Abstract
Purpose of Review
Probiotics intake may be considered beneficial by prospective and pregnant mothers, but their effects on offspring development are incompletely understood. The purpose of this review was to examine recent pre-clinical and clinical studies to understand how maternal probiotics exposure affects offspring health outcomes.
Recent Findings
Effects were investigated in the context of supporting offspring growth, intestinal health, and gut microbiota, preventing allergic diseases, supporting neurodevelopment, and preventing metabolic disorders in pre-clinical and clinical studies. Most human studies focused on infancy outcomes, whereas pre-clinical studies also examined outcomes at adolescence and young adulthood. While still understudied, both pre-clinical and clinical studies propose epigenetic modifications as an underlying mechanism. Optimal timing of intervention remains unclear.
Summary
Administration of selected probiotics to mothers has programming potential for sustaining life-long health of offspring. Administration protocols, specific windows of susceptibility, and individual-specific responses need to be further studied.
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Introduction
Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” [1]. Probiotics can be delivered in various modalities such as dietary supplements, food products, or drugs, targeting individuals across the entire life spectrum. Probiotics stem from various taxa including both prokaryotic and eukaryotic microorganisms and display common and/or strain-specific benefits such as regulation of intestinal transit, competitive exclusion of pathogens, vitamin and specific bioactive synthesis, intestinal barrier enhancement, or immunomodulation [1]. The gut ecosystem is a determinant of health and a main target of probiotics administration. Established in early life, altered dynamics in this process are associated with disease later in life, such as asthma [2], allergy [3], eczema [3], obesity [4, 5], and susceptibility to infection [6]. Several probiotics have been studied for their role in early stages of life and ability to sustain health in mothers and children. Substantiated benefits in the context of eczema for lactobacilli alone or in combination with Bifidobacterium species administered to mothers or infants [7] have been translated into guidelines by the World Allergy Organization in 2015 [8]. These guidelines indicate that probiotic consumption during pregnancy might be beneficial for pregnant or breastfeeding women at high risk for having a child who develops allergies. Additional benefits of maternally administered probiotics include improvement of metabolic parameters (insulin levels and insulin resistance, very low density lipoprotein and total cholesterol concentration) in gestational diabetes mellitus (GDM) [9], reduced rectal and vaginal Group B Streptococci colonization before parturition (important to prevent offspring mortality caused by Early Onset Group B Streptococcus disease) [10], and reduced incidence of mastitis [11]. These studies are sparse and heterogeneous in terms of probiotics usage, vehicle, and dosage. Because maternal exposures such as metabolic syndrome and infection are associated with offspring outcomes [12, 13], it is likely that offspring can also be affected by maternal use of probiotics. In fact, maternal probiotics administration was shown to result in temporary colonization of the offspring and/or modulation of the offspring microbiota [14, 15].
In a recent meta-analysis, probiotic consumption during pregnancy and/or lactation was shown to be generally safe for pregnant mothers in terms of gastrointestinal symptoms, tachycardia, vaginal discharge, eczema, and headache [16]. Only one probiotic mix containing Lacticaseibacillus rhamnosus GR-1 and Limosilactobacillus reuteri RC-14 was associated with an increased risk of vaginal discharge and changes in stool consistency after consumption during the first and second trimesters of pregnancy [17]. Direct probiotic administration to infants between birth and 2 years of age has also been reported as safe. This was shown through a systematic review that stratified the incidence of an adverse effect according to the infant’s health condition (healthy, low-birth weight, dermatitis, diarrhea, or formula-fed) [18]. The utilization of probiotics during these sensitive periods of life could therefore be considered to support infant health. A survey conducted in Canada suggests that the public already utilizes probiotics as 50.8% of women with a child aged 2 years or younger reported giving a probiotic product to their infant. Responses came from 413 mothers enrolled in the Alberta Pregnancy Outcomes and Nutrition (APrON) study in 2012 [19].
It is known that an altered maternal microbiota during pregnancy can affect offspring microbiota establishment, immune development, and metabolic health throughout life [20,21,22]. Thus, interventions targeting the maternal microbiota, such as probiotics, may have the potential to program offspring health. The purpose of this review was to examine recent literature from pre-clinical and clinical studies on the effects of probiotic administration started during the pre-conception period or pregnancy on offspring outcomes.
