Digestive Tolerance and Safety of an Anti-Regurgitation Formula Containing Locust Bean Gum, Prebiotics and Postbiotics: A Real-World Study.

Purpose: Infant regurgitation is associated with other functional gastrointestinal disorders and signs and symptoms that have a major impact on the quality of life of infants and their families. This study evaluated the safety, tolerance, and real-world effectiveness of an anti-regurgitation formula containing locust bean gum (LBG), prebiotics, and postbiotics to alleviate digestive symptoms beyond regurgitation. Methods: This 3-month study involved infants with regurgitation requiring the prescription of an anti-regurgitation formula according to usual clinical practice. Outcomes included evaluation of the evolution of stool consistency and frequency; occurrence of colic, constipation, and diarrhea; and assessment of regurgitation severity. Infant crying, parental assessment of infant well-being, and parental satisfaction with the stool consistency were also evaluated. Results: In total, 190 infants (average age: 1.9±1.1 months) were included. After three months, stool frequency and consistency remained within the normal physiological range, with 82.7% of infants passing one or two stools per day and 90.4% passing loose or formed stools. There was no significant increase in the number of infants with diarrhea, whereas a decrease was observed in the number of infants with constipation after 1 month (p=0.001) and with colic after both 1 and 3 months (p<0.001). Regurgitation severity and crying decreased and parental satisfaction with stool consistency, formula acceptability, infant well-being, and sleep quality increased. Monitoring of adverse events did not reveal any safety concerns. Conclusion: Formulas containing LBG, prebiotics, and postbiotics were well tolerated and provided an effective strategy for managing infant regurgitation and gastrointestinal discomfort.

Safety and Tolerance of a Novel Anti-Regurgitation Formula: A Double-Blind, Randomized, Controlled Trial.

OBJECTIVES: A novel anti-regurgitation (AR) formula has been designed to support gut health and improve gastrointestinal (GI) symptoms beyond regurgitation. This study assessed the tolerance and safety of this new AR formula. METHODS: This was a 4-week double-blind, randomized, controlled trial with a 4-week extension in formula-fed infants with regurgitation. The new AR (Test) formula contained 0.4 g/100 mL locust bean gum (LBG) as thickener, partly fermented formula with postbiotics, and short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS) (0.4 g/100 mL, ratio 9:1). The Control AR formula contained LBG (0.4 g/100 mL) with postbiotics and has a history of safe use. The primary outcome was the Infant Gastrointestinal Symptom Questionnaire (IGSQ) sum score including stooling, spitting-up/vomiting, crying, fussiness and flatulence. RESULTS: All 182 infants screened were enrolled in the study. The primary analysis showed the equivalence of the IGSQ sum scores at Week 4 between groups. IGSQ sum scores improved significantly within 1 week (Mixed Model Repeated Measurement [MMRM], P < 0.001). Post-hoc analyses showed a bigger improvement of the IGSQ score in the Test (n = 38) versus Control (n = 44) group (MMRM, P = 0.008) in infants with more severe gastrointestinal (GI) symptoms (IGSQ score ≥35). Stool characteristics were comparable between groups. Growth related z scores were in line with the WHO child growth standards and both groups showed improvement of regurgitation. Adverse events did not show any safety concerns. CONCLUSIONS: The novel AR formula combining LBG, scGOS/lcFOS and postbiotics is well-tolerated, safe and supports adequate growth during the intervention. Post-hoc analyses suggest that the formula results in more improvement of GI symptom burden in infants with more severe symptoms.

Fermented infant formula (with Bifidobacterium breve C50 and Streptococcus thermophilus O65) with prebiotic oligosaccharides is safe and modulates the gut microbiota towards a microbiota closer to that of breastfed infants.

