23.6% of individuals who received placebo, 76.9% of individuals who received a 30 g transplant, and 89.1% of individuals who received a 60 g transplant. Clinically significant symptom improvement [a ≥175-point reduction in IBS-SSS] occurred in 5.5%, 35.2%, and 47.3% of individuals in the placebo, FMT 30 g and FMT 60 g treatment groups, respectively. Significant improvements in fatigue (Fatigue Assessment Scale) and quality of life (IBS- Quality of Life instrument) were also observed in the FMT treatment groups compared with the placebo group. An analysis of faecal bacterial profiles showed changes in the abundance of different bacteria in the two FMT groups, but not in the control group.

«Adverse events after FMT occurred in about 20% of patients and were mild and self- limiting gastrointestinal symptoms such as abdominal pain, diarrhoea or constipation» said El-Salhy. «These occurred intermittently in the first 2 days following FMT».

This study confirms that FMT is an effective treatment for IBS, but stresses the importance of using a super-donor to achieve treatment success.

Plant-based foods and Mediterranean diet associated with increased production of SCFAs

A second study presented at UEG Week 2019 has shown that specific foods could provide protection for the gut, by helping bacteria with anti-inflammatory properties to thrive.

Researchers from the University Medical Center Groningen, The Netherlands, have found that legumes, bread, fish, nuts and wine are associated with high levels of gut bacteria that aids the biosynthesis of essential nutrients and the production of short-chain fatty acids (SCFAs), the main source of energy for cells lining the colon.

The findings support the idea that diet could be an effective management strategy for intestinal diseases, through the modulation of gut bacteria.

The experts observed four study groups, the general population, patients with Crohn’s disease, ulcerative colitis and those with irritable bowel syndrome (IBS). The researchers analysed a stool sample provided by each participant to reconstruct the host’s microbiota and compared this with the results of a food frequency survey. The results identified 61 individual food items associated with microbial populations and 49 correlations between food patterns and microbial groups.

In conclusion, the experts found that:

  • Dietary patterns rich in bread, legumes, fish and nuts, were associated with a decrease in potentially harmful, aerobic bacteria. Higher consumption of these foods was also associated with lower levels of inflammatory markers in stool that are known to rise during intestinal inflammation
  • A higher intake of meat, fastf oods or refined sugar was associated with a decrease in beneficial bacterial functions and an increase in inflammatory markers
  • Red wine, legumes, vegetables, fruit, cereals, fish and nuts were associated with a higher abundance of bacteria with anti-inflammatory functions
  • Plant-based diets were found to be associated with high levels of bacterial SCFA production, the main source of energy for cells lining the colon
  • Plant protein was found to help the biosynthesis of vitamins and amino acids as well as the breaking down of sugar alcohols and ammonium excretion
  • Animal-derived and plant-derived protein showed opposite associations on the gut microbiota

Half of all commonly used drugs profoundly affecting the gut microbiome

A third study presented at UEG Week 2019 has found that 18 commonly used drug categories extensively affect the taxonomic structure and metabolic potential of the gut microbiome. Eight different categories of drugs were also found to increase antimicrobial resistance mechanisms in the study participants.

Researchers at the University Medical Center Groningen and the Maastricht University Medical Center looked at 41 commonly used drug categories and assessed 1883 faecal samples from a population-based cohort, patients with IBD and patients with IBS intermixed with healthy controls. The researchers compared the taxonomic and metabolic functions profiles of drug users to non-drug users, looking at the effect of single medication use and then combined medication use.

The changes observed could increase the risk of intestinal infections, obesity and other serious conditions and disorders linked to the gut microbiome.

Gut microbiota is the microbe population living in the intestine. It contains tens of trillions of microorganisms, including at least 1000 different species of known bacteria. The human gut microbiota population is influenced by a number of different factors, including medications. The microbiome has received increasing attention over the last 15 years with numerous studies reporting changes in the gut microbiota during not only obesity, diabetes, and liver diseases but also cancer and neurodegenerative diseases.

The drug categories with the biggest impact on the microbiome are:

  • Proton pump inhibitors (PPIs) – used to treat dyspepsia which affects between 11% and 24% of the European population. PPIs are also used to treat peptic ulcer, H. Pylori eradication, Gastro reflux and Barrett’s oesophagus.
  • Metformin – used as a treatment for Type 2 diabetes, affecting 10% of European adults
  • Antibiotics – used to treat bacterial infections, taken by 34% of the European population each year
  • Laxatives – used to treat and prevent constipation, affecting 17% of European adults

The gut microbiota of PPI users showed increased abundance of upper gastrointestinal tract bacteria and increased fatty acid production, while metformin users had higher levels of the potentially harmful bacteria Escherichia coli (E. coli).

The researchers also found that an additional seven drug categories were associated with significant changes in the gut microbiota. The use of certain antidepressants (called SSRIs) by those with IBS was associated with an abundance of the potentially harmful bacteria species Eubacterium ramulus. The use of oral steroids was associated with high levels of methanogenic bacteria which has been associated with obesity and an increase in BMI.

Commenting, lead-researcher Arnau Vich Vila said: «We already know that the efficiency and the toxicity of certain drugs are influenced by the bacterial composition of the gastrointestinal tract and that the gut microbiota has been related to multiple health conditions; therefore, it is crucial to understand which are the consequences of medication use in the gut microbiome. Our work highlights the importance of considering the role of the gut microbiota when designing treatments and also points to new hypotheses that could explain certain side-effects associated with medication use».