1. Introduction
1.1. Gut microbiota, health and diseases
In humans there are a multitude of site-specific communities of bacteria localized on the skin, mucosal surfaces, and in the intestinal tract [1,2]. The total number of prokaryotic cells is estimated to be around 1014, ten times more than the number of eukaryotic cells. These microbial communities interact extensively with the host, a process which is crucial for host development and homeostasis. Most of the microbiota is located in the gastrointestinal (GI) tract, and progressively increase in number from the jejunum to the colon. In the colon, the levels of bacteria are as high as 1011 microorganisms per gram of luminal content with a very wide diversity. The composition of gut microbial communities was originally known through culture-based studies, which estimated that 400 to 500 different species are present in the adult human intestinal tract [3]. Through the most recent culture-independent analyses, gut microbiota is thought to comprise up to 1000 bacterial species per individual and over 5000 species in total [4]. The gut microbiota is dominated by only four phyla, i.e. Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria, although there are more than 50 bacterial phyla on Earth [1].
Although the gut microbiota community was mostly studied in terms of pathogenic relationships for several decades, it is now recognized that most microorganism-host interactions in the gut are, in fact, commensal or even mutualistic [1,2]. This complex ecosystem has many functions which contribute to major roles for the host, including metabolic functions, barrier effects, and maturation of the immune system [5,6]. Indeed, bacterial colonic fermentation of non-digestible dietary residues and endogenous mucus is an important metabolic process in humans. The metabolites produced by this bacterial fermentation are mostly short-chain fatty acids (SCFAs) which supply energy and nutritive products to the bacteria, and trophic functions on the intestinal epithelium [7]. However, bacterial fermentation of proteins and peptides can also generate potentially pathogenic metabolites, such as phenol, amines, indols, and thiols [8]. The barrier effect refers to a resistance to colonization by exogenous or opportunistic bacteria that are at a low level in the gut [9]. Many mechanisms are thought to be responsible for this effect, including secretion of antimicrobial molecules, competition for nutrients, and attachment to ecological niches. These mechanisms also contribute to maintaining equilibrium in the microbial population of the gut. Finally, the gut microbial community has a major immune function [10].The intestinal immune system is separated from the gut microbiota by a single epithelial layer, which allows cross-talk between bacteria and the host. The commensal gut microbiota therefore profoundly influences the development of the intestinal adaptative immune system, being crucial for the development of gastrointestinal lymphoid tissue (GALT), homeostasis between T-helper 1 (Th1) and T-helper 2 (Th2) cell activity, as well as the acquisition of oral tolerance [10].
As the gut microbiota is greatly involved in the intestinal homeostasis, any dysbiosis could lead to dysfunctions. Hence, several diseases have been associated with alterations in the composition of the gut microbiota such as inflammatory bowel diseases (IBD) [11,12], irritable bowel syndrome (IBS) [13], and allergic diseases [14].
As IBD is concerned, although a direct pathogenic role for a specific agent has not been shown, there is evidence that autochthonous intestinal microbiota is involved (for review, see [15]). Several studies through culture-dependent and –independent analyses have reported differences in microbiota in patients suffering from IBD compared to healthy ones with less diversity in fecal microbiota [11] and higher numbers of mucosa-associated bacteria [16] in IBD patients. Indeed, IBD patients have fewer bacteria with anti-inflammatory properties and/or more bacteria with proinflammatory properties [15]. Likewise, some clinical studies reported differences in the composition of bacterial communities compared to period without allergic symptoms [17,18].
Irritable bowel syndrome (IBS) is defined by functional recurrent abdominal pain associated with abdominal distension and changes in bowel habits (constipation, diarrhea, or both). The etiology remains elusive; however, there is growing evidence of the role of gut microbiota in IBS [19].
Some recent studies have also suggested that obese individuals have a higher abundance of
Lastly, antibiotic courses have been shown to impact the microbiota with long term alterations [27,28]. Few studies investigated the health consequences of such alterations, but for
These associations need to be confirmed in large studies. Moreover, it is still unclear whether the altered microbiota composition is a consequence rather than a cause of these disorders. Moreover, microbiota could promote disease in genetically susceptible hosts. Nevertheless, studies conducted to identify relationships between gut microbiota and diseases are a prerequisite to new approaches of therapeutics.
2. Probiotics, prebiotics, tools for modulating the gut microbiota
The associations of gut microbiota and diseases have given rise to the interest in manipulating gut microbiota as a new means of prevention or therapy. Indeed, some bacteria, mainly bifidobacteria and lactobacilli, have for a long time been thought to have beneficial health effects. They were firstly described by a few visionary scientists like Metchnikoff, Nissle, and Shirota about a century ago. This concept of “useful microbes” as written by Metchnikoff in his publication “On the prolongation of life” in 1907 [30] has led many years later to the use of “probiotic” strains to deliberately manipulate the microbiota. This concept has been forgotten during the expansion of the era of antibiotics and vaccines. However, research on the roles of the commensal microbiota gave a renewed interest for these beneficial microorganisms. Currently, probiotics are defined as “live microorganisms which when administered in adequate amounts confer a health benefit on the host” [31,32]. The most widely used probiotics include lactic acid bacteria, specifically
Their beneficial effects could be through the production of metabolites, such as short chain fatty acids or other small molecules, or the bacterial components, such as DNA or peptidoglycan. However, these effects are strain-specific and further work is still required to confirm their benefits to health.
Modulation of the gut microbiota can be also achieved by the use of prebiotics. Prebiotics are defined as non-digestible dietary components that beneficially affects the host by selectively stimulating the growth and/or the activity of one or a limited number of bacteria in the colon, and thus improves host health [37]. They are mainly oligosaccharides, and bacteria mainly enhanced are bifidobacteria. Their potential interest lies in the fact that their effect is linked to a modification of the equilibrium of the autochthonous gut microbiota and not to a single or a limited number of exogenous strain(s) as for probiotics. Moreover, in terms of safety, they have not the side effect of probiotic supplementation, for which systemic translocation of the ingested live bacteria has been reported in some cases during probiotic uses [38]. Prebiotic supplementation has been less studied than probiotic supplementation. Although prebiotic supplementation leads constantly to an increase in gut bifidobacteria levels, their effects in terms of health benefits of an early use of infant formula enriched with prebiotics appear with limited or unclear clinical significances [39]. Thus, the Committee on Nutrition of the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) did not recommend the routine use of prebiotic-supplemented formula [39]. However, no adverse effects have been observed.
The increase use of association of probiotics and prebiotics, named “synbiotic” is appealing. However, a very limited number of such supplementation has been studied in infants. An alternative option is the use formulas fermented with lactic acid-producing bacteria during the production process that are subsequently inactivated by heat or other means at the end of the process [40]. This leads to a probiotic/prebiotic activity likely related to both production of active bacterial metabolites such as transoligosaccharides and presence of bacterial components such as cell membrane and DNA [41,42]. The limited number of studies on this kind of formula does not allow general conclusions to be drawn on the use and effects of fermented formulae [40]. It is recommended that the observed effects should be assessed in further randomized controlled trials.
Both uses of prebiotics and synbiotics in neonates are not included in the present review.