Search Strategy and Selection Criteria
PubMed, Embase, and Cochrane Library were searched for original research articles including pre-clinical (animal) and clinical studies and meta-analyses over the last 5 years (January 2017–March 2022). The search terms used were as follows: “probiotics”, “gestation”, “pregnancy”, “lactation”, “pre-conception” or “preconception”, “pre-mating” or “premating”, “pre-conceptional”, combined or not with “offspring”, “infant”, “baby” and complemented with manual inspection of reference lists of the selected articles. Articles were selected if they included a probiotic intervention starting at pre-conception and/or during pregnancy and assessed offspring outcomes. Studies of probiotics administered in combination with other ingredients were included. We included studies using substantiated probiotics strains, according to the Food and Agriculture Organization of the United Nations (FAO) guidelines [23], as well as strains for which research is ongoing, especially at the clinical stage.
Articles were screened to retrieve information about the probiotic strains, dose, vehicle, and supplementation period and this information is reported in tabulated form according to the Population, Interventions, Comparisons, Outcomes and Study designs (PICOS) elements [24] and grouped as pre-clinical (Table 1) or clinical (Table 2) studies. Findings are discussed according to 6 offspring outcomes identified across the studies: (1) growth and anthropometric indices at birth (19 articles); (2) intestinal barrier and gut health (14 articles); (3) neurodevelopment and anxiety-like behavior (8 articles); (4) allergic diseases (12 articles); (5) metabolic disorders (14 articles); and (6) intestinal microbiota (18 articles).
Probiotics in the Context of the Developmental Origins of Health and Disease
The Developmental Origins of Health and Disease (DOHaD) paradigm is based on the principle of developmental plasticity, which refers to the phenomenon by which “a given genotype can give rise to a range of different physiological or morphological states in response to various environmental exposures throughout development.” The term programming refers to a stimulus introduced at a “critical” or “sensitive” period, which causes long-term consequences for an organism [25]. A key principle of DOHaD is the existence of “windows of opportunity”, i.e., the prenatal stages of life (from pre-conception to embryonic and fetal stages and birth), infancy, and adolescence [25]. These time-sensitive life stages of exposure lead to tissue-specific effects thought to optimize or alter one’s biological potentials, and promote long-term health or a disease state [26, 27]. For example, undernutrition during pregnancy induces structure and functional remodeling in the fetus preserving brain development and prioritizing survival, negatively impacting development of other functions such as glucose metabolism and insulin sensitivity [26]. With time, as the evolutionary advantage of developmental plasticity begins to decrease, an individual’s ability to adapt to positive or negative environmental challenges becomes more limited [26]. Historically, the area of DOHaD research has primarily focused on overnutrition or undernutrition, linked with the manifestation of non-communicable diseases in later life, such as obesity or diabetes mellitus. Prenatal and early infancy exposures have been specifically studied at the macro- and micro-nutrient levels, with offspring outcomes ranging from glucose homeostasis to blood pressure [28]. In utero epigenetic modifications may be underlying mechanisms [29]. The gut microbiota has been proposed to regulate host gene expression epigenetically [30, 31], for example, via DNA methylation [32] with implications for offspring disease susceptibility [33]. The intestinal microbiota is a dynamic and interactive across-kingdom ecosystem composed of characteristic microbial communities co-evolving with their host [34]. While what constitutes a health-compatible microbiota remains elusive [35], many taxa have been identified whose altered representation is associated with diseases. Specifically, in infancy, microbiota variation is a predictor of overweight [5], asthma, and allergy [3]. The microbiota is seeded by the maternal microbiota [36] and continues to develop during infancy [37] thus going through sequential stages of plasticity that encompass pregnancy and are susceptible to programming, while being a determinant of life-long health [38]. In this context, maternally administered probiotics can be used as a dietary intervention that targets the offspring intestinal ecosystem. In utero and early life exposure to probiotics may affect growth and gut health [39,40,41], suggesting that specific windows of opportunities may exist for probiotic administration.
