Elevated Fecal pH Indicates a Profound Change in the Breastfed Infant Gut Microbiome Due to Reduction of
            <i>Bifidobacterium</i>
            over the Past Century

Henrick, Bethany M.; Hutton, Andra; Palumbo, Michelle; Casaburi, Giorgio; Mitchell, Ryan D.; Underwood, Mark A.; Smilowitz, Jennifer T.; Frese, Steven A.

doi:10.1128/msphere.00041-18

Cited by 137 publications

(148 citation statements)

References 31 publications

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“…Safe and cost‐effective approaches for the prevention of childhood‐onset type 1 diabetes that could ultimately be administered to all infants in a public health manner are required. The keystone commensal microbe B. infantis has disappeared as the predominant microbe in the infant microbiota in the developed world, and we hypothesize that restoring B. infantis colonization early in infancy will prevent childhood‐onset type 1 diabetes through effects on immune training, prevention of dysbiosis and altered intestinal permeability, and enhanced β‐cell function and survival. In contrast to most probiotics, B. infantis stably and safely colonizes the intestine at high abundance in breastfed infants delivered either vaginally or by Cesarean section .…”

Section: Resultsmentioning

confidence: 99%

“…The rarity (<5% prevalence) of B. infantis colonization of Japanese women late in pregnancy ( n = 100) of whom 100% were colonized with Bifidobacterium contrasts markedly with the frequency of detection of other species of Bifidobacterium . Concomitant with disappearance of intestinal colonization with Bifidobacterium and B. infantis in infancy in the developed world, is an increase in infant fecal pH by as much as 1.5 pH units in breastfed infants over the last century, which likely reflects the decreased production of SCFA and lactate arising from the reduction in Bifidobacterium colonization and absence of B. infantis, which was historically their major source in stools of breastfed infants …”

Section: Disappearing Microbes Are No Longer Colonizing the Intestinamentioning

confidence: 99%

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Prospects for primary prevention of type 1 diabetes by restoring a disappearing microbe

Insel¹,

Knip

2018

Pediatr Diabetes

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Prevention of childhood-onset type 1 diabetes has become more urgent with its marked increased incidence in recent decades in the modern world. Temporally associated with the rising incidence of type 1 diabetes, as well as other autoimmune and allergic diseases in childhood in modern times, is the disappearance of Bifidobacterium and specifically Bifidobacterium longum subsp. infantis (B. infantis) predominance in the intestinal microbiota of breastfed, vaginally-delivered infants. B. infantis efficiently metabolizes human milk oligosaccharides (HMOs) without cross-feeding free sugar monomers to other commensals or pathogens and thereby dominates the intestinal microbiota of breastfed infants. Increased levels of short-chain fatty acids (SCFA), which stimulate both immunoregulation and healthy intestinal and pancreatic β-cell function, are generated by B. infantis. Based on recent observations of the intestinal microbiota in early life in young children who develop type 1 diabetes and demonstration of the robust preventive effects of SCFA in animal models of autoimmune diabetes, we hypothesize that restoring a B. infantis-dominant microbiota early in infancy will prevent islet autoimmunity and childhood-onset type 1 diabetes.

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Section: Resultsmentioning

confidence: 99%

Section: Disappearing Microbes Are No Longer Colonizing the Intestinamentioning

confidence: 99%

Prospects for primary prevention of type 1 diabetes by restoring a disappearing microbe

Insel¹,

Knip

2018

Pediatr Diabetes

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“…Furthermore, with the spread of technology and increasingly rapid turn‐around times, the cost of microbial testing is expected to reduce further over time. These are already used for Clostridium difficile detection and Bifidobacterium level analyses and in a prior study stool and salivary analyses could be used to detect HE in patients with cirrhosis …”

Section: Discussionmentioning

confidence: 99%

“…These are already used for Clostridium difficile detection and Bifidobacterium level analyses and in a prior study stool and salivary analyses could be used to detect HE in patients with cirrhosis. 17,30,31 Cost-effectiveness is one of the major steps towards demonstrating the value of strategies that are perceived to be expensive or difficult to arrange. This has recently been shown for perceived expensive therapeutic options such as directly acting anti-virals and with strategies for screening for hepato-cellular cancer, among others.…”

Section: Discussionmentioning

confidence: 99%

Cost‐effectiveness of integrating gut microbiota analysis into hospitalisation prediction in cirrhosis