3. Gut bacterial establishment
The formation of the intestinal ecosystem starts rapidly during the neonatal stage of life (see [43,44] for review). Colonizing bacteria originate mainly from the mother; the gut microbiota is a major source. Other sources include the microbiota of the vagina, perineum, skin, and even breast milk [45,46]. The first colonizing bacteria are facultative anaerobes due to the abundance of oxygen in the gut. This decreases the redox potential in the gut lumen, creating a reduced environment that favors the establishment of obligate anaerobes [43]. However, little is known about the factors that lead to the establishment of specific bacterial strains. Then, during the infant stage of life, numerous bacteria are encountered in the environment including the skin microbiota of parents, siblings, nurses, and foods. Hence, over time, successively larger numbers of bacteria are established in the infant gut, and these are mainly comprised of obligate anaerobes. This leads to a high interindividual variability in the composition and patterns of bacterial colonization during the first weeks of life. By the end of the first year of life, the gut bacterial composition converges toward an adult-like microbiota profile [47].
Various external factors can affect the pattern of bacterial colonization, i.e. mode of delivery, mode of infant feeding, and environment [43,44]. Infants born by cesarean section are deprived of contact with their mother’s gut and vaginal microbiota, which decreases bacterial diversity and colonization by obligate anaerobes such as bifidobacteria and
4. Gut microbiota and pediatric diseases: a rational for probiotic use in neonates
The early bacterial pattern in the first weeks of life appears to be a crucial step in the establishment of the various functions of the gut microbiota. In fact, recognition of self– and non–self–antigens begins early in life, perhaps even
Late-onset diseases could be therefore associated with an impairment of this step, all the more as early impairment in bacterial establishment can have long term effects in terms of bacterial pattern [58] as well as in terms of immune maturation [49,59]. Indeed, a large number of studies have shown that an imbalance of the numbers of Th1 and Th2 cells may be at the origin of a great variety of disease processes.
The first disease associated to this imbalance is allergy. Thus, the initial composition of the infant gut microbiota may be a key determinant in the development of atopic disease [60]. This hypothesis is consistent with the delayed colonization of the digestive tract associated with changes in lifestyle over the last 15 years in Western countries [43,44], where incidence of allergic diseases had sharply increased since a decade. Moreover, factors known to modify establishment of the gut microbiota, e.g. birth through caesarian section [61,62], prematurity [63], and exposure to antibiotics during pregnancy [64] have been associated with a higher risk of atopic disease. This hygiene hypothesis implicating a relationship between allergic diseases and gut microbiota is supported by several clinical studies which reported differences in the composition of the fecal microbiota between infants who live in countries with high or low prevalence of allergy, as well between infants with or without allergic diseases. In fact, several reports have associated allergic diseases with abnormal bacterial pattern. Low diversity [65] and low levels of bifidobacteria have been associated with allergy development [66,67], as well as high levels of clostridia [14,66]. A recent study revealed differences in the abundance of
Likewise, early alterations in the gut microbiota have been linked with the risk of later overweight or obesity associated with lower levels of bifidobacteria and higher levels of
For many years, a number of studies have documented differences between patients suffering from inflammatory bowel diseases and healthy persons, even if there is still debate about whether changes precede or follow the development of IBD [70]. For instance, a decreased prevalence of dominant members of the human commensal microbiota, i.e.
Lastly, associations between intestinal microbiota and autism have been reported such as the overgrowth of neurotoxin-producing clostridia [76]. Several reports indicate that certain clusters of clostridia are present in higher levels in fecal microbiota from autistic infants [77,78]. Overgrowth of
Hence, although a causal relationship has not been categorically established, there is emerging evidence that the initial gut bacterial colonization during the first weeks of life is of great importance for infant health. Perinatal determinants altering the colonization pattern could therefore lead to a higher risk of later diseases. For instance, as already mentioned, infants born through cesarean section and therefore colonized by an altered bacterial pattern as compared with vaginally delivered ones have been reported to be at higher risk of either allergic diseases [80-82], or celiac disease [83], or obesity [84-86], or type 1 diabetes [87]. A prolonged breast-feeding over one year has been linked to a lower risk of overweight or obesity [88]. Likewise, changes in the establishment of gut microbiota observed in modern Western infants result in reduced bacterial exposure [43,44]. Thus, these infants lack of adequate bacterial stimuli, leading to a deviated maturation of their immune system likely responsible for a higher risk of allergic disease development or inflammatory bowel diseases [56].
5. Probiotics in fullterm neonates
The potential benefits of the use of probiotics in pediatrics have been recently reviewed [89,90]. It mainly includes treatment acute viral gastroenteritis [91], prevention of antibiotic-associated diarrhea [92,93], reduction of the inflammatory response in IBD patients [11]. Limited effects have been observed in colicky infants [94]. However, a recent study reported a clear improvement of the symptoms of colic within one week of
Given the likely link between the early bacterial pattern and later health status reported, a very early administration of probiotics when the gut microbiota is not fully established is of great interest and we have focused this review on this approach. Many attempts of early probiotic supplementation have been made for a long time, and numerous studies related to the use of infant formula supplemented with probiotics strains have been recently published [39]. This early use is reported to have some beneficial effects in terms of prevention of late development of some diseases. Administration is often given soon after birth, and the duration is variable according to the study, but often prolonged over several weeks or months. Lastly, dosages varied, ranging from 106 to ~109 CFU/mL or/g. The most frequently studied probiotic strains were
Some studies have included the effects of such supplementation on growth. However, no significant effects have been shown on growth, but without any negative results [39]. Likewise, no reduction of gastrointestinal or respiratory infections, or reduction of antibiotic use have been reported, but a limited number of studies investigated such effect, avoiding to drawn final conclusions. Moreover, one difficulty to assess the health-promoting effects lies in the fact that the probiotics properties are strain-dependent and the use of different strains could explain the discrepancies between the observed effects. Second, mechanism(s) of action of the probiotics is not always well-established. Probiotics can have health-promoting effects related to their interaction with the gut microbiota, the barrier functions and the immune system. In particular, probiotic supplementations were shown to impact the intestinal maturation as reported with
The prevention of allergy through such early administration of probiotics is appealing. Though evidence of their effect is conflicting, their administration to infants at high risk for atopy and/or to their mothers seems to be effective for preventing infants from developing atopic disease [101,102]. Four studies investigated probiotic supplementation begun during pregnancy. Administration of
These data led the Nutrition Committee of ESPGHAN to conclude that there is too much uncertainty to draw reliable conclusions [39], confirmed through a recent review [112]. However, the Cochrane Database of Systematic Reviews claimed that there is a possible role a probiotics intervention in prevention of atopic dermatitis [113]. These promising results associated to the fact that the impact on the immune system has been shown to be strain-dependant [114] highlighting the importance of the choice of the probiotic strain argue for further studies in this field.
Identifying through animal studies and clinical studies a possible link between gut microbiota and obesity [69,84,86] may offer promising strategies through the gut modulation to prevent obesity. The intestinal microbiota may contribute to the development of inflammation and insulin resistance leading to overweight or obesity, either by its role in the regulation of energy homeostasis and fat storage or by the chronic inflammation it could induce, or both [21,115]. Reducing the susceptibility to obesity by early probiotics intervention would be a useful adjunct in strategies to alleviate the huge burden of childhood obesity which can be a risk factor for later diseases such as type 2 diabetes, hypertension and coronary heart disease [116]. The findings of early differences in microbiota of infants who later become overweight or obese [69] argues for an early intervention. Likewise, differences in obese and non obese children has been found [117,118]
Up to now, only one study on the effects on obesity of early probiotics supplementation has been conducted [119]. Pregnant women (n=159) were randomized and double-blinded to receive
6. Probiotics in preterm neonates
6.1. Gut bacterial establishment in preterm neonates
The current more obvious interest of probiotics use in neonates is very likely for preterm infants. In fact, preterm infants, and particularly those who are born at a low or very low gestational age and/or birth weight experience a delayed and abnormal pattern of gut colonization, particularly with regard to bifidobacteria and lactobacilli, normally dominant in healthy full term infants. The first studies on the gut bacterial colonization in preterm infants, based on culture methods and performed in the 80s, described a delayed colonization by many of the bacteria found in healthy fullterm infants [121-123]. However, more recent studies reported a greater delay either by culture [124-126] or culture-independent methods [50,124,126-130]. Recently, the use of a pyrosequencing-based method confirmed this aberrant pattern in low and very low birth weight infants [52].
