Host remodeling of the gut microbiome and metabolic changes during pregnancy.

Many of the immune and metabolic changes occurring during normal pregnancy also describe metabolic syndrome. Gut microbiota can cause symptoms of metabolic syndrome in nonpregnant hosts. Here, to explore their role in pregnancy, we characterized fecal bacteria of 91 pregnant women of varying prepregnancy BMIs and gestational diabetes status and their infants. Similarities between infant-mother microbiotas increased with children's age, and the infant microbiota was unaffected by mother's health status. Gut microbiota changed dramatically from first (T1) to third (T3) trimesters, with vast expansion of diversity between mothers, an overall increase in Proteobacteria and Actinobacteria, and reduced richness. T3 stool showed strongest signs of inflammation and energy loss; however, microbiome gene repertoires were constant between trimesters. When transferred to germ-free mice, T3 microbiota induced greater adiposity and insulin insensitivity compared to T1. Our findings indicate that host-microbial interactions that impact host metabolism can occur and may be beneficial in pregnancy.

Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.

The preterm gut microbiota and administration routes of different probiotics: a randomized controlled trial.

BACKGROUND: Preterm children with their aberrant gut microbiota and susceptibility to infections and inflammation constitute a considerable target group for probiotic therapy to generate the age-appropriate healthy microbiota. METHODS: 68 preterm neonates were randomized into five intervention groups: Beginning from the median age of 3 days, 13 children received Lactobacillus rhamnosus GG (LGG) directly orally, and 17 via the lactating mother. 14 children received LGG with Bifidobacterium lactis Bb-12 (Bb12) orally, and 10 via the lactating mother. 14 children received placebo. The children's faecal microbiota was assessed at the age of 7 days by 16S rRNA gene sequencing. RESULTS: The gut microbiota compositions of the children directly receiving the probiotic combination (LGG + Bb12) were significantly different from those of the children receiving the other intervention modes or placebo (p = 0.0012; PERMANOVA), the distinction being due to an increase in the relative abundance of Bifidobacterium animalis (P < 0.00010; ANCOM-BC), and the order Lactobacillales (P = 0.020; ANCOM-BC). CONCLUSION: The connection between aberrant primary gut microbiota and a heightened risk of infectious and non-communicable diseases invites effective microbiota modulation. We show that the direct, early, and brief probiotic intervention of LGG + Bb12 109 CFU each, is sufficient to modulate the gut microbiota of the preterm neonate. IMPACT: Preterm children have a higher risk of several health problems partly due to their aberrant gut microbiota. More research is needed to find a safe probiotic intervention to modify the gut microbiota of preterm children. The maternal administration route via breast milk might be safer for the newborn. In our study, the early and direct administration of the probiotic combination Lactobacillus rhamnosus GG with Bifidobacterium lactis Bb-12 increased the proportion of bifidobacteria in the preterm children's gut at the age of 7 days, but the maternal administration route was not as effective.

Early life exposures and development of allergic disease in infants with familial risk: Results from ongoing probiotic intervention trials.

AIM: We search revision of risk determinants of the ongoing allergy epidemic. METHODS: Children numbering 433 born to mothers with allergic disease or sensitisation were selected from the three ongoing probiotic intervention trials for this case-control study. Children who developed atopic eczema or food allergy, had positive skinprick test results or had been prescribed inhaled corticosteroids by the age of 2 years were identified as cases (n = 231), while children without allergic manifestations were the healthy controls (n = 202). The data on early environmental exposures were collected from prospectively documented study records. The statistical analyses were adjusted for potential confounders. RESULTS: Determinants associated with the increased risk of atopic eczema were lower maternal prepregnancy BMI (aOR 0.15, 95% CI: 0.037-0.54) and maternal intrapartum antibiotic treatment (aOR 2.21, 95% CI 1.20-4.10), the latter also linked to obstructive respiratory symptoms (aOR 3.87, 95% CI 1.07-14.06). The risk of allergic sensitisation was associated with lower maternal prepegnancy BMI (aOR 0.18, 95% CI 0.43-0.79) and intrapartum antibiotic treatment (aOR 2.13, 95% CI 1.07-4.22). CONCLUSION: Based on our demonstrations, interventions such as personalised diets, can be optimised for specific subgroups and definite risk periods.

Spontaneous preterm delivery is reflected in both early neonatal and maternal gut microbiota.

