Role of the microbiome in human development

Domínguez-Bello, María Gloria; Godoy-Vitorino, Filipa; Knight, Rob; Blaser, Martin J.

doi:10.1136/gutjnl-2018-317503

Cited by 617 publications

(457 citation statements)

References 111 publications

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“…The importance of intestinal commensal bacteria in regulation of the intestinal barrier function and immune development during infancy is well established 36, 37 . Yet, specifically the symbiotic role of the breastmilk-promoted Bifidobacterium species, which are highly abundant in breastfed infants, remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Breastmilk-promoted bifidobacteria produce aromatic amino acids in the infant gut

Laursen

Sakanaka

Burg

et al. 2020

Preprint

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26Breastfeeding profoundly shapes the infant gut microbiota, which is critical for early life immune 27 development. However, few breastmilk-dependent microbial metabolites mediating host-microbiota 28 interactions are currently known. We here demonstrate that breastmilk-promoted Bifidobacterium 29 species convert aromatic amino acids (tryptophan, phenylalanine and tyrosine) into their respective 30 aromatic lactic acids (indolelactate, phenyllactate and 4-hydroxyphenyllactate) via a previously 31 unrecognised aromatic lactate dehydrogenase. By longitudinal profiling of the gut microbiota 32 composition and metabolome of stool samples of infants obtained from birth until 6 months of age, 33 we show that stool concentrations of aromatic lactic acids is determined by the abundance of human 34 milk oligosaccharide degrading Bifidobacterium species containing the aromatic lactate 35 dehydrogenase. Finally, we demonstrate that stool concentrations of Bifidobacterium-derived 36 indolelactate are associated with the capacity of infant stool samples to activate the aryl 37 hydrocarbon receptor, a receptor important for maintenance of intestinal homeostasis and immune 38 system development. These findings open up new directions towards understanding the role of 39 breastmilk-promoted Bifidobacterium in mediating host-microbiota interactions in early life. 40 INTRODUCTION 41Human breastmilk is a perfectly adapted nutritional supply for the infant 1 . Breastfeeding provides 42 children with important short-term protection against infections, and may also provide long-term 43 metabolic benefits 1,2 . These benefits may partly be mediated through the gut microbiota, since 44 breastfeeding is the strongest determinant of gut microbiota composition and function during 45 infancy 3-5 . Human breastmilk contains human milk oligosaccharides (HMOs), which are complex, 46 highly abundant sugars serving as substrates for specific microbes including certain species of 47 Bifidobacterium 6 . This co-evolution between bifidobacteria and the host, mediated by HMOs, to a 48 large extent directs the colonization of the gut in early life, which has critical impact on the immune 49 system 7 . Depletion of specific microbes, including Bifidobacterium, in early life has been associated 50 with increased risk of allergy and asthma development in childhood 8,9 , and is suggested to 51 compromise immune function and lead to increased susceptibility to infectious disease 10,11 . Despite 52 Bifidobacterium dominating the gut of breastfed infants and being widely acknowledged as 53 beneficial, mechanistic insights on the contribution of these bacteria and their metabolites to 54 immune development during infancy remain limited. Recent studies show that microbial aromatic 55 amino acid metabolites including tryptophan-derived indoles 12 , via activation of the aryl 56 hydrocarbon receptor (AhR), can fortify the intestinal barrier 13,14 , protect against pathogenic 57 infections 15,16 and influence host metabolism 13,17,18 , which makes this...

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Section: Discussionmentioning

confidence: 99%

Breastmilk-promoted bifidobacteria produce aromatic amino acids in the infant gut

Laursen

Sakanaka

Burg

et al. 2020

Preprint

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“…Cross denotes mean. and saliva microbiome seems to be related to health in opposing ways 11,38 . Still, this positive correlation could be related to the degree to which individuals are exposed to environmental bacteria.…”