The predominant facultative bacterial species in the fecal microbiota of preterm infants undergoing intensive care are staphylococci. Enterobacteria (mainly
This bacterial establishment is the expression of colonization from the environment rather from maternal origin. A combination of more frequent birth through cesarean section, large antibiotic use, delayed initiation of enteral feedings, and exposure to the unusual microorganisms that populate the neonatal intensive care units may explain this abnormal pattern of colonization.
This impaired intestinal colonization may predispose preterm infants to diseases. Indeed, they are at high risk to acquire recurrent bacterial infections during their first weeks of life. Both the permanent exposure to microorganisms due to frequent invasive procedures and the immaturity of the newborn immune system are responsible for the increased susceptibility to severe nosocomial infections. Early-onset sepsis remain an important cause among very preterm infants [132], thought to be due – at least partly – to the gut microbiota, Gram negative bacilli being the most frequent bacteria encountered in sepsis by contrast with fullterm infants [132]. Recent studies have demonstrated the origin of gut bacteria in these infections [133,134]. Besides, necrotizing enterocolitis (NEC) remains an important cause of morbidity and mortality among very preterm infants. Despite many investigations, its pathogenesis remains unclear [135]. The hypothesis that intestinal microbes are necessary for the development of NEC is supported by several lines of evidence [136]. No specific bacteria or bacterial pattern has been causally associated with the development of NEC although bacterial colonization is recognized as an important factor [137-139]. Implication of bacteria is thought to be due to fermentation of non-hydrolyzed lactose, a consequence of the immaturity of the intestinal lactasic equipment in preterm infants [140-142]. The genus
Lastly, the very abnormal pattern observed particularly in VLBW infants could lead to an abnormal maturation of the functions of the intestinal ecosystem. Indeed, it could be a factor to develop late-onset disease such as allergy, obesity, such as suggested with a higher risk of allergy in infants born with a very low birth weight (VLBW)[63].
6.2. Probiotics in preterm neonates
Feeding oral probiotic bacteria may be therefore an effective way to change the abnormal pattern of colonization of preterm infants, and to have the potential to prevent the occurrence of gastrointestinal disorders in preterm infants. A relatively small number of trials have studied the effects of probiotics in those preterm infants. However, numerous meta-analyses or reviews (with a higher number than clinical trials, highlighting the great interest in this approach) have shown the potential benefits of such supplementation, leading to a significant and somewhat impressive reduction of all-cause mortality and NEC by more than half [146-148]. As for an example, the metaanalyse from the Cochrane Collaboration included 16 studies with 1371 infants treated with probiotics and 1376 controls [146]. Various probiotic strains have been used, i.e. lactobacilli, bifidobacteria or a combination of 2 or 3 strains. The most frequent
Other beneficial effects have been reported as a shortened time to full feeds. By contrast, if there is a trend toward a reduction of nosocomial sepsis, it does not reach the significance.
These beneficial effects are less obvious in extremely preterm infants, born with a very low birthweight (1000g or less, VLBW infants) [146]. This could be related with the fact that the probability to be colonized by probiotic strains diminished with decreasing birth weight [126]. Hence, in this latter study the improvement of gastrointestinal tolerance to enteral feeding was only reported in infants born with a birthweight >1000g. As infants weighting 1000g or less received antibiotic treatment more frequently, and had more frequent interruptions of enteral feeding than did infants weighing more than 1,000g, these findings suggest that these factors could prevent gut colonization by the probiotic strains, and, consequently, the capacity of probiotics to enhance intestinal function in extremely low birth weight infants [126].
Conclusions of the numerous reviews and metaanalyses strongly suggest that the use of probiotics in preterm infants could prevent tens of thousands of deaths annually. Hence, some authors recommend that it is time to change practice and to adopt the use of probiotics as a standard care in preterm infants [146,150]. However, controversies have emerged because there are yet too many unknowns about probiotics use [151,152]. One aspect concerns the safety although no negative effects have been reported even in long term follow-up [153]. However, data on this latter aspect are very scarce. Infrequent, systemic translocation of probiotics has been reported [38,154] raising some concerns about this side effect in the high-risk groups of low and very low birth weight infants who are characterized by high intestinal permeability, making this potential powerful tool a double-edge weapon. Increased incidence of NEC following probiotic administration has been observed in a preterm piglet model, may be related to the specific strain, dose, and the very immature gut immune system.[155]. A study in a pediatric unit even reported a trend toward an increase in nosocomial throughout a probiotic supplementation [156] although a routinary supplementation of VLBW infants with a probiotics strains over a 6-year period was safe [157].
To conclude, although there is encouraging data for the use of probiotics in particular in terms of NEC prevention, it may be reasonable to stand back from a routine use of probiotics in preterm infants. As suggested by several authors, probiotics supplementation should be a local decision [158-161]. Several questions have been raised. What is the interest of probiotic supplementation in units with low incidence of NEC? What are the mechanisms of action, which are not elucidated, in particular due to the lack of gut microbiota analyses in most of the studies? What are the beneficial effects apart reduction of incidence and severity of NEC, in particular concerning sepsis, since some results are promising, but large clinical trials are needed, as the ongoing study in Australia and New Zealand [162]. What is the safety of the various strains? Which product(s) should be administered, at what dose, when, and for how long [163]? Lastly, no general recommendation can be done currently for the special group of the VLBW infants regarding the lack of benefits of probiotics supplementation [146,160]. Further studies are thus recommended in this target population.
Lastly, no study had investigated the potential beneficial long-term effect of an early probiotics supplementation in terms of reduction of the risk of late-onset disease linked to an early dysbiosis such allergy and obesity for instance.
The Committee on Nutrition of ESPGHAN concluded – in a commentary published in 2010 – that there is not enough available evidence for a routine use of probiotics in preterm infants [164]. However, faced to some evidence of benefits of probiotics in preterm infants, guidelines have been proposed aiming at optimizing their use, emphasing that “routine” use does not equate “blind” use of probiotics, and raising the necessity to continue research in this field to provide answers to the current gaps [159].
7. Conclusion
The notion of “gut health” has become more and more popular. Currently, it is recognized that the gut microbiota contributes to the host health not only by assuming digestion and absorption of nutriments, but also by maturation of the immune system, defense against infection, signaling to the brain…
This leads to not only study the gut microbiota communities in terms of pathogenic relationships, as it was done for several decades, but also to study the endogenous microbiota and to investigate microorganism-host interactions in the gut that are, in fact, commensal or even mutualistic. Hence, currently several disease, which clinical symptom can be late in the life, are linked to dysbiosis that often occurred in the early step of gut colonization.
We need to learn more about the composition and functions of the gut microbiota and to the concept of early modulation of this microbiota. Thus, we are currently at the beginning of the era of probiotics which aim at counteracting deleterious effect of microorganisms with probiotics instead of using vaccines and antibiotics. This new field of medical microbiology is appealing and fascinating.
The current review aimed at giving the rational of the use of probiotics for promotion of health and prevention of disease through their use early in life when the gut microbiota is not fully established.