Growth and Anthropometric Indices at Birth
Probiotics have a long history of use to support growth of farm animals [42, 43]. Investigation into the underlying mechanisms suggests that they play a role in hormone metabolism. For example, certain Lactiplantibacillus plantarum strains support Drosophila melanogaster larval growth via target of rapamycin (TOR)-dependent mechanisms and hormonal growth signaling [44]. Lactiplantibacillus plantarum strains also support systemic growth in undernourished mice via growth hormone sensitivity enhancement and increased tissue insulin-like growth factor 1 activity [45]. Previous studies investigating the impact of maternal probiotics intake on offspring growth have largely focused on metabolic or allergic diseases as main outcomes [39, 46]. In recent studies in overweight women and women diagnosed with GDM, mid- or late-pregnancy supplementation with several mixtures of Lactobacillus, Bifidobacterium, and Streptococcus species had no effect on infant anthropometrics at birth [47,48,49,50,51]. Recently, several studies were also completed in healthy participants. As shown in Table 2, supplementation with various probiotic mixes starting at the beginning of pregnancy, at the second trimester, or at the end of pregnancy had no impact on neonatal birth weight, body mass index, birth length, femur length, or head circumference [52, 53, 54•, 55, 56•]. These findings align with a recent meta-analysis investigating infant birth weight following exposure to Lacticaseibacillus rhamnosus strains alone or in mixtures with Streptococcus or Bifidobacterium strains started during mid- or late-pregnancy [57]. Sex-specific effects have not been comprehensively studied.
Birth anthropometrics are important prognostic markers of healthy growth. Long-term effects of maternal probiotics on offspring growth during infancy and until adulthood have not been investigated in clinical studies; however, some studies have been conducted in animals. In healthy rodent models, the probiotic strains Limosilactobacillus fermentum CECT5716 and Lacticaseibacillus rhamnosus GG supplemented during pregnancy and lactation did not impact offspring body weight at weaning [58, 59]. Though supplementation with Bacillus subtilis PB6 or A and B from late pregnancy until weaning led to increased body weight in healthy piglet models (male and female combined) [60, 61]. Similarly, maternal intake of Lacticaseibacillus rhamnosus GG from late pregnancy until birth, combined with neonatal administration during the first five days of life, increased offspring weight during the four weeks after birth compared to the control mice that received the inactivated strain [62]. Findings were combined from male and female piglets. Interestingly, supplementation with Lactobacillus helveticus NS8 at the end of gestation in a healthy rat model led to a decreased body weight from late adolescence (51 days of life) until adulthood (76 and 86 days of life), without influencing the weight difference between males and females [63]. These findings suggest that the duration of the follow-up measurements is an important consideration to fully determine the effect of maternal probiotics exposure on offspring growth.
Intestinal Barrier and Gut Health
The intestinal barrier is critical to host health and a recognized target for preventative and therapeutic strategies [64]. The gut microbiota contributes to the protection of the epithelium from luminal pathogens and antigens, both physically and chemically [65], and supports the development of the infant immune system [3]. The intestinal barrier and the microbiota co-evolve in early life and reciprocally influence each other, resulting in the establishment of a mature intestinal ecosystem [66]. Probiotics have long been recognized to sustain the intestinal barrier, including in early life [40, 41]. Additionally, studies have proposed that the intestinal barrier, including the tight junction and the toll-like receptor associated pathways, is under epigenetic regulation [33]. Interestingly, in piglets, a recognized relevant model for pediatric nutritional studies assessing intestinal outcomes [67], maternal probiotics supplementation with Bacillus altitudinis WIT588 starting during late pregnancy increases intestinal crypt depth and villus length at postnatal day 34 [68]. In mice, supplementation with Lacticaseibacillus rhamnosus GG increases cell proliferation and differentiation and tight junction protein expression at postnatal day 21 [59, 62]. These findings suggest that maternal probiotic supplementation supports offspring intestinal digestive and absorptive functions in infancy [69]. Sex effects were not examined in these studies.
The long-term impact of this Lacticaseibacillus rhamnosus GG supplementation was investigated at 8 months of age when mice displayed increased goblet cell numbers and tight junction gene expression [59]. This was accompanied by increased antioxidant enzyme activities [59], and this increase was also demonstrated in the adult progeny of mini-sows that had received a Lactiplantibacillus plantarum B90 and Saccharomyces cerevisiae P11 mix, alone or with xylooligosaccharides, since the beginning of gestation [69]. This enhanced antioxidant capacity may help reduce ageing-associated oxidative stress and was associated with an increased jejunal villus height at 65 days [70]. Overall, findings from these pre-clinical studies suggest that maternal probiotic supplementation may help maintain gut barrier integrity in early life and adulthood and may improve antioxidant status. Indeed, recent studies support preventative effects of maternally administered probiotics in offspring with impaired intestinal barrier. In sows, maternal intake of Enterococcus faecium DSM7134 and Lactiplantibacillus plantarum CAM6 was shown to reduce diarrhea incidence in offspring [71, 72]. In a clinical trial, Limosilactobacillus reuteri LR92 supplementation to healthy mothers starting at late pregnancy and until birth led to a decreased colic frequency and severity in infants until 5 months of age, although the influence of sex on this effect was not reported [54•]. Interestingly, a recent study in mice showed that maternal administration of a mix of three Limosilactobacillus reuteri strains protected female offspring from dextran sodium sulfate-induced colitis [73••], although no protective effects were seen in male offspring. Taken together, these findings suggest that administration of selected probiotics during pregnancy may beneficially prevent intestinal inflammation in the offspring. More studies are required to understand sex-differences in responses and underlying mechanisms.
