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The vaginal microbiome undergoes dramatic shifts before and throughout pregnancy. Although the genetic and environmental factors that regulate the vaginal microbiome have yet to be fully elucidated, high-throughput sequencing has provided an unprecedented opportunity to interrogate the vaginal microbiome as a potential source of next-generation therapeutics. Accumulating data demonstrates that vaginal health during pregnancy includes commensal bacteria such as Lactobacillus that serve to reduce pH and prevent pathogenic invasion. Vaginal microbes have been studied as contributors to several conditions occurring before and during pregnancy, and an emerging topic in women's health is finding ways to alter and restore the vaginal microbiome. Among these restorations, perhaps the most significant effect could be preterm labor (PTL) prevention. Since bacterial vaginosis (BV) is known to increase risk of PTL, and vaginal and oral probiotics are effective as supplemental treatments for BV prevention, a potential therapeutic benefit exists for pregnant women at risk of PTL. A new method of restoration, vaginal microbiome transplants (VMTs) involves transfer of one women's cervicovaginal secretions to another. New studies investigating recurrent BV will determine if VMTs can safely establish a healthy Lactobacillus -dominant vaginal microbiome. In most cases, caution must be taken in attributing a disease state and vaginal dysbiosis with a causal relationship, since the underlying reason for dysbiosis is usually unknown. This review focuses on the impact of vaginal microflora on maternal outcomes before and during pregnancy, including PTL, gestational diabetes, preeclampsia, and infertility. It then reviews the clinical evidence focused on vaginal restoration strategies, including VMTs., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Microbes and humans have been closely associated throughout evolution; this symbiotic and/or commensal relationship is crucial for normal development and health. The use of probiotics has been the topic of intense investigation in the past couple of decades because they have the capability to promote health. Based on these studies, it can be debated whether they are being used to promote overall health or to treat and prevent diseases. This review provides an overview and analysis of evidence about what is currently known about the health benefits of these agents that are marketed for use in children and neonates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

One of the most controversial areas in neonatology is whether probiotics should be provided routinely to preterm infants to prevent necrotizing enterocolitis (NEC). This review provides the reader with a brief overview of NEC and current concepts of its pathophysiology, discusses the microbial ecology of the intestine in preterm infants and factors that may lead to a "dysbiosis", summarizes studies of probiotics in preterm infants, elaborates on the need for regulation in this area, and discusses alternatives to probiotics and what is the future for the prevention of NEC., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The microbes in the human intestinal tract interact with the host to form a 'superorganism'. The functional aspects of the host microbe interactions are being increasingly scrutinized and it is becoming evident that this interaction in early life is critical for development of the immune system and metabolic function and aberrations may result in life-long health consequences. Evidence is suggesting that such interactions occur even before birth, where the microbes may be either beneficial or harmful, and possibly even triggering preterm birth. Mode of delivery, use of antibiotics, and other perturbations may have life-long consequences in terms of health and disease. Manipulating the microbiota by use of pro- and prebiotics may offer a means for maintenance of 'healthy' host microbe interactions, but over-exuberance in their use also has the potential to cause harm. Considerable controversy exists concerning the routine use of probiotics in the prevention of necrotizing enterocolitis. This chapter will provide a brief overview of the developing intestinal microbiome and discuss the use of pro- and prebiotics in preterm infants., (© 2014 S. Karger AG, Basel.)

The interplay between microorganisms and the intestine of newborn infants is associated with diverse functional and clinical outcomes that result from the specific interactions among microbial communities, their products, and the unique characteristics of the gastrointestinal tract. Multiple mechanisms of action for infant formula ingredients with probiotic activity appear to exist. These mechanisms are thought to protect the host not only from intestinal diseases but also from systemic infection. However, questions about the safety of probiotics for preterm infants remain unanswered, particularly with regard to sepsis, immunomodulatory effects, and microbial resistance. Few well-designed studies have been conducted to evaluate the effects of probiotic, prebiotic, and synbiotic ingredients on relevant clinical outcomes in preterm infants. Although existing data are encouraging, there is insufficient evidence to recommend the routine use of these ingredients in all preterm infants., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Purpose of Review: The increasing use of probiotics in neonates deserves scrutiny of the therapeutic as well as potentially harmful effects of these bacteria. In this review we describe the possible application of probiotics in the more common diseases in the neonatal period., Recent Findings: Recent advances in our capability to identify microbes and their function in the gastrointestinal tract offer exciting opportunities to discover the pathophysiology of enigmatic diseases such as necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in the neonate. The relationship of the resident intestinal microbes to neural and muscular processes such as intestinal motility and neurodevelopment are also being evaluated., Summary: We focus on the possibility of the application of probiotics for disorders of motility in the infant, NEC and LOS. Here we will summarize some of the recent advances in these areas as they relate to clinical practice and discuss areas where additional research is needed.

