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

mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Bethany M. Henrick ◽  
Andra A. Hutton ◽  
Michelle C. Palumbo ◽  
Giorgio Casaburi ◽  
Ryan D. Mitchell ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Species Abundance ◽  
Breastfed Infant ◽  
Past Century ◽  
Breastfed Infants ◽  
The Past ◽  
Gut Function ◽  
Infant Gut Microbiome ◽  
Fecal Ph ◽  
Rich Countries

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. It is unclear whether these differences are the product of genetics, geographic factors, or interventions such as formula feeding, antibiotics, and caesarean section. Fecal pH is strongly associated with Bifidobacterium abundance; thus, pH could be an indicator of its historical abundance. A review of 14 clinical studies published between 1926 and 2017, representing more than 312 healthy breastfed infants, demonstrated a change in fecal pH from 5.0 to 6.5 (adjusted r 2 = 0.61). This trend of increasing infant fecal pH over the past century is consistent with current reported discrepancies in Bifidobacterium species abundance in the gut microbiome in resource-rich countries compared to that in historical reports. Our analysis showed that increased fecal pH and abundance of members of the families Enterobacteriaceae , Clostridiaceae , Peptostreptococcaceae , and Veillonellaceae are associated, indicating that loss of highly specialized Bifidobacterium species may result in dysbiosis, the implications of which are not yet fully elucidated. Critical assessment of interventions that restore this ecosystem, measured by key parameters such as ecosystem productivity, gut function, and long-term health, are necessary to understand the magnitude of this change in human biology over the past century.

scholarly journals Dynamic Associations of Milk Components With the Infant Gut Microbiome and Fecal Metabolites in a Mother–Infant Model by Microbiome, NMR Metabolomic, and Time-Series Clustering Analyses

2022 ◽  
Vol 8 ◽  
Author(s):  
Yosuke Komatsu ◽  
Daiki Kumakura ◽  
Namiko Seto ◽  
Hirohisa Izumi ◽  
Yasuhiro Takeda ◽  
...  
Keyword(s):  
Breast Milk ◽  
Gut Microbiome ◽  
Lactation Period ◽  
Bioactive Components ◽  
Fecal Microbiome ◽  
Breastfed Infants ◽  
H Nmr ◽  
Milk Components ◽  
Infant Gut Microbiome ◽  
Infant Feces

Background: The gut microbiome and fecal metabolites of breastfed infants changes during lactation, and are influenced by breast milk components. This study aimed to investigate dynamic associations of milk components with the infant gut microbiome and fecal metabolites throughout the lactation period in a mother–infant model.Methods: One month after delivery, breast milk and subsequent infant feces were collected in a pair for 5 months from a mother and an exclusively breastfed infant. Composition of the fecal microbiome was determined with 16S rRNA sequencing. Low-molecular-weight metabolites, including human milk oligosaccharides (HMOs), and antibacterial proteins were measured in feces and milk using 1H NMR metabolomics and enzyme-linked immunosorbent assays. The association of milk bioactive components with the infant gut microbiome and fecal metabolites was determined with Python clustering and correlation analyses.Results: The HMOs in milk did not fluctuate throughout the lactation period. However, they began to disappear in infant feces at the beginning of month 4. Notably, at this time-point, a bifidobacterium species switching (from B. breve to B. longum subsp. infantis) occurred, accompanied by fluctuations in several metabolites including acetate and butyrate in infant feces.Conclusions: Milk bioactive components, such as HMOs, might play different roles in the exclusively breastfed infants depending on the lactation period.

scholarly journals Maximizing Nutrient Availability for the Breastfed Infant Through Colonization with B. Infantis EVC001 (FS04-04-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Tracy Shafizadeh ◽  
Steve Frese ◽  
Giorgio Casaburi
Keyword(s):  
Human Milk ◽  
Nutrient Availability ◽  
Gut Microbiome ◽  
Bifidobacterium Longum ◽  
Developed Countries ◽  
Breastfed Infant ◽  
Control Group ◽  
Term Infants ◽  
Fecal Samples ◽  
Infant Gut Microbiome

