Tandem 5: Characterizing trade-offs of the human FUT2 gene for the improvement of gut health

Background – The gene FUT2 encodes an α1,2 fucosyltransferase responsible for the expression of ABO histo-blood group antigens on mucosal surfaces and in bodily secretions. Individuals bearing at least one functional allele are known as "secretors", whereas those homozygous for loss-of-function mutations display a "non-secretor" phenotype. The non-secretor phenotype exists in human populations and has been maintained by strong selective pressure over a period of 3 MY. This indicates the existence of strong trade-offs, whereby host-microbe interactions are a likely cause. In particular, non-secretors are resistant to infection with the Norwalk (Noro) virus, but are more susceptible to other infectious and chronic diseases involving microbes, such as inflammatory bowel disease (IBD). The Fut2 gene is important for the assembly of the gut microbiota and its management under stress. Thus, it represents an important genetic factor to consider for the development of microbiome-related interventions, such as probiotics or fecal microbiome transplantation (FMT). Intestinal lactic acid bacteria and Bifidobacteria have been intensely investigated for their utilization as human probiotics. Probiotic microorganisms improve or restore microbial homeostasis by two scenarios: occupation of functional niches (competitive exclusion) or their antagonistic activity. It is well known that the gut microbiota interacts with human health and modulation of the microbiota by probiotics is a potential way to prevent some diseases.

Overall objectives

  • Characterize the reduction of Lactobacillus, which is observed in both non-secreting humans and mice, at the species- and strain level.
  • Evaluate whether local adaptation to FUT2 genotype-dependent environmental differences exists among microbiomes.
  • Explore whether improved understanding of functionally important microbial losses may be exploited for preventative and/or therapeutic purposes.

Doctoral project 5.1: Relationship between Lactobacillus diversity and host FUT2 genotype

Specific aims

  • Define species-level taxonomy of Lactobacillus sp. that differ according to FUT2 genotype in human fecal samples.
  • Evaluate the pan-genome of Lactobacillus species according to FUT2 genotype in humans.
  • Characterize functional genomic content according to FUT2 genotype in humans.

People working on this project

  • PD Dr. Charles Franz
  • MSc Ana Sofia Galrinho Borges

PI's Homepage: https://www.mri.bund.de/de/institute/mikrobiologie-und-biotechnologie/mitarbeiterinnenmitarbeiter/franz-charles/

Doctoral project 5.2: Evaluating the gut microbiome for adaptation to host Fut2 genotype

Specific aims

  • Evaluate ecological and evolutionary changes in the gut microbiome during FMT experiments with wild type and Fut2-deficient donor/recipient mice
  • Determine differences in inflammatory outcome of autologous vs heterologous FMT in wild type and Fut2-deficient mice
  • Evaluate influence of specific Lactobacillus strains on FMT-induced and host genotype-dependent effects on disease

People working on this project

  • Prof. Dr. John Baines
  • MSc Meghna Basu

PI's Homepage: http://web.evolbio.mpg.de/evolgenomics/