Necrotizing enterocolitis (NEC) is a devastating disease affecting primarily premature infants. Despite advances in neonatal care, the mortality rate following NEC has not changed significantly in the past 30 years. New preventative measures are needed. In this review, we will provide information to assess the possible role of probiotics, prebiotics and related agents in the prevention of this devastating disease. We will also discuss short and long term safety issues as well as potential alternatives. Although it is tempting to rebuild the intestinal microbiota using the agents such as pro and prebiotics during infancy, routine use is not yet warranted a cautious approach on the basis of sounds scientific data is needed.

An essential symbiotic relationship exists between intestinal cells and commensal bacteria within the human gastrointestinal tract. Alteration or absence of this interaction may play a role in the development of human disease. Use of probiotic organisms has yielded improvement of certain medical conditions, such as inflammatory and infectious gastrointestinal disease, although the mechanisms of benefit remain poorly defined. The administration of live organisms is not without risk, both potential and realized, particularly in certain populations. Therefore, it is of considerable interest to determine if the health benefits of probiotics can be attained without the risks associated with administration of a live organism. Reviewed here is the evidence that heat-killed, ultraviolet-inactivated, and even components of these agents may be just as effective and considerably safer for the host.

Lactobacillus rhamnosus GG (LGG), a probiotics, ameliorates intestinal and other organ inflammation in infant rats. The hypothesis is that live and heat-killed LGG have similar effects on decreasing the inflammatory response induced by E. coli lipopolysaccharide (LPS) in the infant rat. Using a gastrostomy-fed rat model, 7-d-old rat pups were gastrostomy fed with or without live LGG (10(8) or 10(12) cfu x L(-1) x kg(-1) x d(-1)) for 6 d. In a separate experiment, LPS was administered to rat pups with or without live or heat-killed LGG (10(8) cfu x L(-1) x kg(-1) x d(-1)). Cytokine/chemokine proteins were determined by ELISA or multiplex assay. Both live and heat-killed LGG decreased LPS-induced cytokine-induced neutrophil chemoattractant-1 (CINC-1) production in liver and plasma (p < 0.05) and also showed a trend (p = 0.09) in lungs. Live and heat-killed LGG ameliorated LPS-suppressed IL-10 level in lungs (p < 0.05). Both forms of LGG decreased IL-1b production in liver. There was no difference between low and high doses of live LGG in the production of CINC-1, TNF-alpha, and myeloperoxidase (MPO). There was a trend of increase of claudin-1 in both live and heat-killed groups (p = 0.08). In conclusion, both live and heat-killed LGG provided by the enteral route decrease LPS-induced proinflammatory mediators and increase anti-inflammatory mediators.

As we learn more about interactions between microbes and the developing gastrointestinal (GI) tract, it is becoming clear that the establishment of the intestinal "microbiome" shortly after birth plays a critical role in the early origins of health and disease. Nutrition, mode of delivery, the use of maternal or postnatal antibiotics, and pre- and probiotics are factors that may alter the microbial ecology and affect lifelong gene expression. Because the neonatal period is a critical period of development when microbes become established in the GI tract, the long-term effects of manipulations of the GI microbial ecology during this time are more amplified than the effects of later manipulations. In this paper, recent research findings are reviewed with the intent of providing information about the benefits of early manipulation of the GI microbiome, but also to give a warning about its indiscriminant manipulation during the perinatal and neonatal time periods.

During the course of mammalian evolution, there has been a close relationship between microbes residing in the gastrointestinal (GI) tract and the mammalian host. Although the host provides the microbes with a warm environment and nutrients, they, in turn, undergo various metabolic processes that aid the host. The host has developed weapons against microbes that are considered foreign, as well as mechanisms to tolerate and live synergistically with most of the microbes in the GI tract. This relationship is proving to be important not only in the neonatal period and during infancy, but it is becoming increasingly evident that microbial colonization in early life may affect the individual's health throughout life. Here we will review this relationship in terms of health and disease, with a focus on the aspects of this relationship during maturation of the host.

Objectives: A gastrostomy-fed rat infant "pup-in-a-cup" model was used to test the hypothesis that enterally administered Lactobacillus rhamnosus GG (LGG) decreases the proinflammatory response induced by Escherichia coli lipopolysaccharide (LPS) in the developing infant rat small intestine, plasma, lung and liver., Methods: Two groups of 6- to 7-day-old pups were fed a rat milk substitute with LPS added via the gastrostomy tube for 6 days. One of the rat milk substitute-fed groups received supplemental LGG; another group received LPS without LGG. Age-matched mother-fed rat pups were used as controls., Results: LPS treatment blunted body growth, but LGG supplementation had no effect on weight increments. LGG decreased LPS-induced inflammation in intestinal tissue; CINC-1 (rodent IL-8 equivalent) production in plasma, liver, lung and distal small intestine; and tumor necrosis factor alpha (TNF-alpha) production in plasma and lung. Cytokine multiplex assay showed lung interleukin (IL)-1beta, IL-6, IL-10, IL-18, growth-related oncogene (GRO)/KC (rat CINC-1) and TNF-alpha were significantly higher in gastrostomy-fed, LPS-treated pups than in mother-reared pups, and LGG significantly blunted the LPS-induced elevation of IL-1beta, IL-10, IL-18, GRO/KC and TNF-alpha; liver GRO/KC was significantly higher in gastrostomy-fed, LPS-treated pups than in mother-reared pups, and LGG significantly blunted the LPS-induced elevation of GRO/KC., Conclusions: LGG provided by the enteral route is able to downregulate LPS-induced proinflammatory mediators. This effect is not only present in the splanchnic organs, that is, the intestine and the liver, but extends to the plasma and a distal organ, the lung.