BACKGROUND & AIMS: Microbiome-modulators can help positively steer early-life microbiota development but their effects on microbiome functionality and associated safety and tolerance need to be demonstrated. We investigated the microbiome impact of a new combination of bioactive compounds, produced by the food-grade microorganisms Bifidobacterium breve C50 and Streptococcus thermophilus ST065 during a fermentation process, and prebiotics in an infant formula. Tolerance and safety were also assessed. METHODS: An exploratory prospective, randomized, double-blind, controlled, multi-centre study was designed to investigate the effect of bioactive compounds and prebiotics (short-chain galacto-oligosaccharides (scGOS)/long-chain fructo-oligosaccharides (lcFOS) 9:1). Experimental formulas containing these bioactive compounds and prebiotics (FERM/scGOS/lcFOS), prebiotics (scGOS/lcFOS), or bioactive compounds (FERM), were compared to a standard cow's milk-based control formula (Control). Exclusively breastfed infants were included as a reference arm since exclusive breastfeeding is considered as the optimal feeding for infants. The study lasted six months and included visits to health care professionals at baseline, two, four and six months of age. Stool SIgA concentration was the primary study outcome parameter. RESULTS: There were 280 infants randomized over the experimental arms and 70 infants entered the breastfed-reference arm. Demographics were balanced, growth and tolerance parameters were according to expectation and adverse events were limited. At four months of age the median SIgA concentration in the FERM/scGOS/lcFOS group was significantly higher compared to the Control group (p = 0.03) and was more similar to the concentrations found in the breastfed-reference group. Bifidobacterium increased over time in all groups. The FERM/scGOS/lcFOS combination resulted in a microbiota composition and metabolic activity closer to the breastfed infants' microbiome. CONCLUSION: The FERM/scGOS/lcFOS combination showed a significant positive effect on SIgA levels. All formulas tested were associated with normal growth and were well-tolerated. Additionally, at four months of age the FERM/scGOS/lcFOS formula brought the microbiome composition and metabolic activity closer towards that of breastfed infants. CLINICAL TRIAL REGISTRY: Registration number NTR2726 (Netherlands Trial Register; www.trialregister.nl/).

Effectiveness and Tolerance of a Locust Bean Gum-Thickened Formula: A Real-Life Study.

PURPOSE: Thickened infant formulas reduce regurgitation frequency and volume. Because the digestive tolerance of locust bean gum-containing formulas is controversial, the effectiveness and tolerance of a locust bean gum-thickened formula in infants presenting with regurgitation was evaluated. No other interventions were allowed during the 1 month follow-up period. METHODS: We conducted an open, prospective, observational study of a locust bean gum-thickened formula administered to infants presenting with moderate to severe regurgitation according to parents during 1 month. Effectiveness and tolerance were assessed by evaluating gastrointestinal symptoms and quality of life indicators. RESULTS: A total of 2,604 infants with an average age of 9.3±4.3 weeks were included in this 1 month trial. Regurgitation frequency and estimated volume decreased significantly (p<0.001) and the episodes were resolved completely in 48% of the infants. A significant decrease in duration of crying and episodes of gas (p<0.001), with improvement in quality of life parameters, was observed. Stool frequency increased and stool consistency softened (p<0.001) to levels within the physiologic range, consistent with the increased fiber load (0.42 g/100 mL). CONCLUSION: Locust bean gum-thickened formula decreased infant regurgitation, was well tolerated, and improved parental quality of life. Stool composition and frequency of the infants remained within the physiologic range.

Increased Susceptibility to Obesity and Glucose Intolerance in Adult Female Rats Programmed by High-Protein Diet during Gestation, But Not during Lactation.