Neurodevelopment and Anxiety-Like Behavior
The gut ecosystem, including the microbiota, and the peripheral and central nervous system entertain a continuous bi-directional communication that is typically referred to as the gut-brain axis. Underlying mechanisms include endocrine pathways through cortisol and the hypothalamic–pituitary–adrenal axis, immunomodulation through cytokines, and interaction with the vagus nerve and the enteric nervous system [74]. The effects of probiotics on the gut-brain axis have been recently reviewed; Mörkl et al. demonstrated that probiotics may be therapeutically beneficial in the context of depression, but not schizophrenia, while data for anxiety are lacking [74]. Interestingly, these conditions may be rooted into neurodevelopment in early life and environmental exposures during stages of plasticity [75]. Moreover, the gut microbiota has been shown to foster fetal thalamocortical axonogenesis [76]. Thus, probiotic exposure during early stages of life, including in utero, may have preventative potential. In fact, one study in mice found that maternal supplementation of Lactococcus lactis (strain not disclosed) from 10.5 days of gestation increased blood vessel numbers and size in the cortical plate and cortical neurons density in offspring of both sexes at postnatal day 1, while the numbers of mitotic neural progenitor cells were increased in females only [77]. Interestingly, effects were investigated in the context of anxiety, which is known to appear early among psychiatric disorders [75]. At 10 weeks of age, females but not males from the above study had a higher activity level in bright zones and reduced fearful behavior [77]. Similarly, adolescent offspring, especially females, of rats that received Lactobacillus helveticus NS8 in late pregnancy spent more time in open spaces compared to controls [63]. No effects on cognition and behavior were seen in 11 years old children born at risk for allergic disease and exposed to Lacticaseibacillus rhamnosus HN001 or Bifidobacterium animalis subsp. lactis HN019 since late gestation and until 2 years of age [78]. Interestingly, these benefits of probiotics are also seen in the context of obesity. Administration of a multi-strain probiotic to mouse dams since conception prevented obesity-induced anxiety-like behavior in offspring at weaning and at adulthood in both sexes [79••]. Thus, findings from these recent pre-clinical studies suggest that maternal probiotic intake may reduce anxiety-like behavior in the next generation, potentially through modulation of neurodevelopment processes in utero and early life. Moreover, these studies suggest that effects may be sex-specific. Since psychiatric disorders manifest differently between sexes and are more prevalent and damaging in females compared to males [80], more studies should be conducted to understand if maternally administered probiotics hold potential for sex-targeted clinical applications.
Allergic Diseases
The effect of probiotic supplementation during prenatal and early life on prevention of allergic diseases has been extensively studied, leading to the release of recommendations for populations at risk [7]. These guidelines are the same for both sexes, and previous studies largely focused on Lactobacillus species, alone or in combination with Bifidobacterium. Recent literature has continued investigating the mechanisms behind probiotic preventative effects. Studies in mice show that probiotics, typically administered starting at mid gestation, act through immune-mediated mechanisms (details in Table 1), in both models of asthma [81] and atopic dermatitis [82], and these effects may be strain-specific [82].