Certain probiotic bacteria show anti-inflammatory activity after being heat killed, whereas others do not, suggesting that the gastrointestinal environment may alter the activity of probiotic bacteria. Occasionally, probiotics are provided when a patient is also being treated with oral antibiotics; this may have an effect on the probiotic activity. We hypothesized that Lactobacillus rhamnosus GG (LGG) are capable of downregulating tumor necrosis factor-alpha (TNFalpha)-induced interleukin (IL)-8 production under all 3 of these conditions, and that LGG act through the nuclear factor kappaB (NFkappaB)/inhibitor of kappaB (IkappaB) pathway. Caco-2 cells were treated with live or heat-killed LGG in doses ranging from 10(4) to 10(10) cfu/L, in the presence or absence of antibiotics and TNFalpha in the media. TNFalpha-induced production of IL-8 by Caco-2 cells was modulated by LGG under all 3 conditions. However, higher doses of live LGG without TNFalpha in the presence or absence of antibiotics in vitro induced the production of IL-8 (P = 0.001). Heat-killed LGG also blunted the TNFalpha-induced IL-8 production (P < 0.01), but by itself did not increase IL-8 production at higher doses as markedly as live LGG (P < 0.05). LGG reduced the TNFalpha-induced NFkappaB translocation to the nucleus and lessened the decrease in IkappaB in the cytoplasm (P < 0.05). LGG reduced TNFalpha-induced IL-8 production by affecting the NFkappaB/IkappaB pathway in Caco-2 cells. High doses of live LGG markedly increased IL-8 production, but heat-killed LGG caused only a slight increase in IL-8. Thus, heat-killed LGG may effectively ameliorate inflammation with a lower potential than live LGG at high doses to cause inflammation.

Probiotics are widely used in the treatment and prevention of gastrointestinal problems. However, in some immune- compromised populations, the administration of live microorganisms may not be appropriate. A potential alternative to live microorganisms is to inactivate them as long as the beneficial function is retained. We hypothesized that UV-inactivated Lactobacillus rhamnosus GG (LGG) could downregulate interleukin-8 (IL-8) production in intestinal epithelial cells stimulated by the pathogenic ligand, flagellin, using similar mechanisms as live LGG. Caco-2 cells were pretreated with live or UV- inactivated LGG at 1011 colony-forming units/L and stimulated by flagellin at a dose of 500 μg/L. lL-8 production was measured by ELISA, inhibitor of κB (IκB) and ubiquitinated-lκB (Ub-lκB) expression by immunoblotting and nuclear factor (NF) κB localization by immunofluorescence staining. Flagellin induced a 17-fold increase in lL-8 production compared with control (P < 0.05), whereas pretreatment with either live LGG or UV-inactivated LGG resulted in 66 and 59% decreases, respectively, compared with the flagellin group(P< 0.05). Flagellin-induced NFκB nuclear translocation was prevented by both live and UV-inactivated LGG. Flagellin decreased IκB, which was reversed by either live or UV-inactivated LGG (P < 0.05). UV-inactivated LGG decreased Ub-lκB expression (P < 0.051, although live LGG had no effect. This study supports the concept that UV-inactivated and live LGG are equally effective in decreasing lL-8 production in the intestinal epithelium. Although the mechanism involves different pathways, both alter cytoplasmic IκB, thereby inhibiting NFκB nuclear translocation. [ABSTRACT FROM AUTHOR]

The maternal microbiome has emerged as an important area of investigation. While birth is a critical timepoint for initial colonization of the newborn, the fetus resides in the womb surrounded by multiple unique colonized niches. The maternal microbiome has recently been shown to be associated with several morbidities in offspring. Understanding the multiple bacterial niches within the pregnant woman and how they interact with the fetus in-utero can lead to novel therapies to improve the health of offspring. In this review, we provide an overview of the available literature on normal bacterial colonization within the individual niches of the pregnant woman and the known associations with outcomes in offspring, including a discussion of the controversy of in-utero colonization. [ABSTRACT FROM AUTHOR]