Fetal and early postnatal nutritional environments contribute to lifelong health. High-protein (HP) intake in early life can increase obesity risk in response to specific feeding conditions after weaning. This study investigated the effects of a maternal HP diet during pregnancy and/or lactation on the metabolic health of offspring. Three groups of dams received a normal-protein (NP, 20E% proteins) diet during gestation and lactation (Control group), an HP diet (55E% proteins) during gestation (HPgest group), or an HP diet during lactation (HPlact group). From weaning until 10 weeks, female pups were exposed to the NP, the HP or the western (W) diet. HPgest pups had more adipocytes (p = 0.009), more subcutaneous adipose tissue (p = 0.04) and increased expression of genes involved in liver fatty acid synthesis at 10 weeks (p < 0.05). HPgest rats also showed higher food intake and adiposity under the W diet compared to the Control and HPlact rats (p ≤ 0.04). The post-weaning HP diet reduced weight (p < 0.0001), food intake (p < 0.0001), adiposity (p < 0.0001) and glucose tolerance (p < 0.0001) compared to the NP and W diets; this effect was enhanced in the HPgest group (p = 0.04). These results show that a maternal HP diet during gestation, but not lactation, leads to a higher susceptibility to obesity and glucose intolerance in female offspring.

Multiple functional gastrointestinal disorders are frequent in formula-fed infants and decrease their quality of life.

AIM: This prospective study evaluated the incidence of functional gastrointestinal disorders (FGIDs) during infancy, on their own or combined with other symptoms. METHODS: We asked 273 French paediatricians with a specific interest in FGIDs to provide feedback on 2757 infants aged zero to six months from March 2013 to January 2014. Gastrointestinal health status was assessed by two questionnaires at inclusion and at a four-week follow-up visit. FGIDs were assessed according to the Rome III criteria and quality of life (QoL) was monitored. RESULTS: Combined FGIDs were diagnosed in 2145 (78%) infants: 63% with two disorders and 15% with three or more disorders. The most frequently combined FGIDs were gas/bloating and colic (28%), colic and regurgitation (17.0%) and gas/bloating and regurgitation (8%). Compared to infants with a single FGID, combined FGID were associated with lower body weight (4.63 vs 4.79 kg, p = 0.009), shorter breastfeeding duration (33 vs 43 days, p < 0.001), a decreased QoL score (5.9 vs 6.5, p < 0.001), more frequent drug prescriptions (25% vs 13%, p < 0.001) and significantly greater improvements in QoL scores after four weeks (p = 0.003). CONCLUSION: Combined FGIDs were extremely common in infants up to six months of age and had a negative impact on breastfeeding, weight gain and QoL.

Specific synbiotics in early life protect against diet-induced obesity in adult mice.

AIMS: The metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health throughout life. Here, we determined how beneficial microbiome interventions in early life affect metabolic health in adulthood. METHODS: Postnatal diets were supplemented with either prebiotics (scGOS/lcFOS) or synbiotics (scGOS/lcFOS with Bifidobacterium breve M-16 V) until post-natal (PN) day 42 in a well-established rodent model for nutritional programming. Mice were subsequently challenged with a high-fat Western-style diet (WSD) for 8 weeks. Body weight and composition were monitored, as was gut microbiota composition at PN21, 42 and 98. Markers of glucose homeostasis, lipid metabolism and host transcriptomics of 6 target tissues were determined in adulthood (PN98). RESULTS: Early life synbiotics protected mice against WSD-induced excessive fat accumulation throughout life, replicable in 2 independent European animal facilities. Adult insulin sensitivity and dyslipidaemia were improved and most pronounced changes in gene expression were observed in the ileum. We observed subtle changes in faecal microbiota composition, both in early life and in adulthood, including increased abundance of Bifidobacterium. Microbiota transplantation using samples collected from synbiotics-supplemented adolescent mice at PN42 to age-matched germ-free recipients did not transfer the beneficial phenotype, indicating that synbiotics-modified microbiota at PN42 is not sufficient to transfer long-lasting protection of metabolic health status. CONCLUSION: Together, these findings show the potential and importance of timing of synbiotic interventions in early life during crucial microbiota development as a preventive measure to lower the risk of obesity and improve metabolic health throughout life.

High-Protein Exposure during Gestation or Lactation or after Weaning Has a Period-Specific Signature on Rat Pup Weight, Adiposity, Food Intake, and Glucose Homeostasis up to 6 Weeks of Age.