Several applications are claimed among them, some are appealing such as prevention of allergy. However, up to now, there are not enough data to recommend their routine use. But the potential interest in this field argues to do further research to validate the current beneficial results observed.
The most clear potential interest of early probiotic supplementation lies in taking care of preterm neonates, who are often colonized by an aberrant microbiota leading to high risks of early or late-onset of disease. Probiotic supplementation has been demonstrated to have benefits in terms of prevention of NEC. However, too many questions remain unanswered to recommend their routine use. One major concern is the safety linked to the ingestion of live microorganisms by an immature host. Hence, once again further research is needed in this exiting field with potential of health benefits.
References
- 1.
Dethlefsen L. Mc Fall-Ngai M. Relman D. A. An ecological and evolutionary perspective on human-microbe mutualism and disease. 2007 811 EOF 8 EOF - 2.
Bik EM. Composition and function of the human-associated microbiota Nutr Rev2009 Suppl 2:S164 S171. - 3.
The commensal microbiology of the gastrointestinal tract. Adv Exp Med BiolManson J. M. Rauch M. MS Gilmore 2008 - 4.
Zoetendal E. G. Rajilic-Stojanovic M. De Vos W. M. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota Gut2008 1605 EOF 1615 EOF - 5.
Fujimura KE, Slusher NA, Cabana MD, Lynch SV. Role of the gut microbiota in defining human health Expert Rev Anti Infect Ther2010 435 EOF 454 EOF - 6.
Sekirov I. Russell S. L. Antunes L. C. Finlay B. B. Gut microbiota in health and disease Physiol Rev2010 859 EOF 904 EOF - 7.
Wong JM, de SR, Kendall CW, Emam A, Jenkins DJ. Colonic health: fermentation and short chain fatty acids. J Clin Gastroenterol 2006,40:235-243. - 8.
Blachier F. Mariotti F. Huneau J. F. Tome D. Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences 2007 547 EOF 562 EOF - 9.
Stecher B. Hardt W. D. The role of microbiota in infectious disease Trends Microbiol2008 107 EOF 114 EOF - 10.
Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease Nat Rev Immunol2009 - 11.
Sartor RB. Microbial influences in inflammatory bowel diseases 2008 577 EOF 594 EOF - 12.
Reiff C, Kelly D. Inflammatory bowel disease, gut bacteria and probiotic therapy. Int J Med Microbiol 2010,300:25-33. - 13.
Collins S. M. Denou E. Verdu E. F. Bercik P. The putative role of the intestinal microbiota in the irritable bowel syndrome Dig Liver Dis2009 850 EOF 853 EOF - 14.
Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. GutPenders J. Thijs C. van den Brandt. P. A. Kummeling I. Snijders B. Stelma F. Adams H. van Stobberingh R. R. EE 2007 - 15.
Chassaing B. Darfeuille-Michaud A. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases 2011 1720 EOF 1728 EOF - 16.
Nishikawa J. Kudo T. Sakata S. Benno Y. Sugiyama T. Diversity of mucosa-associated microbiota in active and inactive ulcerative colitis. Scand J Gastroenterol2009 180 EOF 6 EOF - 17.
Ouwehand A. C. Nermes M. Collado M. C. Rautonen N. Salminen S. Isolauri E. Specific probiotics alleviate allergic rhinitis during the birch pollen season World J Gastroenterol2009 - 18.
Odamaki T. Xiao J. Z. Iwabuchi N. Sakamoto M. Takahashi N. Kondo S. Miyaji K. Iwatsuki K. Togashi H. Enomoto T. Benno Y. Influence of Bifidobacterium longum BB536 intake on faecal microbiota in individuals with Japanese cedar pollinosis during the pollen season. J Med Microbiol2007 1301 EOF 8 EOF - 19.
Dahlqvist G, Piessevaux H. Irritable bowel syndrome: the role of the intestinal microbiota, pathogenesis and therapeutic targets. Acta Gastroenterol Belg 2011,74:375-380. - 20.
Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature 2006,444:1022-1023. - 21.
Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care 2010,33:2277-2284. - 22.
Zhang H, DiBaise JK, Zuccolo A, Kudrna D, Braidotti M, Yu Y, Parameswaran P, Crowell MD, Wing R, Rittmann BE, Krajmalnik-Brown R. Human gut microbiota in obesity and after gastric bypass. Proc Natl Acad Sci U S A 2009,106:2365-2370 - 23.
Wu X. Ma Han C. Nawaz L. Gao M. Zhang F. Yu X. Zhao P. Li C. Zhou L. Wang A. Moore J. Millar J. E. Xu B. C. J. Molecular characterisation of the faecal microbiota in patients with type II diabetes Curr Microbiol2010 69 EOF 78 EOF - 24.
Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS OneLarsen N. Vogensen F. K. van den Berg. F. W. DS Nielsen Andreasen. AS Pedersen B. K. Al-Soud W. A. Sorensen S. J. Hansen L. H. Jakobsen M. 2010 e9085. - 25.
Duncan S. H. Lobley G. E. Holtrop G. Ince J. Johnstone A. M. Louis P. Flint H. J. Human colonic microbiota associated with diet, obesity and weight loss Int J Obes (Lond)2008 1720 EOF 1724 EOF - 26.
Brugman S. Klatter F. A. Visser J. T. Wildeboer-Veloo A. C. Harmsen H. J. Rozing J. Bos N. A. Antibiotic treatment partially protects against type 1 diabetes in the Bio-Breeding diabetes-prone rat. Is the gut flora involved in the development of type 1 diabetes? 2006 2105 EOF 2108 EOF - 27.
Resilience of the dominant human fecal microbiota upon short-course antibiotic challenge. J Clin MicrobiolDe La Cochetiere M. F. Durand T. Lepage P. Bourreille A. Galmiche J. P. Dore J. 2005 - 28.
Jernberg C. Lofmark S. Edlund C. Jansson J. K. Long-term impacts of antibiotic exposure on the human intestinal microbiota 2010 3216 EOF 3223 EOF - 29.
McFarland LV. Antibiotic-associated diarrhea: epidemiology, trends and treatment. Future Microbiol2008 - 30.
Metchnikoff E. The prolongation of life: optimistic studies. G.P. Putnam’s Sons ed. New York and London:1908 - 31.
FAO/WHO. Health and nutritional porperties of probiotics in food includion powder milk with live lactic acid bacteria. 30[suppl 2], S23 S33.2001 Argentina. - 32.
FAO/WHO Working group. Guidelines for the evaluation of probiotics in food.2002 . London, 30 avril-1er mai. - 33.
Williams NT. Probiotics. Am J Health Syst Pharm 2010,67:449-458. - 34.
Deshpande G. Rao S. Patole S. Progress in the field of probiotics: year 2011 Curr Opin Gastroenterol2011 13 EOF 18 EOF - 35.
Park J, Floch MH. Prebiotics, probiotics, and dietary fiber in gastrointestinal disease. Gastroenterol Clin North Am 2007,36:47-63. - 36.
Girardin M. Seidman E. G. Indications for the use of probiotics in gastrointestinal diseases Dig Dis2011 574 EOF 587 EOF - 37.
NutrRoberfroid M. Prebiotics the. concept revisited. J. 2007 S-837S. - 38.
Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: what are the risks? Am J Clin Nutr2006 - 39.