BACKGROUND: Aberrant gut microbiota composition in preterm neonates is linked to adverse health consequences. Little is known about the impact of perinatal factors or maternal gut microbiota on initial preterm gut colonization. METHODS: Fecal samples were collected from 55 preterm neonates (<35 gestational weeks), 51 mothers, and 25 full-term neonates during the first 3-4 postpartum days. Gut microbiota composition was assessed using 16S ribosomal RNA gene sequencing. RESULTS: Preterm neonates exhibited significantly lower gut microbiota alpha diversity and distinct beta diversity clustering compared to term neonates. Spontaneous preterm birth was associated with distinct initial gut microbiota beta diversity as compared to iatrogenic delivery. Gestational age or delivery mode had no impact on the preterm gut microbiota composition. The cause of preterm delivery was also reflected in the maternal gut microbiota composition. The contribution of maternal gut microbiota to initial preterm gut colonization was more pronounced after spontaneous delivery than iatrogenic delivery and not dependent on delivery mode. CONCLUSIONS: The initial preterm gut microbiota is distinct from term microbiota. Spontaneous preterm birth is reflected in the early neonatal and maternal gut microbiota. Transmission of gut microbes from mother to neonate is determined by spontaneous preterm delivery, but not by mode of birth. IMPACT: The initial gut microbiota in preterm neonates is distinct from those born full term. Spontaneous preterm birth is associated with changes in the gut microbiota composition of both preterm neonates and their mothers. The contribution of the maternal gut microbiota to initial neonatal gut colonization was more pronounced after spontaneous preterm delivery as compared to iatrogenic preterm delivery and not dependent on delivery mode. Our study provides new evidence regarding the early gut colonization patterns in preterm infants. Altered preterm gut microbiota has been linked to adverse health consequences and may provide a target for early intervention.

The Microbiota and Malnutrition: Impact of Nutritional Status During Early Life.

According to the developmental origins of health and disease hypothesis, our health is determined by events experienced in utero and during early infancy. Indeed, both our prenatal and postnatal nutrition conditions have an impact on the initial architecture and activity of our microbiota. Recent evidence has underlined the importance of the composition of the early gut microbiota in relation to malnutrition, whether it be undernutrition or overnutrition, that is, in terms of both stunted and overweight development. It remains unclear how early microbial contact is linked to the risk of disease, as well as whether alterations in the microbiome underlie the pathogenesis of malnutrition or are merely the end result of it, which indicates that thequestion of causality must urgently be answered. This review provides information on the complex interaction between the microbiota and nutrition during the first 1,000 days of life, taking into account the impact of both undernutrition and overnutrition on the microbiota and on infants' health outcomes in the short- and long-term.

Mycobiome Profiles in Breast Milk from Healthy Women Depend on Mode of Delivery, Geographic Location, and Interaction with Bacteria.

Recent studies report the presence of fungal species in breast milk of healthy mothers, suggesting a potential role in infant mycobiome development. In the present work, we aimed to determine whether the healthy human breast milk mycobiota is influenced by geographical location and mode of delivery, as well as to investigate its interaction with bacterial profiles in the same samples. A total of 80 mature breast milk samples from 4 different countries were analyzed by Illumina sequencing of the internal transcribed spacer 1 (ITS1) region, joining the 18S and 5.8S regions of the fungal rRNA region. Basidiomycota and Ascomycota were found to be the dominant phyla, with Malassezia and Davidiella being the most prevalent genera across countries. A core formed by Malassezia, Davidiella, Sistotrema, and Penicillium was shared in the milk samples from the different origins, although specific shifts in mycobiome composition were associated with geographic location and delivery mode. The presence of fungi in the breast milk samples was further confirmed by culture and isolate characterization, and fungal loads were estimated by quantitative PCR (qPCR) targeting the fungal ITS1 region. Cooccurrence network analysis of bacteria and fungi showed complex interactions that were influenced by geographical location, mode of delivery, maternal age, and pregestational body mass index. The presence of a breast milk mycobiome was confirmed in all samples analyzed, regardless of the geographic origin.IMPORTANCE During recent years, human breast milk has been documented as a potential source of bacteria for the newborn. Recently, we have reported the presence of fungi in breast milk from healthy mothers. It is well known that environmental and perinatal factors can affect milk bacteria; however, the impact on milk fungi is still unknown. The current report describes fungal communities (mycobiota) in breast milk samples across different geographic locations and the influence of the mode of delivery. We also provide novel insights on bacterium-fungus interactions, taking into account environmental and perinatal factors. We identified a core of four genera shared across locations, consisting of Malassezia, Davidiella, Sistotrema, and Penicillium, which have been reported to be present in the infant gut. Our data confirm the presence of fungi in breast milk across continents and support the potential role of breast milk in the initial seeding of fungal species in the infant gut.