BACKGROUND: Early-life nutrition has a programming effect on later metabolic health; however, the impact of exposure to a high-protein (HP) diet is still being investigated. OBJECTIVE: This study evaluated the consequences on pup phenotype of an HP diet during gestation and lactation and after weaning. METHODS: Wistar rat dams were separated into 2 groups fed an HP (55% protein) or normal protein (NP) (control; 20% protein) isocaloric diet during gestation, and each group subsequently was separated into 2 subgroups that were fed an HP or NP diet during lactation. After weaning, male and female pups from each mother subgroup were separated into 2 groups that were fed either an NP or HP diet until they were 6 wk old. Measurements included weight, food intake, body composition, blood glucose, insulin, glucagon, leptin, insulin-like growth factor I, and lipids. RESULTS: Feeding mothers the HP diet during gestation or lactation induced lower postweaning pup weight (gestation diet × time, P < 0.0001; lactation diet × time, P < 0.0001). Regardless of dams' diets, pups receiving HP compared with NP diet after weaning had 7% lower weight (NP, 135.0 ± 2.6 g; HP, 124.4 ± 2.5 g; P < 0.0001), 16% lower total energy intake (NP, 777 ± 14 kcal; HP, 649 ± 13 kcal; P < 0.0001) and 31% lower adiposity (P < 0.0001). Pups receiving HP compared with NP diet after weaning had increased blood glucose, insulin, and glucagon when food deprived (P < 0.0001 for all). The HP compared with the NP diet during gestation induced higher blood glucose in food-deprived rats (NP, 83.2 ± 2.1 mg/dL; HP, 91.2 ± 2.1 mg/dL; P = 0.046) and increased plasma insulin in fed pups receiving the postweaning NP diet (gestation diet × postweaning diet, P = 0.02). CONCLUSION: Increasing the protein concentration of the rat dams' diet during gestation, and to a lesser extent during lactation, and of the pups' diet after weaning influenced pup phenotype, including body weight, fat accumulation, food intake, and glucose tolerance at 6 wk of age.

Preweaning modulation of intestinal microbiota by oligosaccharides or amoxicillin can contribute to programming of adult microbiota in rats.

OBJECTIVE: Increasing evidence suggests that early nutrition has programming effects on adult health. Identifying mechanisms underlying nutritional programming would aid in the design of new disease prevention strategies. The intestinal microbiota could be a key player in this programming because it affects host metabolic homeostasis, postnatal gut colonization is sensitive to early nutrition, and initial microbial set-up is thought to shape microbiota composition for life. The aim of this study was to determine whether early manipulation of intestinal microbiota actually programs adult microbiota in rats. METHODS: Suckling rats pups were supplemented with fructo-oligosaccharides, galacto-oligosaccharides/long-chain fructan mix (GOS/lcF, 9/1), acidic oligosaccharides, amoxicillin, or vehicle from the fifth to the fourteenth day of life, and weaned to standard chow at day 21. Ceco-colonic microbiota was characterized at 14 and 131 d by real-time polymerase chain reaction analysis. RESULTS: At day 14, all treatments affected microbiota. Amoxicillin had the most significant effect. All oligosaccharides decreased Firmicutes levels, whereas only fructo-oligosaccharides and GOS/lcF increased bifidobacteria. At day 131, most of these effects had faded away but a significant, albeit minor, adult microbiota programming was observed for rats that received GOS/lcF mix before weaning, regarding Roseburia intestinalis cluster, one subdivision of the Erysipelotrichaceae family as well as butyrate kinase gene. CONCLUSIONS: As revealed by a targeted quantitative polymerase chain reaction approach, programming of adult intestinal microbiota seems to vary according to the nature of the preweaning microbiotal modulator. This suggests that intestinal microbiota may, only under specific circumstances, serve as a relay of neonatal nutrition and thus potentially contribute to nutritional programming of host physiology.

Changes of the human gut microbiome induced by a fermented milk product.