Braegger C. Chmielewska A. Decsi T. Kolacek S. Mihatsch W. Moreno L. Piescik M. Puntis J. Shamir R. Szajewska H. Turck D. van G. J. Supplementation of infant formula with probiotics and/or prebiotics: a systematic review and comment by the ESPGHAN committee on nutrition J Pediatr Gastroenterol Nutr2011 238 EOF 250 EOF - 40.
Agostoni C. Goulet O. Kolacek S. Koletzko B. Moreno L. Puntis J. Rigo J. Shamir R. Szajewska H. Turck D. Fermented infant formulae without live bacteria. J Pediatr Gastroenterol Nutr2007 392 EOF 7 EOF - 41.
Menard S. Candalh C. Ben A. M. Rakotobe S. Gaboriau-Routhiau V. Cerf-Bensussan N. Heyman M. Stimulation of immunity without alteration of oral tolerance in mice fed with heat-treated fermented infant formula J Pediatr Gastroenterol Nutr2006 451 EOF - 42.
Hoarau C. Lagaraine C. Martin L. Velge-Roussel F. Lebranchu Y. Supernatant of Bifidobacterium breve induces dendritic cell maturation, activation, and survival through a Toll-like receptor 2 pathway J Allergy Clin Immunol2006 696 EOF 702 EOF - 43.
Adlerberth I. Wold A. E. Establishment of the gut microbiota in Western infants Acta Paediatr2009 229 EOF 238 EOF - 44.
Establishment of the intestinal microflora in neonates]. Gastroenterol Clin BiolCampeotto F. Waligora-Dupriet A. J. Doucet-Populaire F. Kalach N. Dupont C. MJ Butel [. 2007 533 EOF 42 EOF - 45.
Isolation of bifidobacteria from breast milk and assessment of the bifidobacterial population by PCR-DGGE and qRTi-PCR. Appl Environ MicrobiolMartin R. Jimenez E. Heilig H. Fernandez L. Marin M. L. Zoetendal E. G. Rodriguez J. M. 2009 - 46.
Establishment and development of lactic acid bacteria and bifidobacteria microbiota in breast-milk and the infant gut. AnaerobeSolis G. de los-Gavilan Reyes. Fernandez C. G. Margolles N. Gueimonde A. M. 2010 - 47.
Palmer C. Bik E. M. Digiulio D. B. Relman D. A. Brown P. O. Development of the Human Infant Intestinal Microbiota PLoS Biol2007 e177. - 48.
Biasucci G. Benenati B. Morelli L. Bessi E. Boehm G. Cesarean delivery may affect the early biodiversity of intestinal bacteria. J Nutr2008 1796S EOF 1800S EOF - 49.
Huurre A, Kalliomaki M, Rautava S, Rinne M, Salminen S, Isolauri E. Mode of delivery- effects on gut microbiota and humoral immunity. Neonatology 2008,93:236-240. - 50.
Jacquot A. Neveu D. Aujoulat F. Mercier G. Marchandin H. Jumas-Bilak E. Picaud J. C. Dynamics and Clinical Evolution of Bacterial Gut Microflora in Extremely Premature Patients J Pediatr2010 390 EOF 396 EOF - 51.
Mshvildadze M. Neu J. Shuster J. Theriaque D. Li N. Mai V. Intestinal microbial ecology in premature infants assessed with non-culture-based techniques J Pediatr20 EOF 25 EOF - 52.
Chang J. Y. Shin S. M. Chun J. Lee J. H. Seo J. K. Pyrosequencing-based molecular monitoring of the intestinal bacterial colonization in preterm infants J Pediatr Gastroenterol Nutr2011 512 EOF 519 EOF - 53.
LaTuga MS, Ellis JC, Cotton CM, Goldberg RN, Wynn JL, Jackson RB, Seed PC. Beyond bacteria: a study of the enteric microbial consortium in extremely low birth weight infants. PLoS One2011 e27858. - 54.
MJ Butel Suau. A. Campeotto F. Magne F. Aires J. Ferraris L. Kalach N. Leroux B. Dupont C. Conditions of bifidobacterial colonization in preterm infants: a prospective analysis. J Pediatr Gastroenterol Nutr2007 577 EOF 82 EOF - 55.
Moore DC, Elsas PX, Maximiano ES, Elsas MI. Impact of diet on the immunological microenvironment of the pregnant uterus and its relationship to allergic disease in the offspring--a review of the recent literature. Sao Paulo Med J2006 298 EOF 303 EOF - 56.
Okada H. Kuhn C. Feillet H. Bach J. F. The’hygiene hypothesis’ for autoimmune and allergic diseases: an update. Clin Exp Immunol1 EOF 9 EOF - 57.
Protonotariou E. Malamitsi-Puchner A. Rizos D. Papagianni B. Moira E. Sarandakou A. Botsis D. Age-related differentiations of Th1/Th2 cytokines in newborn infants Mediators Inflamm2004 89 EOF 92 EOF - 58.
MM Grönlund Lehtonen. O. P. Eerola E. Kero P. Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J Pediat Gastroenterol Nutr19 EOF 25 EOF - 59.
MM Grönlund Arvilommi. H. Kero P. Lehtonen O. P. Isolauri E. Importance of intestinal colonisation in the maturation of humoral immunity in early infancy: a prospective follow up study of healthy infants aged Arch Dis Child Fetal Neonatal Ed0 6 months.2000 F186-F192. - 60.
Rautava S. Ruuskanen O. Ouwehand A. Salminen S. Isolauri E. The hygiene hypothesis of atopic disease--an extended version. J Pediatr Gastroenterol Nutr2004 378 EOF 88 EOF - 61.
Mode of delivery and asthma-- is there a connection? Pediatr ResKero J. Gissler M. MM Gronlund Kero. P. Koskinen P. Hemminki E. Isolauri E. 2002 - 62.
Laubereau B. Filipiak-Pittroff B. BA von Grubl. A. Reinhardt D. Wichmann H. E. Koletzko S. Caesarean section and gastrointestinal symptoms, atopic dermatitis, and sensitisation during the first year of life Arch Dis Child2004 - 63.
Agosti M. Vegni C. Gangi S. Benedetti V. Marini A. Allergic manifestations in very low-birthweight infants: a Acta Paediatr Suppl6 -year follow-up.2003 - 64.
Mc Keever T. M. Lewis S. A. Smith C. Collins J. Heatlie H. Frischer M. Hubbard R. Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database J Allergy Clin Immunol2002 - 65.
Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clin Exp AllergySjogren Y. M. Jenmalm M. C. Bottcher M. F. Bjorksten B. Sverremark-Ekstrom E. 2009 518 EOF 526 EOF - 66.
Bjorksten B. Sepp E. Julge K. Voor T. Mikelsaar M. Allergy development and the intestinal microflora during the first year of life J Allergy Clin Immunol2001 - 67.
Sepp E. Julge K. Mikelsaar M. Bjorksten B. Intestinal microbiota and immunoglobulin E responses in Clin Exp Allergy5 -year-old Estonian children2005 - 68.
Hong P. Y. Lee B. W. Aw M. Shek L. P. Yap G. C. Chua K. Y. Liu W. T. Comparative analysis of fecal microbiota in infants with and without eczema PLoS One2010 e9964. - 69.
Kalliomaki M. Collado M. C. Salminen S. Isolauri E. Early differences in fecal microbiota composition in children may predict overweight Am J Clin Nutr2008 534 EOF 538 EOF - 70.
De Cruz P. Prideaux L. Wagner J. Ng S. C. Mc Sweeney C. Kirkwood C. Morrison M. MA Kamm Characterization of the gastrointestinal microbiota in health and inflammatory bowel disease. Inflamm Bowel Dis2012 372 EOF 90 EOF - 71.