Perinatal nutrition impacts on the functional development of the visual tract in infants.

BACKGROUND AND OBJECTIVE: We investigated the associations of maternal diet and serum fatty acids during pregnancy and in early infancy on infantile neurodevelopment. METHODS: Pattern-reversal visual evoked potentials (pVEP) as depictors of central nervous system maturation were recorded from 56 children when they were 2 years old. Maternal nutrient intakes were calculated from food diaries and fish consumption from questionnaires collected during pregnancy. Serum phospholipid fatty acids were determined by gas chromatography in late pregnancy and from infants at 1 month of age. RESULTS: The children of the women who consumed fish three or more times per week during the last trimester of pregnancy had a higher pVEP component P100 amplitude for 60' (mean 23.4, SD 8.1) and 30' (mean 20.4, SD 6.7) of arcminute check sizes compared to those who consumed fish 0-2 times per week (mean 15.0, SD 4.8, p = 0.023, adjusted for birth weight and gender p = 0.058 and mean 13.4, SD 2.0, respectively, p = 0.028, adjusted p = 0.072). Maternal and child serum phospholipid fatty acids correlated with child pVEP measurements. CONCLUSION: The results of this small-scale study suggest that fish consumption during pregnancy and perinatal serum fatty acid status may associate with neurodevelopment within visual system during infancy.

The impact of probiotic supplementation during pregnancy on DNA methylation of obesity-related genes in mothers and their children.

PURPOSE: Dietary supplementation with probiotics during pregnancy has been suggested to decrease the risk for obesity in women after delivery and to minimize excessive weight gain in their children. Epigenetic DNA methylation has been proposed to impact on gene activity, thereby providing a plausible molecular mechanism for a broad range of biological processes and diseases. This pilot study aimed to evaluate whether probiotic supplementation during pregnancy could modify the DNA methylation status of the promoters of obesity and weight gain-related genes in mothers and their children. METHODS: A sample of 15 pregnant women was taken from a prospective, randomized mother and infant nutrition and probiotic study. Seven women received the probiotic supplementation and eight served as controls. The women's and their children's DNA methylation status of obesity (623 genes) and weight gain-related (433) gene promoters were analyzed from blood samples at the mean of 9.8 months (range 6.1-12.7 months) postpartum. RESULTS: Probiotic supplementation led to significantly decreased levels of DNA methylation in 37 gene promoters and increased levels of DNA methylation in one gene promoter in women. In their children, 68 gene promoters were significantly affected consistently with a lower level of DNA methylation in the probiotic group. CONCLUSIONS: On the basis of our pilot study, we suggest that probiotic supplementation during pregnancy may affect the DNA methylation status of certain promoters of obesity and weight gain-related genes both in mothers and their children, thereby providing a potential mechanism for long-lasting health effects.

Dysbiosis in Snoring Children: An Interlink to Comorbidities?

BACKGROUND AND OBJECTIVES: Early microbial colonization has a key impact on infant health through nutritional, immunological, and metabolic programming. The origin of child snoring is multifactorial and complex, and may thereby also generate long-term health problems. The link between child snoring and gut microbes remains unclear, although indirect evidence exists regarding this relationship. This study aimed to characterize the connection between gut microbiota and child snoring. METHODS: In a prospective, observational CHILD-SLEEP birth cohort study, gut microbiota in a subcohort of 43 of these children at 2 years of life was profiled with 16S ribosomal RNA gene amplicon sequencing. RESULTS: A higher abundance of the Proteobacteria phylum, the Enterobacteriaceae family, and Erysipelotrichaceae family, as well as a higher ratio of Firmicutes to Bacteroidetes were detected in snorers as compared to controls. Furthermore, snorers showed significantly lower microbial diversity and richness than non-snorers. CONCLUSIONS: The snoring children manifest different gut microbiota as compared with healthy children. Considering that snoring and sleep disorders can be a source of long-term consequences, including cardiovascular, metabolic, immunological, neurocognitive and behavioral consequences, our results proposes early microbiota as a new treatment target.

Increase in serum Interleukin-10 does not alleviate pro-inflammatory MCP-1 production in obese pregnancies.