The gut microbiota (GM) consists of resident commensals and transient microbes conveyed by the diet but little is known about the role of the latter on GM homeostasis. Here we show, by a conjunction of quantitative metagenomics, in silico genome reconstruction and metabolic modeling, that consumption of a fermented milk product containing dairy starters and Bifidobacterium animalis potentiates colonic short chain fatty acids production and decreases abundance of a pathobiont Bilophila wadsworthia compared to a milk product in subjects with irritable bowel syndrome (IBS, n = 28). The GM changes parallel improvement of IBS state, suggesting a role of the fermented milk bacteria in gut homeostasis. Our data challenge the view that microbes ingested with food have little impact on the human GM functioning and rather provide support for beneficial health effects.

The first thousand days - intestinal microbiology of early life: establishing a symbiosis.

The development of the intestinal microbiota in the first years of life is a dynamic process significantly influenced by early-life nutrition. Pioneer bacteria colonizing the infant intestinal tract and the gradual diversification to a stable climax ecosystem plays a crucial role in establishing host-microbe interactions essential for optimal symbiosis. This colonization process and establishment of symbiosis may profoundly influence health throughout life. Recent developments in microbiologic cultivation-independent methods allow a detailed view of the key players and factors involved in this process and may further elucidate their roles in a healthy gut and immune maturation. Aberrant patterns may lead to identifying key microbial signatures involved in developing immunologic diseases into adulthood, such as asthma and atopic diseases. The central role of early-life nutrition in the developmental human microbiota, immunity, and metabolism offers promising strategies for prevention and treatment of such diseases. This review provides an overview of the development of the intestinal microbiota, its bidirectional relationship with the immune system, and its role in impacting health and disease, with emphasis on allergy, in early life.

Altered gut microbiota and activity in a murine model of autism spectrum disorders.

Autism spectrum disorder (ASD) is a heterogeneous group of complex neurodevelopmental disorders with evidence of genetic predisposition. Intestinal disturbances are reported in ASD patients and compositional changes in gut microbiota are described. However, the role of microbiota in brain disorders is poorly documented. Here, we used a murine model of ASD to investigate the relation between gut microbiota and autism-like behaviour. Using next generation sequencing technology, microbiota composition was investigated in mice in utero exposed to valproic acid (VPA). Moreover, levels of short chain fatty acids (SCFA) and lactic acid in caecal content were determined. Our data demonstrate a transgenerational impact of in utero VPA exposure on gut microbiota in the offspring. Prenatal VPA exposure affected operational taxonomic units (OTUs) assigned to genera within the main phyla of Bacteroidetes and Firmicutes and the order of Desulfovibrionales, corroborating human ASD studies. In addition, OTUs assigned to genera of Alistipes, Enterorhabdus, Mollicutes and Erysipelotrichalis were especially associated with male VPA-exposed offspring. The microbial differences of VPA in utero-exposed males deviated from those observed in females and was (i) positively associated with increased levels of caecal butyrate as well as ileal neutrophil infiltration and (ii) inversely associated with intestinal levels of serotonin and social behaviour scores. These findings show that autism-like behaviour and its intestinal phenotype is associated with altered microbial colonization and activity in a murine model for ASD, with preponderance in male offspring. These results open new avenues in the scientific trajectory of managing neurodevelopmental disorders by gut microbiome modulation.

Intestinal microbiology in early life: specific prebiotics can have similar functionalities as human-milk oligosaccharides.

Human milk is generally accepted as the best nutrition for newborns and has been shown to support the optimal growth and development of infants. On the basis of scientific insights from human-milk research, a specific mixture of nondigestible oligosaccharides has been developed, with the aim to improve the intestinal microbiota in early life. The mixture has been extensively studied and has been shown to be safe and to have potential health benefits that are similar to those of human milk. The specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides has been found to affect the development of early microbiota and to increase the Bifidobacterium amounts as observed in human-milk-fed infants. The resulting gut ecophysiology is characterized by high concentrations of lactate, a slightly acidic pH, and specific short-chain fatty acid profiles, which are high in acetate and low in butyrate and propionate. Here, we have summarized the main findings of dietary interventions with these specific oligosaccharides on the gut microbiota in early life. The gut ecophysiology in early life may have consequences for the metabolic, immunologic, and even neurologic development of the child because reports increasingly substantiate the important function of gut microbes in human health. This review highlights major findings in the field of early gut colonization and the potential impact of early nutrition in healthy growth and development.

