Will Probiotic Supplementation For Newborns Protect Them From Asthma?
Researchers at UCSF have launched a study to evaluate whether active probiotic supplements can delay or prevent asthma in young children. The rationale for the intervention is grounded in the hygiene hypothesis. The suggestion is that our prevailing standards of hygiene lead to a lack of contact with bacteria in early life. Similarly, the hypothesis suggests that children have less exposure to viruses. The reduced opportunities for challenge compromises the robust development of an immune system that is protective against the development of asthma and other allergic diseases. Children who are born to parents who have asthma are thought to be particularly at risk.
It is axiomatic that clean water and high standards of food hygiene protect children. Nobody would suggest that children should be exposed to harmful microbes.
As Dr. Wiess, Professor of Medicine at Harvard Medical School, wryly remarked in an editorial for the New England Journal of Medicine:
The researchers have selected probiotics that are found in a wide range of foods such as yoghurt. Probiotics are live micro-organisms that are consumed in sufficient quantities to confer beneficial health effects. Probiotics are intended to encourage the colonisation of beneficial bacteria that inhabit the gastrointestinal system.
Eating dirt or moving to a farm are at best theoretical rather than practical clinical recommendations for the prevention of asthma...However, a number of environmental factors are known to be associated with a lower incidence of allergic disease early in life...The challenge will be … to determine the extent of exposure that will ensure safety and have the desired outcome—the development of a healthy child with a very low risk of autoimmune disease.
Researchers have successfully isolated several strains of Lactobacilli in human breast milk. Further analysis indicates that these Lactobacilli may offer anti-infective protection in Neonates.
The UCSF researchers have selected to investigate whether the administration of Lactobacillus GG supplements 'stimulates' the immune system: the study is Trial of Infant Probiotic Supplementation to Prevent Asthma, (TIPS). The study will involve 280 healthy full-term babies with either a mother or a father with asthma. For the first six months of life, half of the babies will receive a once-daily dose of active Lactobacilli GG and the other half will receive a placebo.
The babies will be monitored for three years with 6 follow-up visits. Researchers will collate and evaluate the data to see if supplementation prevents or delays the the early onset of asthma.
Earlier this year, researchers in Finland published a study about probiotic intervention in neonates. The babies received either the probiotic or a placebo for 6 months from birth. The researchers monitored the faeces of infants at 6 and 12 months to assess whether the Lactobacilli were present. They reported that although they did not find permanent establishment of the bacterium, they did find transient colonisation at 6 months of age. However,
the presence of the strain at the end of the administration period was correlated with a reduced prevalence of atopic eczema later in life.The TIPS study is still recruiting women who are pregnant and have a history of asthma or a partner with asthma to participate in the study.
It is annoying that TIPS has a website but does not give details of what they shall be monitoring in the infants. They do say they will monitor the children for early signs of asthma.
Some of the early signs include: frequent wheezing, wheezing without a cold or the flu, frequent “runny” nose, and eczema. There are also immune system signs that are sometimes associated with asthma.I'd have liked to see some detail about whether the TIPS researchers will investigate whether Lactobacillus GG colonises the guts of the infants. And whether this presence/colonisation is positively linked to a reduced prevalence of asthma symptoms at the age of 3. It is possible that some of the infants will be responders or non-responders to the supplementation. It is possible that the babies will have different levels of Lactobacilli depending on whether or not they were exclusively breast-fed, and for how long. Similarly, there may be different levels in babies who received colostrum which can help to establish friendly flora in the neonate digestive tract. So, there will be a number of sub-groups within this small study that will add to the difficulty of interpreting the results with confidence.
It would be useful if the researchers had stated how they will monitor the children for asthma. Although many children are being treated for asthma, and in accordance with their symptoms, it is not practical to confirm a diagnosis of asthma in young children. Diagnosis depends on spirometry, and that is not practical for use with the under-6s. The FDA has approved a new test for asthma that is suitable for children as young as two but this test is not widely available.
A previous study of the effect of long-term conumption of probiotic milk on infections in children attending day-care yielded modest results.
Lactobacillus GG may reduce respiratory infections and their severity among children in day care. The effects of the probiotic Lactobacillus GG were modest but consistently in the same direction.Nonetheless, Lactobacillus GG supplementation for Neonates is an attractive intervention that is probably cheap and easy to administer. TIPS may also be another way of studying the vexed question of whether exposure to antibiotics in early life is linked to childhood asthma.
FACT (Focus on Alternative and Complementary Therapies) recently published: Probiotics: targeting the paediatric population to reduce antibiotic consumption and resistance (not available online). There is widespread concern about the public health problem that is posed by antibiotic resistance but there is little evidence that probiotics are effective as primary therapies for disorders or as adjunctive treatments (e.g., to re-colonise the GI tract during the use of antibiotics).
The NASPGHAN Nutrition Report Committee recently published an overview of the use of probiotics in paediatric health care. The authors offered
a review and evaluation of the evidence or lack thereof to support a beneficial effect of probiotic agents in a variety of pediatric conditions and to review the safety and potential adverse events that may be encountered when using probiotics.The Committee emphasised that although probiotics are widely available in many countries, they are:
highly heterogeneous with differences in composition, biological activity, and dose among the different probiotic preparations.The Committee also noted that for some specific conditions, probiotics may contribute to clinical deterioration. It is important to note that the researchers are implictly using a certified active source of Lactobacillus GG with standardised doses. This experiment can not be tried at home. There is no clear understanding of the mechanisms by which probiotics may modulate various physiological functions. There are no accepted therapeutic doses, no specific recommendations of strains for particular therapeutic actions, no approved guidelines for frequency, or the duration of treatment for different probiotic strains.
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