Maternal cytokine profiles during pregnancy are characterized by significant deviations, varying substantially between gestational time points and tissues. Obesity, in turn, is linked with low-grade inflammation in adipose tissue and increased concentrations of systemic inflammatory mediators. However, the balance of pro- and anti-inflammatory cytokines in obese pregnancy has remained elusive. In view of the demonstrations that the obesity is a global epidemic in the population at reproductive age with a strong intergenerational impact, we investigated the relation of gestational immune adaptations and obesity-induced inflammation. We found a significant decrease in systemic IL-1ß and MCP-1 concentration from 1st to 3rd trimester of pregnancy while IL-10 concentration increased, respectively. However, in obese pregnancies this reduction of pro-inflammatory mediators was not detected. This may constitute an additional risk factor in obese pregnancies in which the concentration of MCP-1 is already upregulated compared to normal weight mothers.

Long-term safety and efficacy of perinatal probiotic intervention: Evidence from a follow-up study of four randomized, double-blind, placebo-controlled trials.

BACKGROUND: Societies worldwide are faced with a progressive increase in immune-mediated health problems such as allergic, autoimmune, and inflammatory diseases, as well as obesity. Perinatal administration of specific probiotic bacteria is an attractive approach in reducing the risk of these conditions, but long-term efficacy and safety data are lacking. The aim here was to evaluate the clinical benefit and long-term safety of specific probiotics administered during the perinatal period. METHODS: The probiotic strains used were Lactobacillus rhamnosus GG, Bifidobacterium lactis Bb-12, Lactobacillus paracasei ST11, and Bifidobacterium longum BL999. The children involved have subsequently undergone prospective long-term follow-up. In addition to physical examination, data were collected by structured questionnaires on non-communicable diseases and continued probiotic use, and growth data from welfare clinics and school nurses. RESULTS: Altogether 303 mother-infant pairs were included in the analysis. Seventy-six of 163 (47%) children receiving perinatal probiotics had developed allergic disease compared with 79 of 140 (56%) receiving placebo (OR 0.67, 95% confidence intervals [CI] 0.43-1.06, p = 0.09). Fifty-nine of 133 (44%) children receiving L. rhamnosus GG perinatally had developed allergic disease, OR 0.62, 95% CI 0.38-0.99, p = 0.047, as compared to placebo. We found no differences in growth or non-communicable disease prevalence between children receiving perinatally probiotics or placebo. CONCLUSIONS: Perinatal probiotic administration is safe in long-term follow-up. Children receiving L. rhamnosus GG perinatally tended to have decreased allergy prevalence.

Infantile Colic Is Associated With Low-grade Systemic Inflammation.

OBJECTIVES: Dysbiosis, an imbalance in the taxonomic composition of the gut bacteria occurring during the critical stages of development, induces lasting shifts in the immunological and metabolic phenotype if accompanied by an inflammatory response. Because altered gut microbiota and successful treatment with probiotics have both been demonstrated in cases of colic, we hypothesized here that infants with colic might have low-grade inflammation. METHODS: In 28 infants with colic and in 12 healthy controls at the age of 1 month, we measured the following serum immunological biomarkers: cytokines interleukin 1ß (IL-1ß); IL-6; IL-10; tumor necrosis factor α; interferon γ (IFN-γ); chemokines IL-8; monocyte chemotactic protein-1 (MCP-1); macrophage inflammatory protein 1ß (MIP-1ß) and chemokine (C-X-C motif) ligand 16; and intestinal fatty acid-binding protein, a biomarker of enterocyte damage and zonulin, a biomarker of intestinal permeability. In addition, intestinal microbiota composition was correlated with immunological biomarkers. RESULTS: Infants with colic had increased concentrations of IL-8, MCP-1, and MIP-1ß in serum as compared with healthy children. All the other immunological biomarkers were comparable between the groups. Fecal levels of Clostridium leptum correlated negatively with the proinflammatory markers MCP-1 (r = -0.44, P = 0.02), MIP-1ß (r = -0.43, P = 0.02), and tumor necrosis factor α (r = -0.38, P = 0.04). In addition, C coccoides group levels correlated negatively with MCP-1 (r = -0.43, P = 0.02) and Bifidobacterium breve levels positively with chemokine (C-X-C motif) ligand 16 (r = 0.38, P = 0.04). CONCLUSIONS: In addition to gut microbiota alterations, colic in infants is associated with low-grade systemic inflammation. Specific bacterial species beyond conventional probiotics may have anti-inflammatory properties that may help to modulate microbiota and alleviate colic-related inflammation.

Breast Milk Polyamines and Microbiota Interactions: Impact of Mode of Delivery and Geographical Location.