Abstract Objectives Human breastmilk contains complete nutrient composition required for the developing infant, including human milk oligosaccharides (HMO). These complex carbohydrates are indigestible by the infant alone, and require digestion by gut microbes, namely Bifidobacterium longum subsp. infantis (B. infantis). However, decades of C-section delivery, formula feeding and increasing exposure to antibiotics have contributed the loss of this critical infant-associated gut bacterium in developed countries. Therefore, restoring B. infantis to the infant gut was hypothesized to improve the nutritional utilization of human breastmilk in healthy term infants. Methods In an open trial, healthy, exclusively breastfed term infants were fed 1.8 × 1010 CFU B. infantis EVC001 daily from day 7–27 postnatal (n = 34; EVC001-fed), or breastmilk alone (n = 32; control group). Fecal samples, milk samples, and weekly self-reported data were collected and analyzed for infant gut microbiome composition and function, human milk oligosaccharide composition, and fecal metabolites. 16S rRNA sequencing and shotgun metagenome sequencing provided characterization of microbial communities from birth through 60 days postnatal. Results Infants fed B. infantis EVC001 were uniformly colonized with this organism at 1011 CFU/g feces, while infants in the control group had a median total Bifidobacterium level below 10^5 CFU/g feces, despite exclusive breastfeeding. Mass spectrometry of fecal samples from B. infantis EVC001-fed infants showed that the resulting microbial community produced higher concentrations of lactate and acetate and lower excretion of HMO, while control infants showed significantly lower ability to capture and utilize these carbohydrates from human milk. Importantly, HMO content of breastmilk was not significantly different between groups and no difference was found in the gut microbiome of infants based on secretor status of mothers (presence or absence of 2’FL in breastmilk). Further, these changes were associated with reductions in taxa that have been associated with negative health outcomes including colic, asthma, eczema and allergy. Conclusions Overall, colonization with B. infantis is observed to be an effective way to restore maximal function of the infant gut microbiome to improve nutrient availability in the breastfed infant. Funding Sources This study was funded by Evolve BioSystems, Inc.

scholarly journals Persistence of Supplemented Bifidobacterium longum subsp. infantis EVC001 in Breastfed Infants

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Steven A. Frese ◽  
Andra A. Hutton ◽  
Lindsey N. Contreras ◽  
Claire A. Shaw ◽  
Michelle C. Palumbo ◽  
...  
Keyword(s):  
Human Milk ◽  
Gut Microbiome ◽  
Bifidobacterium Longum ◽  
Specific Substrate ◽  
Fecal Microbiome ◽  
Microbiome Composition ◽  
Breastfed Infants ◽  
Gut Function ◽  
First Time

ABSTRACT The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function. Attempts to alter intestinal dysbiosis via administration of probiotics have consistently shown that colonization with the administered microbes is transient. This study sought to determine whether provision of an initial course of Bifidobacterium longum subsp. infantis (B. infantis) would lead to persistent colonization of the probiotic organism in breastfed infants. Mothers intending to breastfeed were recruited and provided with lactation support. One group of mothers fed B. infantis EVC001 to their infants from day 7 to day 28 of life (n = 34), and the second group did not administer any probiotic (n = 32). Fecal samples were collected during the first 60 postnatal days in both groups. Fecal samples were assessed by 16S rRNA gene sequencing, quantitative PCR, mass spectrometry, and endotoxin measurement. B. infantis-fed infants had significantly higher populations of fecal Bifidobacteriaceae, in particular B. infantis, while EVC001 was fed, and this difference persisted more than 30 days after EVC001 supplementation ceased. Fecal milk oligosaccharides were significantly lower in B. infantis EVC001-fed infants, demonstrating higher consumption of human milk oligosaccharides by B. infantis EVC001. Concentrations of acetate and lactate were significantly higher and fecal pH was significantly lower in infants fed EVC001, demonstrating alterations in intestinal fermentation. Infants colonized by Bifidobacteriaceae at high levels had 4-fold-lower fecal endotoxin levels, consistent with observed lower levels of Gram-negative Proteobacteria and Bacteroidetes. IMPORTANCE The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function.

