Faculty Opinions recommendation of 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. 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.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzz048.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.

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

FEMS Microbiology Reviews ◽

10.1093/femsre/fuab011 ◽

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.

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

Microorganisms ◽

10.3390/microorganisms9030555 ◽

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.

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The zoonotic potential of bat-borne coronaviruses

Emerging Topics in Life Sciences ◽

10.1042/etls20200097 ◽

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.

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

VASA ◽

10.1024/0301-1526/a000689 ◽

2018 ◽

Vol 47 (3) ◽

pp. 165-176 ◽

Cited By ~ 4

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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Archaeology in the Past Century

Scientific American ◽

10.1038/scientificamerican02021901-20976supp ◽

1901 ◽

Vol 51 (1309supp) ◽

pp. 20976-20977

Author(s):

W. M. Flinders Petrje

Keyword(s):

Past Century ◽

The Past

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Catholicism and Cosmopolitanism: the Confluence of Three Catholic Scholars and the Cosmopolitan Democrats on State Sovereignty and the Future of Global Governance

De Ethica A Journal of Philosophical Theological and Applied Ethics ◽

10.3384/de-ethica.2001-8819.163237 ◽

2016 ◽

Vol 3 (2) ◽

pp. 37-51

Author(s):

Matthew Bagot

Keyword(s):

Global Governance ◽

State Sovereignty ◽

Current Debate ◽

Past Century ◽

Jacques Maritain ◽

The Past ◽

Technological Advances ◽

The Future ◽

Cosmopolitan Democracy ◽

Catholic Tradition

One of the central questions in international relations today is how we should conceive of state sovereignty. The notion of sovereignty—’supreme authority within a territory’, as Daniel Philpott defines it—emerged after the Treaty of Westphalia in 1648 as a result of which the late medieval crisis of pluralism was settled. But recent changes in the international order, such as technological advances that have spurred globalization and the emerging norm of the Responsibility to Protect, have cast the notion of sovereignty into an unclear light. The purpose of this paper is to contribute to the current debate regarding sovereignty by exploring two schools of thought on the matter: first, three Catholic scholars from the past century—Luigi Sturzo, Jacques Maritain, and John Courtney Murray, S.J.—taken as representative of Catholic tradition; second, a number of contemporary political theorists of cosmopolitan democracy. The paper argues that there is a confluence between the Catholic thinkers and the cosmopolitan democrats regarding their understanding of state sovereignty and that, taken together, the two schools have much to contribute not only to our current understanding of sovereignty, but also to the future of global governance.

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Aftershocks

10.23943/princeton/9780691172330.001.0001 ◽

2017 ◽

Cited By ~ 1

Author(s):

Seva Gunitsky

Keyword(s):

Twentieth Century ◽

Regime Change ◽

International System ◽

Political Legitimacy ◽

Great Powers ◽

Past Century ◽

The Past ◽

Sudden Rise ◽

The World ◽

National Borders

Over the past century, democracy spread around the world in turbulent bursts of change, sweeping across national borders in dramatic cascades of revolution and reform. This book offers a new global-oriented explanation for this wavelike spread and retreat—not only of democracy but also of its twentieth-century rivals, fascism, and communism. The book argues that waves of regime change are driven by the aftermath of cataclysmic disruptions to the international system. These hegemonic shocks, marked by the sudden rise and fall of great powers, have been essential and often-neglected drivers of domestic transformations. Though rare and fleeting, they not only repeatedly alter the global hierarchy of powerful states but also create unique and powerful opportunities for sweeping national reforms—by triggering military impositions, swiftly changing the incentives of domestic actors, or transforming the basis of political legitimacy itself. As a result, the evolution of modern regimes cannot be fully understood without examining the consequences of clashes between great powers, which repeatedly—and often unsuccessfully—sought to cajole, inspire, and intimidate other states into joining their camps.

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Variable oil and argumentative conflict in the Middle East

Tikrit Journal For Political Science ◽

10.25130/poltic.v0i0.222 ◽

2020 ◽

pp. 824

Author(s):

Malik Daham Mata’ab

Keyword(s):

Middle East ◽

Past Century ◽

Large Area ◽

The Past ◽

The World

Oil has formed since its discovery so far one of the main causes of global conflict, has occupied this energy map a large area of conflict the world over the past century, and certainly this matter will continue for the next period in our century..

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