On the origins of species: Host-Microbiome-Diet interactions in early life
Division 2: Liver and Digestive Health
Department of Medical Microbiology
Background
Consequently, unraveling the complex host-microbiome-diet interactions during this window-of-opportunity is pivotal to find new leads to prevent the development of non-communicable diseases. Combining epidemiological human birth cohorts, clinical trials, in vitro models and murine in vivo models, we aim to understand the natural process of the maturation of the microbiota and the impact of host, environmental and dietary factors in this process. We have, for example, recently demonstrated the causal impact of bile acids in neonatal microbiota development (van Best et al., Nature Communications 2020). In addition, the impact of human milk oligosaccharides as well as factors of the host’s innate immune system that shape the microbiota composition and thus ensure a beneficial outcome and host-microbial homeostasis after the postnatal period are being investigated. In addition, the role of microbial perturbations in the onset of non-communicable diseases are main topics within our research. This is exemplified a RCT (PROTEA-study) on the prevention of respiratory infections and allergies in premature neonates by administrating bacterial lysates, a study facilitated by a Netherlands Lung Foundation consortium grant that will start shortly.
Major breakthroughs
We have recently for the first time demonstrated how joint modelling (integration of longitudinal microbiome analysis and survival analysis) can be used to unravel microbial perturbations prior to disease onset (Galazzo et al., Gastroenterology 2020).
- Within our PROTEA-study, we expect to reduce respiratory infections and comorbidities after preterm birth and thereby significantly enhance the quality of life in this vulnerable population.
- By focusing on integrative multi-omics and innovative single cell phenotyping approaches, we strive to markedly deepen the knowledge on the functional development of the infant microbiota and its interaction with the host.
Scientific impact/Research quality
Selection of publications
- van Best N, Rolle-Kampczyk U, Schaap FG, Basic M, Olde Damink SWM, Bleich A, Savelkoul PHM, von Bergen M, Penders J, Hornef MW (2020). Bile acids drive the newborn’s gut microbiota maturation. Nature Communications, 11(1), 3692, DOI: 10.1038/s41467-020-17183-8.
- van Best N, Trepels-Kottek S, Savelkoul P, Orlikowsky T, Hornef, MW, Penders, J (2020). Influence of probiotic supplementation on the developing microbiota in human preterm neonates. Gut Microbes, 12(1), 1-16. DOI: 10.1080/19490976.2020.1826747.
- Galazzo G, van Best N, Bervoets L, Dapaah I, Savelkoul PH, Hornef MW, Lau S, Hamelmann E, Penders, J (2020). Gastroenterology, 158(6), 1584-1596, DOI: 10.1053/j. gastro.2020.01.024.
- Fassarella M, Blaak EE, Penders J, Nauta A, Smidt H, Zoetendal EG (2020). Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health. Gut, DOI:10.1136/gutjnl-2020-321747. Epub ahead of print. PMID: 33051190.
- Zhong H, Penders J, Shi Z, Ren H, Cai K, Fang C, Ding Q, Thijs C, Blaak EE, Stehouwer CDA, Xu X, Yang H, Wang J, Wang J, Jonkers DMAE, Masclee AAM, Brix S, Li J, Arts ICW, Kristiansen K (2019). Impact of early events and lifestyle on the gut microbiota and metabolic phenotypes in young school-age children. Microbiome 7(1):2. DOI: 10.1186/s40168-018-0608-z.
Who is involved?
Dr. J. Penders (PI), Dr. Niels van Best (post-doc, joint-PhD UM-RWTH Aachen), Drs. G. Galazzo (PhD-student), Drs. David Barnett (external PhD-student at Maastricht Center for Systems Biology), Drs. Bich Ngoc (external PhD at Oxford University Clinical Research Unit, Hanoi, Vietnam), Dr. Giang Le (bioinformatician) and Christel Driessen and Mayk Lucchesi (supportive staff).