Interestingly, studies in healthy women receiving probiotics from 36 weeks of gestation to 3 months of lactation showed a reduction in infant atopic dermatitis incidence, which was associated with decreased proportion of Th22 but independent from Th1/Th2 balance [83, 84]. A clinical study of women with a family history of treated allergic diseases receiving Limosilactobacillus reuteri ATCC 55730 during late pregnancy reported a modulation in DNA methylation of CD4 + T cells genes related to immune maturation and allergy development in infants at birth, suggesting that epigenetic modifications may mediate the preventative effects of probiotics in this context [85]. Further studies are needed to decipher the exact mechanisms. Long-term effects were also investigated in clinical studies. While combined maternal and infant supplementation with a probiotic mix (Lactobacillus salivarius CUL61, Lactobacillus paracasei CUL08, Bifidobacterium animalis subsp. lactis CUL34, Bifidobacterium bifidum CUL20) had no effects on asthma or eczema prevalence in 5-year-old children [86], the administration of another probiotic mix (Lacticaseibacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, Propionibacterium freudenreichii ssp. shermanii JS) or of Lacticaseibacillus rhamnosus HN001 to the mother and infant decreased the lifetime prevalence of eczema and atopic sensitization [87, 88] and food allergy [88] in 10- and 11-year-old children, respectively. Probiotic preventive effects on upper respiratory tract infections [88] and eczema [89] were also reported in populations subgroups of caesarean-delivered infants, after 10 and 13 years, respectively. Of importance, Lacticaseibacillus rhamnosus HN001 was found not to have the same effects on infant eczema, wheeze, and atopic sensitization when given to the mother alone without infant supplementation [87, 90•], thus calling for more studies investigating the timing of probiotic administration.
Metabolic Disorders
Maternal nutritional status is a determinant of offspring metabolic health and both pre-clinical and clinical studies demonstrate that various components of the metabolic syndrome are susceptible to fetal programming [91]. The study of maternal probiotics administration and effects on offspring metabolic health is still in its infancy, with most human studies focused solely on maternal outcomes [47,48,49, 92]. In pre-clinical studies, offspring have been evaluated at weaning and adulthood, with hypertension and risk for cardiovascular disease being the most studied conditions [93,94,95,96]. Interestingly, the only pre-clinical study that we found administering probiotic since pre-conception identified sex- and time-specific (weaning versus young adults) benefits in offspring and stronger evidence for reduced cardiovascular dysfunction in female offspring [93]. Most other pre-clinical studies have been conducted in males only (Table 1).
A study in normal-weight women supplemented with Lacticaseibacillus rhamnosus GG and Bifidobacterium lactis Bb-12 from the 4th week of pregnancy until birth showed a reduction in DNA methylation of obesity and weight gain-related genes in offspring, suggesting again that epigenetics might be a mechanism underlying probiotics programming effects [56•]. As pre-clinical studies revealed that significant weight differences are observable at weaning and adulthood, although males and females were not studied separately, it would be interesting to assess whether maternal probiotics effects on offspring growth are also observable during infancy and puberty, and in a sex-specific manner.
Intestinal Microbiota
Modulation of the microbiota is not a prerequisite for probiotics effects. In addition, resilience of an established gut microbiota makes it difficult to modify using exogenous microorganisms, though microbiota susceptibility is likely higher during early stages of plasticity. A recent meta-analysis found that maternal exposures including body mass index, drug-induced alteration of the microbiota, and probiotics administration influence the offspring intestinal microbiota [97]. In animal models, maternal probiotic supplementation had different effects on the offspring gut microbiota composition and structure, depending on the species administered and the time of administration [58, 59, 62, 69,70,71, 73••, 81, 82, 93, 95, 96, 98,99,100]. Different effects were also observed in various regions of the intestinal tract [69]. Interestingly, co-administration of probiotic Lactiplantibacillus plantarum B90 and Saccharomyces cerevisiae P11 with prebiotic xylooligosaccharides modified the probiotic effect on microbiota outcomes of piglets [69]. Probiotics with and without prebiotic increased Bacteroidetes and Bifidobacterium jejunal relative abundance, while only co-administration also increased Firmicutes and Lactobacillus [69]. Most human studies of maternally administered probiotics did not assess infant microbiota. For those that did, maternal probiotic intake was found to transiently increase the relative abundance of administered probiotic species or strain in the offspring [83, 101], regardless of the participants being healthy or at risk for allergic diseases (Table 2). Pre-clinical studies are also the only studies assessing microbial outcomes long-term, including effects on microbial diversity and/or composition at puberty in healthy mice [98] and mice born to dams exposed to an obesogenic diet [93], as well as at young adulthood [93, 95, 96]. Interestingly, some of these studies investigated microbiota outcomes in offspring of both sexes. This is relevant because there is evidence for sex-specific microbiota taxa as early as 2 weeks after birth [102], which likely become more pronounced during puberty [103]. Some of the probiotics studied showed sex-dependent effects on microbiota structure and taxa relative abundance [73••, 93]. This may be a result of hormonal interactions or of the offspring microbiota sex-driven effects. The latter is aligned with the finding that the infant baseline microbiota may determine the success of a maternal probiotic intervention aimed at preventing atopic dermatitis [83].