Intestinal microbiota in inflammatory bowel disease: friend of foe? World J GastroenterolFava F. Danese S. 2011 - 72.
Conte M. P. Schippa S. Zamboni I. Penta M. Chiarini F. Seganti L. Osborn J. Falconieri P. Borrelli O. Cucchiara S. Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease. 2006 1760 EOF 7 EOF - 73.
Schippa S, Iebba V, Barbato M, Di NG, Totino V, Checchi MP, Longhi C, Maiella G, Cucchiara S, Conte MP. A distinctive’microbial signature’ in celiac pediatric patients. BMC Microbiol 2010,10:175. - 74.
Schippa S. Conte M. P. Borrelli O. Iebba V. Aleandri M. Seganti L. Longhi C. Chiarini F. Osborn J. Cucchiara S. Dominant genotypes in mucosa-associated Escherichia coli strains from pediatric patients with inflammatory bowel disease Inflamm Bowel Dis2009 661 EOF 672 EOF - 75.
Collado M. C. Donat E. Ribes-Koninckx C. Calabuig M. Sanz Y. Specific duodenal and faecal bacterial groups associated with paediatric coeliac disease J Clin Pathol2009 - 76.
Bolte ER. The role of cellular secretion in autism spectrum disorders: a unifying hypothesis Med Hypotheses2003 119 EOF 122 EOF - 77.
Finegold S. M. Molitoris D. Song Y. Liu C. Vaisanen M. L. Bolte E. Mc Teague M. Sandler R. Wexler H. Marlowe E. M. MD Collins Lawson. P. A. Summanen P. Baysallar M. Tomzynski T. J. Read E. Johnson E. Rolfe R. Nasir P. Shah H. Haake D. A. Manning P. Kaul A. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis2002 S6 S16. - 78.
Song Y, Liu C, Finegold SM. Real-time PCR quantitation of clostridia in feces of autistic children. Appl Environ Microbiol 2004,70:6459-6465. - 79.
Finegold S. M. Downes J. Summanen P. H. Microbiology of regressive autism. 2012 260 EOF 2 EOF - 80.
Thavagnanam S, Fleming J, Bromley A, Shields MD, Cardwell CR. A meta-analysis of the association between Caesarean section and childhood asthma. Clin Exp Allergy 2008,38:629-633. - 81.
Bager P. Birth by caesarean section and wheezing, asthma, allergy, and intestinal disease. Clin Exp Allergy2011 147 EOF 8 EOF - 82.
Bager P. Melbye M. Rostgaard K. Benn C. S. Westergaard T. Mode of delivery and risk of allergic rhinitis and asthma. J Allergy Clin Immunol2003 51 EOF 6 EOF - 83.
Decker E. Hornef M. Stockinger S. Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children Gut Microbes2011 - 84.
Ajslev T. A. Andersen C. S. Gamborg M. Sorensen T. I. Jess T. Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics. Int J Obes (Lond)2011 522 EOF 9 EOF - 85.
Zhou L. He G. Zhang J. Xie R. Walker M. Wen S. W. Risk factors of obesity in preschool children in an urban area in China Eur J Pediatr2011 1401 EOF 1406 EOF - 86.
Huh S. Y. Rifas-Shiman S. L. CA Zera Edwards. J. W. Oken E. Weiss S. T. Gillman M. W. Delivery by caesarean section and risk of obesity in preschool age children: a prospective cohort study Arch Dis Child2012 Epub ahead of print]. - 87.
Cardwell C. R. Stene L. C. Joner G. Cinek O. Svensson J. MJ Goldacre Parslow. R. C. Pozzilli P. Brigis G. Stoyanov D. Urbonaite B. Sipetic S. Schober E. Ionescu-Tirgoviste C. Devoti G. CE de Beaufort Buschard. K. Patterson C. C. Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies 2008 726 EOF 735 EOF - 88.
Davis JN, Whaley SE, Goran MI. Effects of breastfeeding and low sugar-sweetened beverage intake on obesity prevalence in Hispanic toddlers Am J Clin Nutr2012 3 EOF 8 EOF - 89.
Thomas DW, Greer FR. Probiotics and prebiotics in pediatrics 2010 1217 EOF 1231 EOF - 90.
Hsieh M. H. Versalovic J. The human microbiome and probiotics: implications for pediatrics Curr Probl Pediatr Adolesc Health Care2008 309 EOF 327 EOF - 91.
Allen SJ, Martinez EG, Gregorio GV, Dans LF. Probiotics for treating acute infectious diarrhoea. Cochrane Database Syst Rev2010 CD003048 EOF - 92.
Szajewska H. Ruszczynski M. Radzikowski A. Probiotics in the prevention of antibiotic-associated diarrhea in children: A meta-analysis of randomized controlled trials J Pediatr2006 367 EOF 372 EOF - 93.
Johnston B. C. Goldenberg J. Z. Vandvik P. O. Sun X. Guyatt G. H. Probiotics for the prevention of pediatric antibiotic-associated diarrhea. Cochrane Database Syst Rev2011 CD004827 EOF - 94.
Cohen-Silver J. Ratnapalan S. Management of infantile colic: a review Clin Pediatr (Phila)2009 14 EOF 17 EOF - 95.
Savino F. Pelle E. Palumeri E. Oggero R. Miniero R. Lactobacillus reuteri (American Type Culture Collection Strain 55730) versus simethicone in the treatment of infantile colic: a prospective randomized study. 2007 e124 e130. - 96.
Savino F. Cordisco L. Tarasco V. Locatelli E. Di Oggero G. D. Matteuzzi R. D. Antagonistic effect of Lactobacillus strains against gas-producing coliforms isolated from colicky infants. BMC Microbiol2011 157 EOF - 97.
Mohan R. Koebnick C. Schildt J. Mueller M. Radke M. Blaut M. Effects of Bifidobacterium lactis supplementation on body weight, fecal pH, acetate, lactate, calprotectin and IgA in preterm infants. Pedi atr Res2008 418 EOF 422 EOF - 98.
An alpha-lactalbumin-enriched and symbiotic-supplemented v. a standard infant formula: a multicentre, double-blind, randomised trial. Br J NutrRoze J. C. Barbarot S. MJ Butel Kapel. N. Waligora-Dupriet A. J. De Leblanc M. I. Godon M. Soulaines N. Darmaun P. Rivero D. Dupont M. C. 2012 - 99.
Rinne M. Kalliomaki M. Arvilommi H. Salminen S. Isolauri E. Effect of probiotics and breastfeeding on the Bifidobacterium and Lactobacillus/Enterococcus microbiota and humoral immune responses. J Pediatr2005 186 EOF 91 EOF - 100.
Sherman MP. New concepts of microbial translocation in the neonatal intestine: mechanisms and prevention Clin Perinatol2010 565 EOF 579 EOF - 101.
Betsi G. I. Papadavid E. ME Falagas Probiotics for the treatment or prevention of atopic dermatitis: a review of the evidence from randomized controlled trials Am J Clin Dermatol2008 93 EOF 103 EOF - 102.
Waligora-Dupriet AJ, Butel MJ. Microbiota and allergy: from dysbiosis to probiotics. In: Pereira C, editor. Allergic Diseases- Highlights in the Clinic, Mechanisms and Treatment. Rijeka: Intech;2012 413 434 - 103.
Kalliomaki M. Kirjavainen P. Eerola E. Kero P. Salminen S. Isolauri E. Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing J Allergy Clin Immunol2001 - 104.
