Scientific References

Probiotics have been shown to enhance specific immune responses to vaccines. We aim to assess the effect of probiotic supplementation on specific IgG antibody responses to Hepatitis B (HepB) vaccination in infants. Compared to controls, probiotic supplementation improved HepB surface antibody responses in subjects receiving monovalent doses of HepB vaccine at 0, 1 month and a DTPa–HepB combination vaccine at 6 months [placebo (n=28): 187.97 (180.70–195.24), probiotic (n = 29): 345.70 (339.41–351.99) mIU/ml] (p = 0.069), but not those who received 3 monovalent doses [placebo (n = 68): 302.34 (296.31–308.37), probiotic (n = 77): 302.06 (296.31–307.81) mIU/ml] (p = 0.996). Probiotics may enhance specific antibody responses in infants receiving certain Hepatitis B vaccine schedules.

Healthcare-associated infections, also referred to as ‘hospital-acquired’, ‘nosocomial’ or ‘hospital-onset’ infections, are defined as infections not present and without evidence of incubation at the time of admission to a healthcare set- ting.1 Infections occurring more than 48 h after admis- sion are usually considered to be healthcare-associated infections.2 One of the most common types is healthcare- associated diarrhoea (HAD). In children, rotavirus remains a leading cause of nosocomial gastroenteritis.3 One study showed that nosocomial rotavirus infection may occur in 27% of hospitalised children.4 However, the true burden may be underreported due to difficulties in gathering reliable data.2 HAD results in prolonged hospital stays and increased additional medical costs.5 The single most inexpensive procedure to prevent HAD is improved hand washing combined with isolation of infected children, although the effectiveness of these measures is unsatisfactory.

In children, nosocomial infectious diarrhea is commonly caused by enteric viral pathogens, especially rotavirus.1,2 Depending on population, type of hospital, and standard of care, the reported incidence rate ranges from 4.53 to 22.64 episodes per 100 admissions. Infants and toddlers are at the highest risk of acquiring nosocomial viral gastroenteritis.3 On the other hand, enteric bacteria are rarely responsible for sporadic episodes of nosocomial diarrhea in children (<1% of cultured cases),5 with Clostridium difficile being the most prevalent bacterial pathogen.6,7 A common noninfectious cause of nosocomial diarrhea is antibacterial therapy; the mechanism is presumably related to alterations of normal bowel microflora and colonization by resistant flora. Nosocomially acquired diarrhea can prolong hospital stay and increase medical costs.4 We have shown that 48.8% of episodes of rotavirus nosocomial gastroenteritis prolonged hospital stay by 5.9 days per episode on aver- age, resulting in a significant increase in total cost of hospital treatment.1 Thus there is a strong need for cost- effective measures to prevent hospital- acquired diarrhea. In 1994, Saavedra et al8 reported that probiotics may be effective in prevention of diarrhea in hospitalized children. In a double-blind, placebo- controlled trial, infants aged 5 to 24 months who were admitted to a long- term medical care hospital for treat- ment of non-gastrointestinal conditions were randomized to receive a standard infant formula or the same formula with Bifidobacterium bifidum and Streptococcus thermophilus. Over a 17-month period, 31% of the patients receiving the control formula, but only 7% of those receiving the supplemented formula, developed diarrhea; and 39% of the subjects who received the control formula and only 10% of those who received the supplemented formula shed rotavirus at some time during their hospitalization.

Functional gastrointestinal disorders (FGIDs) are de- fined as a variable combination of chronic or recurrent gastrointestinal symptoms not explained by structural or biochemical abnormalities.1 Since FGIDs in childhood are age dependent, the Rome Foundation established 2 different pediatric committees to identify the criteria for FGID diagnosis: the Infant/Toddler Committee (age up to 4 years)2 and the Child/Adolescent Com- mittee (aged 4-18 years).3 Infantile colic, gastroesophageal reflux, and constipation are the most common FGIDs that lead to referral to a pedia- trician during the first 6 months of life and are often respon- sible for hospitalization, feeding changes, use of drugs, paren- tal anxiety, and loss of parental working days with relevant social consequences.4 Although FGIDs have been considered self-limited pro- cesses, a low-grade mucosal inflammation and immune or mo- tor alteration has been found in infants affected by colic, re- gurgitation, and constipation. This early traumatic insult to the intestine may represent a risk factor for the development of irritable bowel syndrome and psychologic problems later in life.5-7 Recent work indicates a crucial role of the intestinal mi- crobiota in the pathogenesis of gastrointestinal disorders as in FGIDs,8 and many studies target probiotic therapy for spe- cific conditions such as colic,9 regurgitation,10 and constipation.11 The effect of a probiotic could play a crucial role in the modulation of intestinal inflammation. We performed a prospective, multicenter, double- masked, placebo-controlled randomized clinical trial to evalu- ate whether oral supplementation with Lactobacillus reuteri DSM 17938 during the first 3 months of life can reduce the on- set of colic, gastroesophageal reflux, and constipation in term newborns and thereby reduce the socioeconomic impact of these conditions.

The nature and role of human milk microbiota in the early colonization and protection of infants from infection is the subject of increasing research. This study investigated the occurrence of Lactobacillus reuteri in milk of nursing mothers living in rural or urban areas in different geographical locations. Breast milk samples were collected from 220 mothers, 6 32 days after delivery, and analysed for the presence of total lactobacilli and L. reuteri. In all, 50% of mothers from rural areas in Japan and Sweden were L. reuteri-positive, whereas mothers from urban areas in South Africa, Israel and Denmark had very low or non-detectable levels. Overall, 15% of mothers had detectable L. reuteri in their milk. There were no significant differences in the prevalence of total Lactobacillus or L. reuteri in women from rural and urban habitats in the participating countries.

Rapid weight gain in infancy is associated with an increased risk of later obesity in a large number of observational studies sum- marized in 3 recent systemic reviews (1–3). Compared with breastfed infants, formula-fed term infants have greater body weight gains in infancy (4–6). The greater weight gain in formula- fed infants than in infants fed breast milk might be explained by different metabolizable substrate intakes (7), particularly protein: protein intake per kilogram body weight is 55–80% higher in formula-fed than in breastfed infants (8). It was proposed that a higher protein intake stimulates secretion of insulin-like growth factor I (IGF-I) and consecutively cell proliferation, which leads to accelerated growth and increased adipose tissue (7, 9). A positive association of protein intake with early growth was seen in 2 observational studies (10, 11); whereas no effect on growth in the first months of life was seen in other studies (12–14). Some observational studies found a higher protein intake in the first 2 y of life that was predictive of overweight in later childhood, whereas energy, carbohydrate, or fat intake was not predictive (9, 10, 15–17).

It is known that the immune system of newborns is T helper (Th) 2 biased during pregnancy. After birth, maturation of the immune system is age-dependent, and the development of the Th1 immune response can reset the Th1/Th2 balance. Exposure to environmental microbial components is suggested to play an important role in the maturation process. Probiotics are live microorganisms that, when administered orally in adequate amounts, confer a beneficial effect on the host.[7] Modulation of the infant gut microbiota with probiotics has been proposed as a potential approach for the treatment and prevention of immune-mediated diseases. Recently, several cohort studies have investigated the immune modulative effects of probiotic supplementation on infants and pregnant women and observed that probiotics supplementation can reduce the risk for atopic diseases.