scholarly journals Colonization Resistance in the Infant Gut: The Role of B. infantis in Reducing pH and Preventing Pathogen Growth

2020 ◽  
Vol 9 (2) ◽  
pp. 7 ◽  
Author(s):  
Rebbeca M. Duar ◽  
David Kyle ◽  
Giorgio Casaburi
Keyword(s):  
Bifidobacterium Longum ◽  
Strong Association ◽  
Critical Factor ◽  
Steady Increase ◽  
Past Century ◽  
Industrialized Countries ◽  
Colonization Resistance ◽  
Breastfed Infants ◽  
Fecal Ph ◽  
Acidic Compounds

Over the past century, there has been a steady increase in the stool pH of infants from industrialized countries. Analysis of historical data revealed a strong association between abundance of Bifidobacterium in the gut microbiome of breasted infants and stool pH, suggesting that this taxon plays a key role in determining the pH in the gut. Bifidobacterium longum subsp. infantis is uniquely equipped to metabolize human milk oligosaccharides (HMO) from breastmilk into acidic end products, mainly lactate and acetate. The presence of these acidic compounds in the infant gut is linked to a lower stool pH. Conversely, infants lacking B. infantis have a significantly higher stool pH, carry a higher abundance of potential pathogens and mucus-eroding bacteria in their gut microbiomes, and have signs of chronic enteric inflammation. This suggests the presence of B. infantis and low intestinal pH may be critical to maintaining a protective environment in the infant gut. Here, we summarize recent studies demonstrating that feeding B. infantis EVC001 to breastfed infants results in significantly lower fecal pH compared to controls and propose that low pH is one critical factor in preventing the invasion and overgrowth of harmful bacteria in the infant gut, a process known as colonization resistance.

Can we modulate the breastfed infant gut microbiota through maternal diet?

2021 ◽  
Author(s):  
Azhar S Sindi ◽  
Donna T Geddes ◽  
Mary E Wlodek ◽  
Beverly S Muhlhausler ◽  
Matthew S Payne ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Human Milk ◽  
Gut Microbiome ◽  
Animal Studies ◽  
Maternal Diet ◽  
Breastfed Infant ◽  
Microbial Composition ◽  
Infant Gut Microbiome ◽  
And Function ◽  
Microbiome Data

Abstract Initial colonisation of the infant gut is robustly influenced by regular ingestion of human milk, a substance that contains microbes, microbial metabolites, immune proteins, and oligosaccharides. Numerous factors have been identified as potential determinants of the human milk and infant gut microbiota, including maternal diet; however, there is limited data on the influence of maternal diet during lactation on either of these. Here, we review the processes thought to contribute to human milk and infant gut bacterial colonisation and provide a basis for considering the role of maternal dietary patterns during lactation in shaping infant gut microbial composition and function. Although only one observational study has directly investigated the influence of maternal diet during lactation on the infant gut microbiome, data from animal studies suggests that modulation of the maternal gut microbiota, via diet or probiotics, may influence the mammary or milk microbiota. Additionally, evidence from human studies suggests that the maternal diet during pregnancy may affect the gut microbiota of the breastfed infant. Together, there is a plausible hypothesis that maternal diet during lactation may influence the infant gut microbiota. If substantiated in further studies, this may present a potential window of opportunity for modulating the infant gut microbiome in early life.

scholarly journals Young at Gut—Turning Back the Clock with the Gut Microbiome

2021 ◽  
Vol 9 (3) ◽  
pp. 555
Author(s):  
Harish Narasimhan ◽  
Clarissa C. Ren ◽  
Sharvari Deshpande ◽  
Kristyn E. Sylvia
Keyword(s):  
Gut Microbiome ◽  
Past Century ◽  
Low Grade ◽  
Gut Dysbiosis ◽  
The Past ◽  
Health Measures ◽  
Aging Populations ◽  
Secretory Phenotype ◽  
The Brain