Kalliomaki M. Salminen S. Poussa T. Arvilommi H. Isolauri E. Probiotics and prevention of atopic disease: 4 -year follow-up of a randomised placebo-controlled trial.2003 - 105.
Kalliomaki M. Salminen S. Poussa T. Isolauri E. Probiotics during the first 7 years of life: a cumulative risk reduction of eczema in a randomized, placebo-controlled trial J Allergy Clin Immunol2007 1019 EOF 1021 EOF - 106.
Kopp MV, Hennemuth I, Heinzmann A, Urbanek R. Randomized, double-blind, placebo-controlled trial of probiotics for primary prevention: no clinical effects of Lactobacillus GG supplementation. Pediatrics 2008,121:e850-e856. - 107.
Abrahamsson T. R. Jakobsson T. Bottcher M. F. Fredrikson M. Jenmalm M. C. Bjorksten B. Oldaeus G. Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial J Allergy Clin Immunol2007 1174 EOF 1180 EOF - 108.
Wickens K, Black PN, Stanley TV, Mitchell E, Fitzharris P, Tannock GW, Purdie G, Crane J. A differential effect of 2 probiotics in the prevention of eczema and atopy: a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 2008,122:788-794. - 109.
Taylor AL, Dunstan JA, Prescott SL. Probiotic supplementation for the first 6 months of life fails to reduce the risk of atopic dermatitis and increases the risk of allergen sensitization in high-risk children: a randomized controlled trial J Allergy Clin Immunol2007 184 EOF 191 EOF - 110.
Taylor A. Hale J. Wiltschut J. Lehmann H. Dunstan J. A. Prescott S. L. Evaluation of the effects of probiotic supplementation from the neonatal period on innate immune development in infancy Clin Exp Allergy2006 1218 EOF 1226 EOF - 111.
Soh S. E. Aw M. Gerez I. Chong Y. S. Rauff M. Ng Y. P. Wong H. B. Pai N. Lee B. W. Shek L. P. Probiotic supplementation in the first 6 months of life in at risk Asian infants--effects on eczema and atopic sensitization at the age of 1 year. Clin Exp Allergy2009 571 EOF 578 EOF - 112.
Szajewska H. Early nutritional strategies for preventing allergic disease. Isr Med Assoc J2012 58 EOF 62 EOF - 113.
Boyle R. J. Bath-Hextall F. J. Leonardi-Bee J. Murrell D. F. Tang M. L. Probiotics for treating eczema. Cochrane Database Syst Rev2008 CD006135 EOF - 114.
Menard O. MJ Butel-Routhiau Gaboriau. Waligora-Dupriet V. A. J. Gnotobiotic mouse immune response induced by Bifidobacterium sp. strains isolated from infants Appl Environ Microbiol2008 660 EOF 666 EOF - 115.
De Bandt JP, Waligora-Dupriet AJ, Butel MJ. Intestinal microbiota in inflammation and insulin resistance: relevance to humans Curr Opin Clin Nutr Metab Care2011 334 EOF 340 EOF - 116.
The impact of childhood obesity on morbidity and mortality in adulthood: a systematic review. Obes RevPark M. H. Falconer C. Viner R. M. Kinra S. 2012 Epub ahead of print]. - 117.
Nadal I, Santacruz A, Marcos A, Warnberg J, Garagorri M, Moreno LA, Martin-Matillas M, Campoy C, Marti A, Moleres A, Delgado M, Veiga OL, Garcia-Fuentes M, Redondo CG, Sanz Y. Shifts in Clostridia, Bacteroides and immunoglobulin-coating fecal bacteria associated with weight loss in obese adolescents. Int J Obes (Lond) 2009,33:758-767. - 118.
Balamurugan R. George G. Kabeerdoss J. Hepsiba J. Chandragunasekaran A. M. BS Ramakrishna Quantitative differences in intestinal Faecalibacterium prausnitzii in obese Indian children Br J Nutr2010 335 EOF 338 EOF - 119.
Luoto R. Kalliomaki M. Laitinen K. Isolauri E. The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years. Int J Obes (Lond)2010 1531 EOF 7 EOF - 120.
Probiotics to obese adolescents; RCT examining the effects on inflammation and metabolic syndrome. J Pediatr Gastroenterol NutrGobel R. J. Larsen N. Jakobsen M. Molgaard C. Michaelsen K. F. 2012 Epub ahead of print]. - 121.
Blakey J. L. Lubitz L. Barnes G. L. Bishop R. F. Campbell N. T. Gillam G. L. Development of gut colonisation in pre-term neonates. J Med Microbiol1982 519 EOF 29 EOF - 122.
Sakata H. Yoshioka H. Fujita K. Development of the intestinal flora in very low birth weight infants compared to normal full-term newborns. Eur J Pediatr1985 186 EOF 90 EOF - 123.
Stark P. L. Lee A. The bacterial colonization of the large bowel of pre-term low birth weight neonates J Hyg Camb1982 59 EOF - 124.
Campeotto F, Suau A, Kapel N, Magne F, Viallon V, Ferraris L, Waligora-Dupriet AJ, Soulaines P, Leroux B, Kalach N, Dupont C, Butel MJ. A fermented formula in preterm infants: clinical tolerance, gut microbiota, down regulation of fecal calprotectin, and up regulation of fecal secretory IgA. Br J Nutr 2011,105:1843-1851. - 125.
Gewolb I. H. Schwalbe R. S. Taciak V. L. Harrison T. S. Panigrahi P. Stool microflora in extremely low birthweight infants Arch Dis Child Fetal Neonatal Ed1999 F167 F173. - 126.
Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Am J Clin NutrRouge C. Piloquet H. MJ Butel Berger. B. Rochat F. Ferraris L. Des R. C. Legrand A. De La Cochetiere M. F. N’Guyen J. M. Vodovar M. Voyer M. Darmaun D. Roze J. C. 2009 - 127.
Millar MR, Linton CJ, Cade A, Glancy D, Hall M, Jalal H. Application of 16S rRNA gene PCR to study bowel flora of preterm infants with and without necrotizing enterocolitis. J Clin Microbiol 1996,34:2506-2510. - 128.
Roudiere L. Jacquot A. Marchandin H. Aujoulat F. Devine R. Zorgniotti I. Jean-Pierre H. Picaud J. C. Jumas-Bilak E. Optimized PCR-Temporal Temperature Gel Electrophoresis compared to cultivation to assess diversity of gut microbiota in neonates J Microbiol Methods2009 156 EOF 165 EOF - 129.
Schwiertz A. Gruhl B. Lobnitz M. Michel P. Radke M. Blaut M. Development of the intestinal bacterial composition in hospitalized preterm infants in comparison with breast-fed, full-term infants. Pediatr Res2003 393 EOF 9 EOF - 130.
Wang Y, Hoenig JD, Malin KJ, Qamar S, Petrof EO, Sun J, Antonopoulos DA, Chang EB, Claud EC. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. ISME J 2009,3:944-954. - 131.
Ferraris L. MJ Butel Campeotto. F. Vodovar M. Roze J. C. Aires J. Clostridia in premature neonates’ gut: incidence, antibiotic susceptibility, and perinatal determinants influencing colonization PLoS One2012 e30594. - 132.
Stoll B. J. Hansen N. I. Higgins R. D. AA Fanaroff Duara. S. Goldberg R. Laptook A. Walsh M. Oh W. Hale E. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, Pediatr Infect Dis J2002 2003 .2005 - 133.