Section: Discussionmentioning

confidence: 99%

Response of the human gut and saliva microbiome to urbanization in Cameroon

Lokmer

Aflalo

Amougou

et al. 2020

Sci Rep

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Urban populations from highly industrialized countries are characterized by a lower gut bacterial diversity as well as by changes in composition compared to rural populations from less industrialized countries. to unveil the mechanisms and factors leading to this diversity loss, it is necessary to identify the factors associated with urbanization-induced shifts at a smaller geographical scale, especially in less industrialized countries. to do so, we investigated potential associations between a variety of dietary, medical, parasitological and socio-cultural factors and the gut and saliva microbiomes of 147 individuals from three populations along an urbanization gradient in cameroon. We found that the presence of Entamoeba sp., a commensal gut protozoan, followed by stool consistency, were major determinants of the gut microbiome diversity and composition. interestingly, urban individuals have retained most of their gut eukaryotic and bacterial diversity despite significant changes in diet compared to the rural areas, suggesting that the loss of bacterial microbiome diversity observed in industrialized areas is likely associated with medication. finally, we observed a weak positive correlation between the gut and the saliva microbiome diversity and composition, even though the saliva microbiome is mainly shaped by habitat-related factors.Humans living in urban areas from highly industrialized countries host less diverse gut microbiomes than those in rural areas from the less industrialized ones. This effect of industrialization (as we refer to it hereafter) has been reported by numerous studies comparing urban areas in Europe or North America with rural ones in Africa, Asia or South America 1-8 . Loss in alpha diversity is further accompanied by systematic shifts in bacterial composition (see e.g. 9,10 ). Despite crucial implications for human health 11,12 , the factors responsible for these ecological changes are still unclear. Two main (non-exclusive) hypotheses have been proposed: (i) decreased consumption of dietary fibers 13,14 and (ii) improved sanitation and access to medical care (including antibiotics 15 ). In addition, geographical latitude could be a confounding factor, given that it is a proxy for the diversity of environmental bacteria 16 . Indeed, the only two studies that did not find a loss of diversity with industrialization were studies considering rural populations not living in a warm tropical environment 17,18 .To disentangle various factors potentially leading to this observed diversity loss, some authors focused on smaller geographical scales, contrasting urban and rural individuals from the same countries (referred to hereafter as the effect of urbanization). Such studies reported inconsistent results: no significant differences in Russia 19 and Nigeria 20 , some differences in China 21 , and season and altitude dependent shifts in Mongolia 22 and India 23 , respectively. These discrepancies can be partially explained by different definitions of rural areas used in these studies (from iso...

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“…During early life the gut microbiota plays a key role in development and maturation of numerous host responses [5]. A central interface mediating these interactions is the intestinal lumen, which represents a unique ecological environment that is the major site for microbialhost crosstalk.…”

Section: Introductionmentioning

confidence: 99%

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

Hughes

Schofield

Dalby

et al. 2019

Preprint

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AbstractThe gut microbiota plays a crucial role in regulating and maintaining the epithelial barrier, particularly during early life. Notably, patients with chronic intestinal inflammation have a dysregulated process of renewal and replenishment of the intestinal epithelial cell (IEC) barrier, which is linked to disturbances in the gut microbiota. To date, there are no studies focussed on understanding the impact of inflammatory cell shedding events during the early life developmental window, and which host and microbial factors mediate these responses. Here we sought to determine pathological cell shedding outcomes throughout the postnatal developmental period (day 14, 21, 29 and week 8). Surprisingly neonatal mice (day 14 and 21) were highly refractory to induction of cell shedding after intraperitoneal administration of LPS, with day 29 mice showing strong pathological responses, more similar to those observed in adult mice. These differential responses were not linked to defects in the cellular mechanisms and pathways known to regulate cell shedding responses, although we did observe that neonatal mice had elevated anti-inflammatory (IL-10) responses. Notably, when we profiled microbiota and metabolites from these mice, we observed significant alterations. Neonatal mice had high relative abundances of Streptococcus, Escherichia and Enterococcus and increased primary bile acids. In contrast, older mice were dominated by Candidatus Arthromitus, Alistipes and Lachnoclostridium, and had increased concentrations of SCFAs and methyamines. Faecal microbiota transplant (FMT) and antibiotic studies confirmed the importance of early life gut microbiota in cell shedding responses. In these studies, neonates treated with antibiotics restored LPS-induced small intestinal cell shedding, whereas adult FMT alone had no effect. Our findings further support the importance of the early life window for microbiota-epithelial interactions in the presence of inflammatory stimuli and highlight areas for further investigation to probe underlying mechanisms to drive therapeutic development within the context of chronic inflammatory intestinal diseases.

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Role of the microbiome in human development

Cited by 617 publications

References 111 publications

Breastmilk-promoted bifidobacteria produce aromatic amino acids in the infant gut

Breastmilk-promoted bifidobacteria produce aromatic amino acids in the infant gut

Response of the human gut and saliva microbiome to urbanization in Cameroon

The early life microbiota protects neonatal mice from pathological small intestinal epithelial cell shedding

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