Over the past century, we have witnessed an increase in life-expectancy due to public health measures; however, we have also seen an increase in susceptibility to chronic disease and frailty. Microbiome dysfunction may be linked to many of the conditions that increase in prevalence with age, including type 2 diabetes, cardiovascular disease, Alzheimer’s disease, and cancer, suggesting the need for further research on these connections. Moreover, because both non-modifiable (e.g., age, sex, genetics) and environmental (e.g., diet, infection) factors can influence the microbiome, there are vast opportunities for the use of interventions related to the microbiome to promote lifespan and healthspan in aging populations. To understand the mechanisms mediating many of the interventions discussed in this review, we also provide an overview of the gut microbiome’s relationships with the immune system, aging, and the brain. Importantly, we explore how inflammageing (low-grade chronic inflammation that often develops with age), systemic inflammation, and senescent cells may arise from and relate to the gut microbiome. Furthermore, we explore in detail the complex gut–brain axis and the evidence surrounding how gut dysbiosis may be implicated in several age-associated neurodegenerative diseases. We also examine current research on potential interventions for healthspan and lifespan as they relate to the changes taking place in the microbiome during aging; and we begin to explore how the reduction in senescent cells and senescence-associated secretory phenotype (SASP) interplay with the microbiome during the aging process and highlight avenues for further research in this area.

scholarly journals Restoring Bifidobacterium Infantis EVC001 to the Infant Gut Microbiome Significantly Reduces Intestinal Inflammation (OR12-01-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Bethany Henrick ◽  
Stephanie Chew ◽  
Ryan Mitchell ◽  
Lindsey Contreras ◽  
Giorgio Casaburi ◽  
...  
Keyword(s):  
Immune System ◽  
Gut Microbiome ◽  
Intestinal Inflammation ◽  
System Development ◽  
Fecal Calprotectin ◽  
Breastfed Infants ◽  
Gut Dysbiosis ◽  
Immune System Development ◽  
Infant Gut Microbiome ◽  
Chronic Intestinal Inflammation

Abstract Objectives Several seminal publications identify that Bifidobacterium longum subsp. infantis (B. infantis) has uniquely evolved to be the predominant strain in the breastfed infant gut; however, recent cohort studies indicate it is now far less abundant in infants born in industrialized nations, along with increased abundance of potentially pathogenic bacteria and gut dysbiosis. Importantly, recent clinical studies show enteric dysbiosis during the first 100 days of life can lead to higher risk of allergic and autoimmune-mediated disorders later in life. Given the importance of the microbiome for immune system development, we investigated the effect of B. infantis EVC001 consumption on intestinal inflammation in a cohort of healthy, term infants. Methods Forty (n = 40) infants were randomly selected from the previously conducted clinical study in which healthy, exclusively breastfed infants were either fed B. infantis EVC001 daily for 21 days, starting at day 7 postpartum, or received breastmilk alone. Stool samples were collected at multiple times postnatally and analyzed for cytokine production using a multiplex system and calprotectin ELISA. Results Baseline analysis indicated infants randomized to the EVC001 group produced naturally higher levels of IL2, IL5, IL6, IL10, TNFa and IFNg and lower levels of IL1b (all P < 0.01); however, by day 40, infants fed EVC001 produced significantly decreased cytokines, IL1b, IL6, IL8, IL22, TNFa and IFNg (all P < 0.0001) and IL-5 (P = 0.024), and at day 60 postpartum (all P < 0.001) and IL5 (P = 0.013). Fecal calprotectin concentration was significantly decreased in infants whose gut microbiome contained Bifidobacterium (P = 9.61e-05). Conclusions This study is the first to demonstrate a significant impact of B. infantis EVC001 on immune homeostasis in breastfed infants during a critical window of immune system development. Infants fed EVC001 produced significantly less proinflammatory cytokines and fecal calprotectin compared to control infants. Notably, TNFa, IL1b, and IFNg, which increase intestinal permeability, were significantly elevated in control infants. This may play an important mechanistic role in explaining the chronic intestinal inflammation observed in infants not colonized with B. infantis. These critical data provide a new understanding of the role of the infant gut microbiome in immune system development and provide novel applications to address chronic inflammation through modulation of gut dysbiosis. Funding Sources Industry funded.