Smith A. Saiman L. Zhou J. Della -Latta P. Jia H. Graham P. L. I. I. I. Concordance of gastrointestinal tract colonization and subsequent bloodstream infections with gram-negative bacilli in very low birth weight infants in the neonatal intensive care unit Pediatr Infect Dis J2010 831 EOF 835 EOF - 134.
Das P. Singh A. K. Pal T. Dasgupta S. Ramamurthy T. Basu S. Colonization of the gut with Gram-negative bacilli, its association with neonatal sepsis and its clinical relevance in a developing country J Med Microbiol2011 1651 EOF 1660 EOF - 135.
Obladen M. Necrotizing enterocolitis--1. years of. fruitless search. for the. cause 2009 203 EOF 210 EOF - 136.
MJ Morowitz Poroyko. V. Caplan M. Alverdy J. Liu D. C. Redefining the role of intestinal microbes in the pathogenesis of necrotizing enterocolitis 2010 777 EOF 785 EOF - 137.
Waligora-Dupriet A. J. Dugay A. Auzeil N. Huerre M. MJ Butel Evidence for clostridial implication in necrotizing enterocolitis through bacterial fermentation in a gnotobiotic quail model. Pediatr Res2005 629 EOF 35 EOF - 138.
Lin PW, Nasr TR, Stoll BJ. Necrotizing enterocolitis: recent scientific advances in pathophysiology and prevention. Semin Perinatol2008 70 EOF 82 EOF - 139.
Waligora-Dupriet A. J. Dugay A. Auzeil N. Nicolis I. Rabot S. Huerre M. R. MJ Butel Short-chain fatty acids and polyamines in the pathogenesis of necrotizing enterocolitis: Kinetics aspects in gnotobiotic quails 2009 138 EOF 144 EOF - 140.
Kien CL. Colonic fermentation of carbohydrate in the premature infant : possible relevance to necrotizing enterocolitis J Pediatr1990 S52 S58. - 141.
Lin J. Too much short chain fatty acids cause neonatal necrotizing enterocolitis. Med Hypotheses2004 291 EOF 3 EOF - 142.
Szylit O. Maurage C. Gasqui P. Popot F. Favre A. Gold F. Borderon J. C. Fecal short-chain fatty acids predict digestive disorders in premature infants. J Parent Enter Nutr1998 136 EOF 41 EOF - 143.
Clostridial pathogenicity in experimental necrotising enterocolitis in gnotobiotic quails and protective role of bifidobacteria. J Med MicrobiolMJ Butel Roland. N. Hibert A. Popot F. Favre A. Tessèdre A. C. Bensaada M. Rimbault A. Szylit O. 1998 - 144.
Early intestinal bacterial colonization and necrotizing enterocolitis in premature infants: the putative role of Clostridium. Pediatr ResDe La Cochetière M. F. Piloquet H. Des Robert. C. Darmaun D. Galmiche J. P. Rozé J. C. 2004 - 145.
Mai V. Young C. M. Ukhanova M. Wang X. Sun Y. Casella G. Theriaque D. Li N. Sharma R. Hudak M. Neu J. Fecal microbiota in premature infants prior to necrotizing enterocolitis PLoS One2011 e20647. - 146.
Alfaleh K. Anabrees J. Bassler D. Al-Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev2011 CD005496 EOF - 147.
Alfaleh K. Anabrees J. Bassler D. Probiotics reduce the risk of necrotizing enterocolitis in preterm infants: a meta-analysis 2010 93 EOF 99 EOF - 148.
Deshpande G. Rao S. Patole S. Bulsara M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates 2010 921 EOF 930 EOF - 149.
Luoto R. Matomaki J. Isolauri E. Lehtonen L. Incidence of necrotizing enterocolitis in very-low-birth-weight infants related to the use of Lactobacillus GG Acta Paediatr2010 1135 EOF 1138 EOF - 150.
Tarnow-Mordi W. O. Wilkinson D. Trivedi A. Brok J. Probiotics reduce all-cause mortality and necrotizing enterocolitis: it is time to change practice 2010 1068 EOF 1071 EOF - 151.
Nonadministration of routine probiotics unethical--really? PediatricsNeu J. Shuster J. 2010 e740 e741. - 152.
Soll RF. Probiotics: are we ready for routine use? Pediatrics 2010,125:1071-1072. - 153.
Chou IC, Kuo HT, Chang JS, Wu SF, Chiu HY, Su BH, Lin HC. Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight infants J Pediatr2010 393 EOF 396 EOF - 154.
Ohishi A. Takahashi S. Ito Y. Ohishi Y. Tsukamoto K. Nanba Y. Ito N. Kakiuchi S. Saitoh A. Morotomi M. Nakamura T. Bifidobacterium septicemia associated with postoperative probiotic therapy in a neonate with omphalocele J Pediatr2010 679 EOF 681 EOF - 155.
MS Cilieborg Thymann. T. Siggers R. Boye M. Bering S. B. Jensen B. B. Sangild P. T. The incidence of necrotizing enterocolitis is increased following probiotic administration to preterm pigs J Nutr2011 223 EOF 230 EOF - 156.
Honeycutt T. C. El Wardrop K. M. Mc Neal-Trice R. M. I. I. I. Honeycutt K. Christy A. L. Mistry C. G. Harris K. BD Meliones J. N. Kocis K. C. Probiotic administration and the incidence of nosocomial infection in pediatric intensive care: a randomized placebo-controlled trial. Pediatr Crit Care Med2007 452 EOF 8%3B EOF - 157.
Manzoni P. Lista G. Gallo E. Marangione P. Priolo C. Fontana P. Guardione R. Farina D. Routine Lactobacillus rhamnosus GG administration in VLBW infants: a retrospective, Early Hum Dev6 -year cohort study2011 Suppl 1:S35-S38. - 158.
Routine probiotics for premature infants: let’s be careful! J PediatrNeu J. 2011 - 159.
Deshpande GC, Rao SC, Keil AD, Patole SK. Evidence-based guidelines for use of probiotics in preterm neonates. BMC Med2011 92 EOF - 160.
Mihatsch W. A. CP Braegger Decsi. T. Kolacek S. Lanzinger H. Mayer B. Moreno L. A. Pohlandt F. Puntis J. Shamir R. Stadtmuller U. Szajewska H. Turck D. van Goudoever J. B. Critical systematic review of the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants Clin Nutr2012 6 EOF 15 EOF - 161.
Mihatsch WA. What is the power of evidence recommending routine probiotics for necrotizing enterocolitis prevention in preterm infants? Curr Opin Clin Nutr Metab Care2011 - 162.
BMC Infect DisGarland S. M. Tobin J. M. Pirotta M. Tabrizi S. N. Opie G. Donath S. Tang M. L. Morley C. J. Hickey L. Ung L. Jacobs S. E. The Pro. Prems trial. investigating the. effects of. probiotics on. late onset. sepsis in. very preterm. infants B. M. 2011 - 163.
Probiotics and prebiotics in preterm infants: Where are we? Where are we going? Early Hum DevSzajewska H. 2010 Suppl1 81 86 - 164.
Agostoni C. Buonocore G. Carnielli V. P. De Darmaun C. M. Decsi D. Domellof T. Embleton M. Fusch N. D. Genzel-Boroviczeny C. Goulet O. Kalhan O. Kolacek S. C. Koletzko S. Lapillonne B. Mihatsch A. Moreno W. Neu L. Poindexter J. Puntis B. Putet J. Rigo G. Riskin J. Salle A. Sauer B. Shamir P. Szajewska R. Thureen H. Turck P. van Goudoever D. Ziegler J. B. EE Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition J Pediatr Gastroenterol Nutr2010 85 EOF 91 EOF