Ongoing Projects

Coordination of host-microbe interactions by crosstalk with anti-glycan antibodies in inflammatory bowel diseases:

Humans have relatively high levels of natural antibodies (NAbs) recognizing a broad spectrum of glycans. They are classified as “natural” Abs detected without traceable immunisation against the cognate antigen; however, they are potentially generated in response to explicit members of gut microbiota expressing specific glycans. One of the most abundant NAbs is anti-Gal Abs detecting α-gal glycan that accounts for approximately 1-5% of circulating IgM and IgG and are produced by over 1% of the B cell repertoire in adults. The titers of anti-Gal Abs do not substantially change in healthy subjects over time. However, these NAbs are elevated in many disease conditions, including allergies to meat, infectious diseases, immune reactions to biologics such as TNF-α, autoimmune diseases and inflammatory bowel diseases (IBD).

We showed that i) anti-Gal Abs can be induced by manipulating the gut microbiota that ultimately trigger a natural protective response mechanism against malaria transmission [Yilmaz et al., Cell, 2014]; and ii) the gut microbiota of IBD patients are relatively different from healthy subjects, mostly with an increase of enteropathogenic strains due to the luminal presence of reactive oxygen species (ROS) in an altered metabolic niche and reduction of short-chain fatty acid production, a key factor for inhibiting oxidative stress and limiting the induction of DNA damage [Yilmaz et al., Nature Medicine, 2019]. Knowing the potential induction of anti-Gal Abs via manipulating gut microbiota, altered microbiota profile and elevated anti-Gal Abs in IBD patients associated with disease activity compared non-IBD have led me to ask what the role(s) these most abundant NAbs have for maintaining an ongoing mutualistic relationship and how these antibodies contribute to the trajectory of cyclic relapsing and remitting activity and the responsiveness to anti-inflammatory treatment of disease once inflammation has been initiated.  

Evolutionary dynamics of bacteria in the intestines of IBD patients.

An initially mutualistic relationship between the host and its microbiota can lead to alterations in the composition of microbial consortia and their metabolic functions, accompanied by a loss of fitness of the host — this may result in manifest a disease such as in inflammatory bowel disease (IBD). Many studies, including our recently completed paper, show that the gut microbiota of IBD patients are relatively different from non-IBD subjects, mostly with an increase of enteropathogenic strains due disease activity and environmental changes within the gut. This study aims to understand the evolutionary changes in gut microbiota of IBD patients in the presence of fluctuating disease activity in the gut by combining the different meta-omics measurements on microbes and basic state-of-the-art microbiology.  Understanding how the disease activity affects genomic variation in IBD gut microbiota and whether this is beneficial to the aetiopathogenesis of pathobionts in an altered metabolic niche will uncover the molecular biomarkers including particular variants that are relevant to human health and well-being.

Metagenomic Insights into Ancestral Human Microbiota.

Ancient microbiota preserved in paleofeces can be a rich source of information on the evolution and co-occurrences of microbial species. Retrieving the ancestral state of the human gut microbiome information from samples left behind by our distant ancestors would provide an ideal approach to understanding the co-evolution of humans and microbes. Hence, this study will help to identify how ancestral human microbiomes are atypical of modern cosmopolitan populations and will lead to novel paths of exploring the prehistoric human conditions in the context of modern human health. We will characterize the compositional changes in human microbiomes in ancient traditional communities, potentially revealing an important aspect of the ancestral human microbiota compared to modern cultures existing on the very same soils; from fecal material, the typical sample proxy for characterizing distal gut microbiomes obtained from different cultures had lived in the same area over 1500 years; iii) whether there were any dramatic changes in microbial profile when the new cultures arose.

Targeting D-lactate producing gut microbial strains in pediatric IBD patients

(Collaboration with Dr. PD Dr. med. Christiane Sokollik, (http://www.kinderklinik.insel.ch/de/unser-angebot/details/person/detail/christiane-sokollik/). The altered colonic microbiota plays a major role in the production of D-lactate, a problem in IBD subjects due to the presence of high proportion of D-lactate-producing gut bacteria. The severity of the symptoms that negatively influences the daily life of subjects raises the question whether this altered metabolic condition can be corrected with a potential primer restoring microbial balance and modulating mucosal protection. In this study, we aim to test whether i) the altered gut microbial profile supports the relative increase of D-lactate producing gut bacteria and are positively correlated with disease activity in pediatric IBD patients; ii) D-lactate free multi-strain probiotic supplementations can reduce the abundance of D-lactate producing bacteria and extenuate the disease severity. Overall, this study combines thoroughly multi-omics pipeline with non-invasive D-lactate measurements to understand the possibility of reduction of D-lactate burden in pediatric IBD patients via multi-strain probiotic supplementation.

The characterization of the small bowel microbiota in patients with rectal cancer.

The characterization of the human microbiome and its role in maintaining the physiological homeostasis in our body as well as the role in various diseases has emerged into a highly relevant research field in the past years.  To date, a majority of studies involve the fecal microbiome due to the convenient accessibility. However, much less is known about the small bowel microbiome due to limited accessibility and rapid luminal flow. Physiological function of the small bowel relies critically on the mucosal integrity, which in turn is significantly influenced by gut microbiota. It is well accepted that the small bowel microbiota plays an important role in the nutritional/metabolic status as well as the immune status of the host. Patients with ileostomies represent a perfect source to investigate the dynamic of small bowel microbiota. Moreover, the repetitive sampling of small bowel effluent without adding any distress to the study participants makes more appealing to investigate the compositional changes in the gut over time. We investigate the composition of the small bowel microbiome in patients with ileostomies undergoing surgery for rectal cancer. Robust data of the composition of the small bowel microbiota is scarce. This study adds valuable detail of the composition of the small bowel microbiota, and it is the first attempt to correlate the data to clinical outcome measures. This study aims to provide the background needed for future interventional studies where the small bowel microbiome could be influenced and targeted as for instance by dietary interventions.