Influence of fermented milk products, prebiotics and probiotics on microbiota composition and health.

The gut microbiota is a highly diverse and relative stabile ecosystem increasingly recognized for its impact on human health. The homeostasis of microbes and the host is also referred to as eubiosis. In contrast, deviation from the normal composition, defined as dysbiosis, is often associated with localized diseases such as inflammatory bowel disease or colonic cancer, but also with systemic diseases like metabolic syndrome and allergic diseases. Modulating a gut microbiota dysbiosis with nutritional concepts may contribute to improving health status, reducing diseases or disease symptoms or supporting already established treatments. The gut microbiota can be modulated by different nutritional concepts, varying from specific food ingredients to complex diets or by the ingestion of particular live microorganisms. To underpin the importance of bacteria in the gut, we describe molecular mechanisms involved in the crosstalk between gut bacteria and the human host, and review the impact of different nutritional concepts such as pre-, pro- and synbiotics on the gastrointestinal ecosystem and their potential health benefits. The aim of this review is to provide examples of potential nutritional concepts that target the gut microbiota to support human physiology and potentially health outcomes.

Can antibiotic treatment in preweaning rats alter body composition in adulthood?

BACKGROUND: It is suggested that antibiotherapy in infancy might program adult body composition and thus could be a determinant of obesity risk. Although not convincingly substantiated by existing literature, this assumption is plausible since antibiotics affect intestinal microbiota, whose composition in adulthood is potentially programmable during infancy and which is able to interact with both fat development and central control of appetite. OBJECTIVES: In order to substantiate the link between antibiotherapy and programming of adult body composition, the present study investigated the impact of a course of amoxicillin treatment in neonatal period on subsequent growth and body composition in rats. METHODS: Suckling rat pups were treated by oral gavage with an amoxicillin solution (150 mg·kg(-1)) or vehicle from postnatal day (PND)5 to PND15. All animals were fully weaned at PND21 then fed a standard diet until PND130. Animal growth and food intake were followed up until PND130, when body composition and plasma leptin were measured. Faecal microbiota was typified at regular intervals using real-time quantitative polymerase chain reaction. RESULTS: Preweaning amoxicillin treatment affected the composition of the faecal microbiota of pups at PND21 but this impact did not sustain long beyond the antibiotic supplementation. Immediately after weaning, a transient increase in food intake (+11%) was noticed in amoxicillin-treated animals. However, no significant impact on either growth or body composition at adulthood was observed. CONCLUSIONS: In a neonatal animal model there is no evidence of a programming of adult body weight and composition by wide-spectrum antibiotic treatment in early life.

Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome.

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 µmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).

The early settlers: intestinal microbiology in early life.

The human intestinal microbiota forms an integral part of normal human physiology, and disturbances of the normal gut microbiology have been implicated in many health and disease issues. Because newborns are essentially sterile, their microbiota must establish and develop from the very first days of life. The first colonizers play an important role in the development of the ecosystem and may impact the long-term composition and activity of the microbiota. These first settlers obviously develop and proliferate dependent on host characteristics and diet, but other factors can also significantly contribute to this vital biological process. Considering the importance of the microbiota for the human immune, metabolic, and neurological systems, it is important to understand the dynamics and driving determinants of this development. This review gives a global overview of our current understanding of the different factors impacting the intestinal microbiology in early life.

Development of the Digestive System-Experimental Challenges and Approaches of Infant Lipid Digestion.