et al. 2020

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Summary Background Admissions in cirrhosis are expensive and often unpredictable based on purely clinical variables. Admissions could be related to complications associated with gut microbial changes, which can improve prognostication. However, the cost‐effectiveness remains unclear. Aims Determine cost‐effectiveness of adding gut microbiota analysis to clinical parameters in prediction and subsequent reduction of admissions in cirrhosis. Methods Using a Markov model of 1000 cirrhosis patients over 90 days, we modelled microbiota testing using 16srRNA ($250/sample), low‐depth ($350/sample) and high‐depth ($650/sample) metagenomics added to standard‐of‐care (SOC) for prevention of admissions using standard outcome costs and rates of development. We generated quality of life years (QALY) and Incremental cost‐effectiveness ratios (ICER) for the base scenarios and performed sensitivity analyses by varying costs for outcomes (transplant, death, admission) and admission rates (40%, range 25%‐60%). Results Using fixed costs of outcomes and outcome rates, microbiota analysis was cost‐saving ($47K‐$97K) at $250 and $350/sample if admissions were reduced by 5% over SOC and >10% with $650/sample. When costs of liver transplant, death and admissions were varied, these cost‐savings remained robust provided there was >2.1% reduction (range 1.3%‐3.2%) for $250/sample, >2.9% (range 1.8%‐4.4%) for $350/sample and >5.4% (range 3.3%‐8.2%) for $650/sample. These cost‐savings remained robust even when the assumed admission rate was varied for all sample cost values. Conclusions Gut microbiota analysis is cost‐effective for predicting and potentially preventing 90‐day admissions in cirrhosis over current SOC. This cost‐saving remained robust even after sensitivity analyses that varied the background admission rates.

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“…Microbial fermentation of nondigestible carbohydrates in the gut of exclusively breast-fed infants leads to a relatively high concentration of acetate and lactate (a relative strong acid with pKa= 3.86) (Pham et al 2016, Wopereis et al 2017. Hence, infants have a lower faecal pH than that of adults (Henrick et al 2018, Oozeer et al 2013. The pH of the gut lumen has a significant impact on the microbiota composition , Walker et al 2005.…”

Section: Host-secreted Glycans Support Butyrogenesis In the Gut Micromentioning

confidence: 99%

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

Chia¹

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Chapter 4Microbial metabolic networks at the mucus layer lead to dietindependent butyrate and vitamin B12 production by intestinal symbionts 71 Chapter 5Deciphering trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach 97 Chapter 6General discussion 123 Chapter 7 Thesis summary & Nederlandse samenvatting 143 Appendices References 153Co-author affiliations 179Acknowledgements 183About the author 184List of publications 185 VLAG training activities 186Chapter 1 General introduction and thesis outlineChapter 1 2 General introductionHumans can be considered holobionts, consisting of cells from the host and an even larger number of microorganisms (Postler and Ghosh 2017). The majority of microbes are residing in the gut (Sender et al 2016). The human gut microbiota is a complex ecosystem consisting of bacteria, archaea, microeukaryotes and viruses (Clemente et al 2012). Over 2000 species-level phylotypes (prokaryotes including bacteria and archaea) have been detected for the gut microbiota, with each individual estimated to host at least 160 species (Qin et al 2010, Zoetendal et al 2008. The gut microbiota may impact the well-being of human and susceptibility for diseases by interacting with our metabolic, immune and neurological system (Honda and Littman 2016, Koh et al 2016, Rogers et al 2016. Furthermore, the gut microbiota contributes to a variety of metabolic functions and can be seen as an essential part of our digestive system (El Kaoutari et al 2013). Bacterial symbionts allow the human hosts to utilise inaccessible nutrients by converting complex substrates to short chain fatty acid (SCFA) and vitamins (Fisher et al 2017). Bacterial-derived SCFAs are estimated to contribute about 10% of our daily caloric requirement (Bergman 1990). While all SCFAs are vital for maintaining gut homeostasis, butyrate is of particular interest because it has been attributed to a range of health-promoting functions. Butyrate is the primary energy source for colonic epithelial cells and is associated with the enhancement of colonic barrier function, increase of satiety, pain relief, anti-inflammatory responses, and protection against colorectal cancer (Banasiewicz et al 2013, Bolognini et al 2016, Donohoe et al 2011, Furusawa et al 2013, Goncalves and Martel 2013.Considering the physiological benefits of butyrate to human health, this thesis investigates the microbial interaction of gut symbionts that support butyrate production driven primarily by the host produced glycans in human milk and mucus. Glycans are compounds consisting of an array of glycosidically linked monosaccharides (monosaccharides and disaccharides are collectively termed sugars) such as human milk oligosaccharides (HMOS) and mucins (Varki and Kornfeld 2017). HMOS present in mother milk are the major compositional and functional driver of the infant gut microbiota (Backhed et al 2015). Mucin glycans covering the intestinal lining create a stable niche for bacterial coloni...

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Elevated Fecal pH Indicates a Profound Change in the Breastfed Infant Gut Microbiome Due to Reduction of Bifidobacterium over the Past Century

Abstract: Historically, Bifidobacterium species were reported as abundant in the breastfed infant gut. However, recent studies in resource-rich countries show an increased abundance of taxa regarded as signatures of dysbiosis.

Cited by 137 publications

References 31 publications

Prospects for primary prevention of type 1 diabetes by restoring a disappearing microbe

Prospects for primary prevention of type 1 diabetes by restoring a disappearing microbe

Cost‐effectiveness of integrating gut microbiota analysis into hospitalisation prediction in cirrhosis

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

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