Welcome to the IUMS 2022 Interactive Program

Background and Aims

In recent years, the mammalian gut has emerged as a fundamentally important microbial environment. Intriguingly, in special cases, complete obligatory dependence exists between the host and its associated microorganisms, whereby the microbial communities perform fundamental processes, such as digestion of the feed for the host. Among the most representative and ecologically relevant examples are ruminants – foregut fermenters that rely critically on their associated gut microbes to digest their plant feed. Due to this paradigmatic obligatory dependence of the host on its microbiome, such systems serve as excellent models to understand fundamental aspects of the ecological and evolutionary relationships between hosts and their microbes. In my lecture, I will discuss some of our recent findings of the rumen microbiome ecosystem stability, development, and interaction with the host.

Background and Aims

Alterations in the gut microbiota have been associated with Celiac Disease (CeD); however, the contribution of individual microbial species to the overall functional activity of the microbiota (i.e., the gut metabolome) and their role in CeD pathogenesis are largely unknown. This is because existing functional profiling approaches merely enumerate functional pathways encoded by metagenomes but do not provide any information about what microbes carry what pathways or produce what metabolites. To address this gap, we leveraged data from a perspective birth cohort study of infants at high risk of CeD to functionally profile their gut microbiota at species and molecular level resolution.

Methods

We used 167 fecal metagenomes collected longitudinally from ten children who developed CeD and ten controls to construct genome-scale models of metabolism for 359 microbial species in these samples. The models for species present in each sample were then integrated to build sample-specific species-resolved models of the entire gut microbiota metabolism.

Results

By computationally simulating these models, we could track back individual microbial species producing specific secreted metabolites. We identified 18 (out of 2,120) species-metabolite pairs involving nine species and 14 metabolites, that were significantly different between cases and controls (Wilcox, p < 0.05). Some of these metabolites were previously implicated in CeD or inflammation, e.g., L-tryptophan, arabinose, xanthine, and cholic acid that are linked to species of Bacteroides, Bifidobacterium, and Blautia in our models.

Conclusions

Overall, this study provides a roadmap for mechanistically linking microbial and molecular markers of CeD in the gut.

Background and Aims

Development of the gut microbiome occurs in early life. Previous studies provide evidence for an association between gut microbiota modifications and the development of food allergies. Nutritional interventions have been proposed to support food tolerance development by altering the gut microbiome. We aim to gain insight into microbial and functional differences related to outgrowth of cow’s milk allergy (CMA) and nutritional interventions.

Methods

This study included 120 faecal samples of the PRESTO clinical trial (NTR3725), where 40 infants with CMA were monitored after diagnosis, as well as 6 and 12 months after a nutritional intervention with standardized amino acid formula or similar formula with a synbiotic blend (oligosaccharides (oligofructose, inulin) + Bifidobacterium breve). Twenty-four out of forty infants showed outgrowth of CMA after 12 months. We performed 16S rRNA sequencing and metaproteomics analysis of the bacterial gut microbiome.

Results

Outgrowth of CMA was characterized by significantly higher levels of proteins produced by some members of the core gut microbiota. Significantly higher levels of Bifidobacteriaceae and several microbial proteins were observed after treatment with synbiotics. The synbiotic group also had higher levels of several bifidobacterial carbohydrate-active enzymes, known to metabolize oligosaccharides.

Conclusions

Apart from studying the microbiome, metaproteomics also allows to study protein expression. By combining metaproteomics and 16S rRNA sequencing, several microbial and functional differences related to outgrowth of CMA and nutritional interventions could be revealed.

Acknowledgement: Guus Roeselers and Heleen de Weerd (Danone-Nutricia Research) for input in the study design and pre-processing 16S rRNA data respectively.

Background and Aims

Human gut microbial communities are known to vary geographically. It is important to understand the nature of geographical influences in order to get an overall picture of how gut microbial community affects overall health. In this study, we have explored available human gut microbiome sequence datasets of individuals representing different geographical realms to map geographical influences on gut microbial community structure and identified factors that shaped the observed trends.

Methods

Selected datasets representing United States of America (PRJNA471742), Chile (PRJEB16755), South Africa (PRJEB40733), Kuwait (PRJNA554702) and Malaysia (PRJNA631204) were considered based on commonality in sequencing chemistry approach and overlap of the 16S rRNA molecule. As part of this study 13,52,59,399 number of sequences were analysed using computational biology approaches.

Results

It was observed that diet, lifestyle and geographical separation causes significant difference in gut microbial community structure. Firmicutes and Bacteroidetes were the most dominant phyla among all populations but Actinobacteria was exclusively present in high abundance in Malaysian populations (15.99%). Alpha diversity analysis (Shannon indices) showed that Malaysian population had highest diversity. Beta diversity analyses estimated using PCA and PCoA analyses showed that Chilean population formed a distinct cluster among all the studied populations.

Conclusions

The study suggests that not just geographical separation but a combined effect of geographical separation, modern lifestyle, food habits and several linked factors structure gut microbiome their functions and ultimately influence overall health.