At least during the first 6 months after birth, the nutrition of infants should ideally consist of human milk which provides 40-60 % of energy from lipids. Beyond energy, human milk also delivers lipids with a specific functionality, such as essential fatty acids (FA), phospholipids, and cholesterol. Healthy development, especially of the nervous and digestive systems, depends fundamentally on these. Epidemiological data suggest that human milk provides unique health benefits during early infancy that extend to long-lasting benefits. Preclinical findings show that qualitative changes in dietary lipids, i.e., lipid structure and FA composition, during early life may contribute to the reported long-term effects. Little is known in this respect about the development of digestive function and the digestion and absorption of lipids by the newborn. This review gives a detailed overview of the distinct functionalities that dietary lipids from human milk and infant formula provide and the profound differences in the physiology and biochemistry of lipid digestion between infants and adults. Fundamental mechanisms of infant lipid digestion can, however, almost exclusively be elucidated in vitro. Experimental approaches and their challenges are reviewed in depth.

The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins.

Understanding how the human gut microbiota and host are affected by probiotic bacterial strains requires carefully controlled studies in humans and in mouse models of the gut ecosystem where potentially confounding variables that are difficult to control in humans can be constrained. Therefore, we characterized the fecal microbiomes and metatranscriptomes of adult female monozygotic twin pairs through repeated sampling 4 weeks before, 7 weeks during, and 4 weeks after consumption of a commercially available fermented milk product (FMP) containing a consortium of Bifidobacterium animalis subsp. lactis, two strains of Lactobacillus delbrueckii subsp. bulgaricus, Lactococcus lactis subsp. cremoris, and Streptococcus thermophilus. In addition, gnotobiotic mice harboring a 15-species model human gut microbiota whose genomes contain 58,399 known or predicted protein-coding genes were studied before and after gavage with all five sequenced FMP strains. No significant changes in bacterial species composition or in the proportional representation of genes encoding known enzymes were observed in the feces of humans consuming the FMP. Only minimal changes in microbiota configuration were noted in mice after single or repeated gavage with the FMP consortium. However, RNA-Seq analysis of fecal samples and follow-up mass spectrometry of urinary metabolites disclosed that introducing the FMP strains into mice results in significant changes in expression of microbiome-encoded enzymes involved in numerous metabolic pathways, most prominently those related to carbohydrate metabolism. B. animalis subsp. lactis, the dominant persistent member of the FMP consortium in gnotobiotic mice, up-regulates a locus in vivo that is involved in the catabolism of xylooligosaccharides, a class of glycans widely distributed in fruits, vegetables, and other foods, underscoring the importance of these sugars to this bacterial species. The human fecal metatranscriptome exhibited significant changes, confined to the period of FMP consumption, that mirror changes in gnotobiotic mice, including those related to plant polysaccharide metabolism. These experiments illustrate a translational research pipeline for characterizing the effects of FMPs on the human gut microbiome.

Transmission of intestinal Bifidobacterium longum subsp. longum strains from mother to infant, determined by multilocus sequencing typing and amplified fragment length polymorphism.

The gastrointestinal tracts of neonates are colonized by bacteria immediately after birth. It has been discussed that the intestinal microbiota of neonates includes strains transferred from the mothers. Although some studies have indicated possible bacterial transfer from the mother to the newborn, this is the first report confirming the transfer of bifidobacteria at the strain level. Here, we investigated the mother-to-infant transmission of Bifidobacterium longum subsp. longum by genotyping bacterial isolates from the feces of mothers before delivery and of their infants after delivery. Two hundred seven isolates from 8 pairs of mothers and infants were discriminated by multilocus sequencing typing (MLST) and amplified fragment length polymorphism (AFLP) analysis. By both methods, 11 strains of B. longum subsp. longum were found to be monophyletic for the feces of the mother and her infant. This finding confirms that these strains were transferred from the intestine of the mother to that of the infant. These strains were found in the first feces (meconium) of the infant and in the feces at days 3, 7, 30, and 90 after birth, indicating that they stably colonize the infant's intestine immediately after birth. The strains isolated from each family did not belong to clusters derived from any of the other families, suggesting that each mother-infant pair might have unique family-specific strains.