Notably, none of these studies used metagenomic approaches and thus it remains unknown if probiotics modulated microbial function. This is important because some pre-clinical studies found that microbial metabolites were altered in response to probiotics, including increased fecal short chain fatty acids in response to Lacticaseibacillus rhamnosus [62, 96] and decreased plasma trimethylamine N-oxide (TMAO) in response to Lacticaseibacillus casei [96]. Short-chain fatty acids such as acetate, propionate, and, in particular, butyrate are bacterial metabolites produced by fermentation of dietary fibers, and help maintain intestinal homeostasis [104]. TMAO is produced by liver oxidation of the intestinal microbial metabolite trimethylamine and is a marker of cardiovascular diseases [105]. It will be important for future studies to expand on these analyses to determine if programming effects of probiotics manifest at the functional level and to determine the quality and quantity of the microbial metabolites to which the host becomes exposed.
Conclusions
Here, we have reviewed recent pre-clinical and clinical studies investigating programming effects of maternally administered probiotics on offspring health. Studies published during the past 5 years expand on previous knowledge in the context of growth and gut health and additionally describe effects in the context of the metabolic syndrome and behavior (Fig. 1). Underlying mechanisms are also starting to be investigated. The study of probiotics in the context of DOHaD is in its infancy and it is not currently possible to make recommendations for clinical practice beyond allergic diseases. Pre-clinical studies are essential to investigate maternal programming effects of multiple outcomes in both male and female offspring in strictly controlled conditions and to elucidate molecular mechanisms. To encourage transparency and reproducibility of studies among research groups, it is important that these studies systematically report study details, including probiotic strain and dose along with timing and duration of probiotic exposure; the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines offer comprehensive recommendations for reporting [106].
Offspring health outcomes programmed by maternal probiotic intake started prenatally. Previous knowledge (until 2017) included growth, gut health and intestinal barrier, allergic diseases, and gut microbiota findings. In addition to these outcomes, recent studies described effects on metabolic disorders, and neurodevelopment and anxiety. Clinical and pre-clinical findings are indicated in bold and italics, respectively. Icons depict findings assessed in infants or animal models (mice, rats, rabbits, or pigs). Created with BioRender.com
While most clinical studies initiated the administration of probiotics towards the end of pregnancy and continued until 3 months of lactation, pre-clinical studies started at the beginning of pregnancy and continued until weaning. There are no studies that isolated the pregnancy period, and only one mouse and one clinical study began supplementation at pre-conception; it would be important to understand which are the windows of susceptibility for probiotics to positively affect the offspring. Offspring characteristics, including sex, can also play a role. The male sex is more susceptible to in utero programming [107] and different placental DNA methylation patterns have been observed for male and female infants [108]. Interestingly, four studies reviewed here proposed DNA methylation as an underlying mechanism for programming effects of probiotics [56•, 84, 100, 109•]. Effects could also be mediated by the microbiota, with preventative benefits in inflammation [73••]. Interestingly, a clinical study of probiotics administered during late pregnancy and lactation for the prevention of atopic dermatitis found that individual microbiota characteristics, in this case, representation of Bifidobacterium dentium, could determine the effects of the probiotic intervention [83]. It would be important to study the programming effects of probiotics in infants at risk for altered microbial maturation patterns, for example very low birth weight or malnourished infants. Microbial maturation continues throughout adolescence and studies have in fact found that probiotic effects might appear during puberty and adulthood [62, 87,88,89, 94,95,96]. Beyond allergy-related outcomes, current human studies report findings at birth or in infants up to 2 years of age; longer trials will provide a more comprehensive understanding of the programming potential of probiotics. Finally, the studies reviewed were performed in Northern Europe, Asia, and Oceania calling for more trials to be conducted in America and Africa and to encompass ethnically diverse populations.
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Funding
Work in the laboratory of EMC is supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) (Grant # RGPIN-2019–06100) and the Canadian Institutes of Health Research (CIHR). EMC was the recipient of the Lawson Family Chair in Microbiome Nutrition Research. SES was funded by NSERC Graduate Scholarships-Master’s (NSERC CGS M) and Ontario Graduate Scholarship (OGS).
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Cuinat, C., Stinson, S.E., Ward, W.E. et al. Maternal Intake of Probiotics to Program Offspring Health. Curr Nutr Rep 11, 537–562 (2022). https://doi.org/10.1007/s13668-022-00429-w
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DOI: https://doi.org/10.1007/s13668-022-00429-w