BACKGROUND/AIMS: The aim of the present study was to identify and quantify the polyamine levels in human milk obtained from different countries and through different modes of delivery, and to investigate their association with breast milk microbes. METHODS: Mature breast milk samples were obtained from 78 healthy mothers after 1 month of lactation from 4 different geographical locations: Finland, Spain (Europe); South Africa (Africa); and China (Asia). Polyamines were determined using HPLC after dansyl derivatization and milk microbiota was obtained by 16S rRNA gene sequencing. RESULTS: The mean values of polyamines in breast milk were 70.0, 424.2, and 610.0 nmol/dL for putrescine, spermidine and spermine, respectively, and 1,170.9 nmol/dL of total polyamines. The levels of putrescine were significantly higher in Spain (p < 0.05) and spermidine levels were significantly higher in Finland (p < 0.05) compared with other countries. Cesarean delivery had an impact on polyamine levels and it was related to an increase in the putrescine concentration being significant in Spanish samples (p < 0.01). Furthermore, putrescine levels were correlated positively with Gammaproteobacteria (r = 0.46, p < 0.001), especially with Pseudomonas fragi (r = 0.40, p < 0.001). CONCLUSIONS: The results demonstrate significant effect of geographical variations in human milk polyamine concentrations, being correlated with human milk microbiota composition. These differences may have an impact on infant development during lactation.

Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in early childhood.

BACKGROUND: Specific probiotic bacteria have proven to be effective in the prevention and treatment of infectious diseases in early life in at-risk populations. The impact of administration of Bifidobacterium animalis subsp. lactis BB-12 (BB-12) on the risk of acute infectious diseases was studied in healthy children. METHODS: In this double-blind, placebo-controlled study, 109 1-mo-old infants were assigned randomly to a probiotic group receiving a BB-12-containing tablet (n = 55) or a placebo (n = 54). Test tablets were administered to the infants twice a day (daily dose of BB-12 10 billion colony-forming units) until the age of 2 y with a novel slow-release pacifier or a spoon. Breastfeeding habits, pacifier use, dietary habits, medications, and all signs and symptoms of acute infections were registered in diaries by parents and in questionnaires by trained professionals. RESULTS: The infants receiving BB-12 were reported to have experienced fewer respiratory tract infections (RTIs; 87 vs. 100%; risk ratio: 0.87; 95% confidence interval: 0.76, 1.00; P = 0.033) than the controls. No significant differences between the groups were observed in reported gastrointestinal symptoms, otitis media, or fever. The baseline characteristics of the two groups were similar, as was the duration of breastfeeding. CONCLUSION: Administration of BB-12 in early childhood may reduce RTIs.

Early Microbe Contact and Obesity Risk: Evidence Of Causality?

The industrialized societies worldwide are in the middle of epidemics of diet-related chronic diseases, obesity being the common denominator. Lately, these conditions have been linked with a distinct microbiota composition in affected individuals different from that of healthy individuals. In particular, dysbiosis during critical stages of development induces lasting alterations in the immune and metabolic phenotype. The compositional development of the gut microbiota, again, is highly sensitive to environmental influences such as maternal health and nutrition, the mode of delivery, early feeding and antibiotic use. Shifts in the microbiota by high-energy diet increase energy extraction and storage, provoke a low-grade inflammatory response and impair gut barrier function, and, consequently, result in obesity and metabolic disease. A lower abundance of butyrate-producing bacteria and lower overall richness of bacteria has been associated with increased metabolic disease risk in humans. Recent reports suggest that Akkermansia type bacteria or butyrate producing microbes may have anti-inflammatory potential and enhance intestinal barrier function, which may both alleviate obesity and related metabolic complications. Thus we are not directly what we eat or our mother eats, but what our microbiota eat and how the collective composition of the microbiome is modified by the diet. On this basis, altering the intestinal microecosystem may be taken as a key target to attain prophylactic or therapeutic effects in metabolic and inflammatory conditions. Tools for such modulation include specific probiotic bacteria and potentially also non-digestible carbohydrate components able to modify microbiota composition and activity.

Early Gut Colonization With Lactobacilli and Staphylococcus in Infants: The Hygiene Hypothesis Extended.