The zoonotic potential of bat-borne coronaviruses

2020 ◽  
Vol 4 (4) ◽  
pp. 365-381
Author(s):  
Ny Anjara Fifi Ravelomanantsoa ◽  
Sarah Guth ◽  
Angelo Andrianiaina ◽  
Santino Andry ◽  
Anecia Gentles ◽  
...  
Keyword(s):  
Genetic Material ◽  
Field Research ◽  
Sympatric Species ◽  
Animal Origin ◽  
Mammalian Host ◽  
Past Century ◽  
The Past ◽  
Novel Host ◽  
Horseshoe Bat ◽  
Human Infections

Seven zoonoses — human infections of animal origin — have emerged from the Coronaviridae family in the past century, including three viruses responsible for significant human mortality (SARS-CoV, MERS-CoV, and SARS-CoV-2) in the past twenty years alone. These three viruses, in addition to two older CoV zoonoses (HCoV-229E and HCoV-NL63) are believed to be originally derived from wild bat reservoir species. We review the molecular biology of the bat-derived Alpha- and Betacoronavirus genera, highlighting features that contribute to their potential for cross-species emergence, including the use of well-conserved mammalian host cell machinery for cell entry and a unique capacity for adaptation to novel host environments after host switching. The adaptive capacity of coronaviruses largely results from their large genomes, which reduce the risk of deleterious mutational errors and facilitate range-expanding recombination events by offering heightened redundancy in essential genetic material. Large CoV genomes are made possible by the unique proofreading capacity encoded for their RNA-dependent polymerase. We find that bat-borne SARS-related coronaviruses in the subgenus Sarbecovirus, the source clade for SARS-CoV and SARS-CoV-2, present a particularly poignant pandemic threat, due to the extraordinary viral genetic diversity represented among several sympatric species of their horseshoe bat hosts. To date, Sarbecovirus surveillance has been almost entirely restricted to China. More vigorous field research efforts tracking the circulation of Sarbecoviruses specifically and Betacoronaviruses more generally is needed across a broader global range if we are to avoid future repeats of the COVID-19 pandemic.

PCSK9 inhibition for LDL lowering and beyond – implications for patients with peripheral artery disease

VASA ◽  
2018 ◽  
Vol 47 (3) ◽  
pp. 165-176 ◽  
Author(s):  
Katrin Gebauer ◽  
Holger Reinecke
Keyword(s):  
Cardiovascular Risk ◽  
Risk Reduction ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Past Century ◽  
Pcsk9 Inhibitors ◽  
Cardiovascular Risk Reduction ◽  
Simultaneous Application ◽  
The Past ◽  
Pcsk9 Inhibition

Abstract. Low-density lipoprotein cholesterol (LDL-C) has been proven to be a causal factor of atherosclerosis and, along with other triggers like inflammation, the most frequent reason for peripheral arterial disease. Moreover, a linear correlation between LDL-C concentration and cardiovascular outcome in high-risk patients could be established during the past century. After the development of statins, numerous randomized trials have shown the superiority for LDL-C reduction and hence the decrease in cardiovascular outcomes including mortality. Over the past decades it became evident that more intense LDL-C lowering, by either the use of highly potent statin supplements or by additional cholesterol absorption inhibitor application, accounted for an even more profound cardiovascular risk reduction. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a serin protease with effect on the LDL receptor cycle leading to its degradation and therefore preventing continuing LDL-C clearance from the blood, is the target of a newly developed monoclonal antibody facilitating astounding LDL-C reduction far below to what has been set as target level by recent ESC/EAS guidelines in management of dyslipidaemias. Large randomized outcome trials including subjects with PAD so far have been able to prove significant and even more intense cardiovascular risk reduction via further LDL-C debasement on top of high-intensity statin medication. Another approach for LDL-C reduction is a silencing interfering RNA muting the translation of PCSK9 intracellularly. Moreover, PCSK9 concentrations are elevated in cells involved in plaque composition, so the potency of intracellular PCSK9 inhibition and therefore prevention or reversal of plaques may provide this mechanism of action on PCSK9 with additional beneficial effects on cells involved in plaque formation. Thus, simultaneous application of statins and PCSK9 inhibitors promise to reduce cardiovascular event burden by both LDL-C reduction and pleiotropic effects of both agents.

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