Our team’s research is characterised by a multi-disciplinary approach combining fundamental and applied research to gain insight in early-life microbiome development. Importantly, translation of novel mechanistic insights into diagnostic, prognostic and therapeutic improvement is always pursued. Epidemiological studies (LucKi Birth cohort, KOALA Birth Cohort, Asthma Early Detection study) are conducted in collaboration with clinical (Paediatrics; Obstetrics & Gynaecology) and non-clinical (Epidemiology) departments within our faculty. Moreover, our team is responsible for the microbiome research in birth cohorts and clinical trials conducted at other university medical centres within the Netherlands and abroad (e.g., Erasmus MC, RWTH Uniklinik Aachen and Charité Universitätsmedizin Berlin).
Users and collaborations
Our research on early-life host-microbe-diet interactions is embedded in several ambitious international networks, incl.:
- the Million Microbiomes of Humans Project (J. Penders - member steering committee, https://db.cngb.org/mmhp), which aims to establish a reference catalogue of human microbiomes across age and geography;
- the InViVo Planetary Health Network (J. Penders co-Director, www.invivoplanet.com), which aims to transform personal and planetary health through awareness, attitudes and actions and to have a deeper understanding of how all systems are interconnected and interdependent, and;
- the JPI Knowledge Platform on Food, Diet, Intestinal Microbiomics and Human Health, which aims to standardise, harmonise and share data and knowledge.
We furthermore collaborate with various academic partners (a.o. Uniklinik RWTH Aachen, University of Liège, Wageningen University & Research, McMaster University, Washington University, McMaster University, Charité, DTU Copenhagen, OUCRU Hanoi), as well as industrial partners (a.o. InBiome, Symbiopharm, FrieslandCampina).
Funding
The research is funded by grants from the Joint Programmes Initiative a Healthy Diet for a Healthy Live, a NWO-VIDI grant (to J. Penders), Carbohydrate Competence Center NWO Carbobiotics, a Lung Foundation Consortium Grant, EFSD/Chinese Diabetes Society/Lilly and a Kootstra Talent Fellowship (to N. van Best).
Figure 1
Societal impact
Our research is focused on healthy microbiome development in early-life for a healthy life and explicitly multiple stakeholders. The Lucki Gut Birth Cohort (www.luckigut.nl) is, for example, embedded within the Youth Health Care (JGZ) and as such close interactions with stakeholders including paediatricians and nurses of child health clinics, but also midwives, maternity care and lactation specialists is warranted. Research tools (R packages and codes, e.g., MicroViZ) developed within our team are shared with the scientific community via our lab’s GitHub. Our team is often invited to present results on the early life microbiome and its role in non-communicable diseases at various (inter)national congresses (e.g., EAACI, ESPEN, International Human Microbiome Congress, German Allergy Congress, Nordic Allergy Symposium, Beneficial Microbes Conference).
Media exposure
| Source | Title |
| Algemeen Dagblad, 20 November 2020 | Onderzoek naar voorkomen longontsteking bij te vroeg geboren baby’tjes |
| www.gutmicrobiotaforhealth.com, January 2019 |
Gut microbiome development continues between 6 and 9 years of age, with pre-school diet and breastfeeding acting as major driving forces |
| www.limburger.nl, 23rd January 2020 |
Minder allergieën bij jonge kinderen met goede darmflora |
| Nederlands Dagblad, 21 January 2020 | Darmflora van baby’s bepalend voor allergieën |
| Gezond idee, June 2017 | Hoe houd je je darmflora gezond? |
| Gezond idee, October 2016 | Bacteriën als slankmakers |
Future perspectives
Our research in the next five years will focus on generating a deeper functional understanding of the developing infant microbiota and its interaction with the host by integrative multi-omics (metabolomics, metagenomics, meta-transcriptomics) as well as single-cell phenotyping approaches. Together this should further unravel the ecological processes of microbiota maturation as well as identify (non)responders to microbiota-targeted interventions. In order to achieve this and maintain a strong international position, we have recently joined forces with partners at Uniklinik RWTH Aachen, the Centre for Healthy Eating & Food Innovation (HEFI) at Campus Venlo and University of Liège to launch the Euregional Microbiome Center (EMC).
By establishing a prestigious training and research climate, initiating joint-PhD projects and exchanging students between EMC partner institutes, we strive to be a breeding ground for the next-generation of leading scientists.