OBJECTIVES: The aim of the present study was to assess the mode of delivery and type-of-feeding impact on gut microbiota. We demonstrated higher fecal bifidobacteria in infants who were breast-fed (BF) or fed formula with prebiotics polydextrose (PDX) and galactooligosaccharides (GOS) versus formula without prebiotics. Here, we tested feces of that cohort for lactobacilli and Staphylococcus aureus, 2 types of bacteria present in breast milk. METHODS: In a double-blind, randomized study, 21- to 30-day-old term infants vaginally delivered and exclusively formula-fed received a cow's milk-based formula (control, n = 80) or the same formula with 4 g/L (1:1 ratio) of PDX/GOS (PDX/GOS, n = 77). A reference BF group (n = 71) was included. Stool samples were obtained at baseline and after 30 and 60 days of feeding to assess fecal bacteria by quantitative real-time polymerase chain reaction. RESULTS: Pairwise comparisons between baseline-adjusted means log10 colony-forming unit per gram feces of total lactobacilli counts (8.37 in control, 8.46 in PDX/GOS, and 8.42 in BF) showed a significant difference only between PDX/GOS and control at 30 and 60 days combined (P = 0.035), utilizing generalized estimating equations method. Baseline-adjusted odds ratio (OR) of colonization with S aureus was lower in control (OR 0.47, 95% confidence interval 0.22-1.00, P = 0.049) and PDX/GOS (OR 0.44, 95% confidence interval 0.21-0.94, P = 0.03) groups versus the BF group. CONCLUSIONS: Bacteria found in breast milk, such as lactobacilli and S aureus can also be found in infant feces. S aureus, traditionally considered harmful, may aid in educating the coevolving immune system. Modifying formula by adding prebiotics may bring gut microbiota closer to that of BF infants in terms of beneficial microbes.

Could obesity be an infectious disease?

The accomplishments in combating the obesity epidemic have thus far been insufficient. Indeed, the background to the increase in overweight and obesity is more complex than is generally anticipated. Recent scientific data suggest that the gut microbiota affects two main causes of obesity: energy harvest and storage from the diet, thereby increasing energy efficiency, and low-grade inflammatory response and impairment of gut barrier function. Consequently, considerable research interest is currently focusing on characterizing and manipulating the gut microbiota in attempt to reverse the intergenerational progression of obesity and its comorbidities. The proof of causality requires clinical interventions in well-characterized populations and documentation of the mechanisms.

Gut microbiota: a source of novel tools to reduce the risk of human disease?

Modern civilization is faced with a progressive increase in immune-mediated or inflammatory health problems such as allergic disease, autoimmune disorders, and obesity. An extended version of the hygiene hypothesis has been introduced to emphasize the intimate interrelationship among diet, the immune system, microbiome, and origins of human disease: the modern infant, particularly when delivered by cesarean section and without the recommended exclusive breastfeeding, may lack sufficient stimulation of the mucosal immune system to generate a tolerogenic immune milieu and instead be prone to develop chronic inflammatory conditions. These deviations may take the form of allergic or autoimmune disease, or predispose the child to higher weight gain and obesity. Moreover, evidence supports the role of first microbial contacts in promoting and maintaining a balanced immune response in early life and recent findings suggest that microbial contact begins prior to birth and is shaped by the maternal microbiota. Maternal microbiota may prove to be a safe and effective target for interventions decreasing the risk of allergic and noncommunicable diseases in future generations. These results support the hypothesis that targeting early interaction with microbes might offer an applicable strategy to prevent disease.

Probiotic Lactobacillus rhamnosus GG therapy and microbiological programming in infantile colic: a randomized, controlled trial.

BACKGROUND: Probiotic Lactobacillus reuteri and reduced allergen load may lessen the daily crying of colic infants, but the role of Lactobacillus rhamnosus GG (LGG) has remained obscure. METHODS: Infants with colic (n = 30) were enrolled during the first 6 wk of life. All families received behavioral support and allergen avoidance diet: breastfeeding mothers followed cow's milk elimination diet and formula-fed infants received extensively hydrolyzed casein formula. The randomized, double-blind intervention employed of LGG 4.5 × 10(9) cfu/d or placebo for a 4-wk study period. Daily crying was recorded by diaries and parental interviews. Fecal calprotectin and gut microbiota composition by quantitative PCR were evaluated before and after the intervention. RESULTS: Daily crying time was comparable between the probiotic (173 min) and the placebo group (174 min; P = 0.99) at the end of the intervention according to the parental diary. However, parents reported a decrease of 68% (95% confidence interval (CI): 58-78) in daily crying in the probiotic and 49% (95% CI: 32-66) in the placebo group (P = 0.05). CONCLUSION: LGG in infants treated in tandem with behavioral support and a cow's milk elimination diet did not provide additional treatment effect for diary-verified colic crying although parental report of crying suggested the probiotic intervention effective.