Low-Dose Antibiotics During Early Infancy Trigger Obesity Later in Life

Early life is a critical development period in many respects, and particularly as it relates to gut microbial composition. Even before birth, gut microbes are transferred from mother to fetus, a transfer that continues during birth and later via breast milk. Once established, gut microbes in the infant play a protective role on the infant’s health.

A disturbance of gut microbial balance during early development has been linked to obesity. Epidemiological studies have found that exposure to antibiotics during infancy can lead to weight gain later in life.1-3 Animal studies have confirmed this link and determined that low-dose antibiotics administered after weaning lead to an increased fat mass, altered metabolic hormones, liver metabolism, and microbiota composition.4

A recent study published in the journal Cell followed up this research and confirmed that the increased fat mass was the result of changes in gut bacteria and not to the antibiotic itself.5 Low-dose penicillin was administered either to the mother before birth and then to mouse pups until weaning, or they were administered to pups after weaning. In both cases, alterations in gut bacterial balance occurred, but they fully recovered after antibiotics were stopped. On the other hand, metabolic changes occurred that persisted into adulthood. Increased growth, which included lean mass, fat mass, bone mass, or a combination were induced by the antibiotic exposure. In addition, decreases were found in four main bacteria: Lactobacillus, Allobaculum, Rikenellaceae, and Candidatus arthromitus. Finally, a decrease in intestinal immune responses and impaired intestinal barrier function were found, which may help explain how bacteria might trigger metabolic dysfunction.

To confirm that these metabolic effects were the result of microbial alterations, the researchers transplanted feces from the obese mice into germ-free mice who inherited the altered gut microbes and went on to gain fat mass in a similar manner. They proposed the term microbe-induced obesity (MIO) as a condition of increased fat accumulation that results from alterations in gut bacteria. This study suggests that losses of the four bacteria are detrimental when they occur (Lactobacillus, Allobaculum, Rikenellaceae, and Candidatus) during the critical developmental period of early infancy.

“These four organisms have either metabolic and/or immunologic interactions, which may contribute to the observed protection from weight gain in the control animals,” noted the researchers.

“This highlights a need for judicious use of antibiotics in clinical practice in early life,” noted Martin Blaser, MD, lead researcher and author of the eye-opening book Missing Microbes. Brenda and I discuss some of his research in our new book, The Skinny Gut Diet.

Microbe-induced obesity in conjunction with diet-induced obesity (because the two go hand in hand as we discuss in our book) are a sure set up for difficult-to-lose weight gain. This was confirmed by feeding a high-fat diet to the mice given low-dose penicillin, in which they found an amplified increase in fat mass. The researchers suggest that restoration of lost microbes after antibiotic use during infancy as a potential strategy to reverse MIO and its related effects.

It is clear to me that pre- and probiotics during pregnancy will prove to be a major way to ensure that the immune system and intestinal lining of the fetus will optimally develop, which may negate the need for antibiotics, for the most part. In the event that there is a need for antibiotics, I think it will soon become standard of care to place everyone who is taking antibiotics on probiotics to maintain microbiome stability. Probiotics can provide high colony count numbers with increased species of commensal bacteria to block the emergence and dominance of pathogenic bacteria that can spell disaster.

Further studies are needed to confirm these effects in humans, and to determine what species are key to the prevention of weight gain in later life.

References

  1. Ajslev TA, Andersen CS, Gamborg M, et al., “Childhood overweight after establishment of the gut microbiota: the role of delivery mode, pre-pregnancy weight and early administration of antibiotics.” Int J Obes (Lond). 2011 Apr;35(4):522–9.
  2. Murphy R, Stewart AW, Braithwaite I, et al., “Antibiotic treatment during infancy and increased body mass index in boys: an international cross-sectional study.” Int J Obes (Lond). 2014 Aug;38(8):1115–9.
  3. Trasande L, Blustein J, Liu M, et al., “Infant antibiotic exposures and early-life body mass.” Int J Obes (Lond). Jan 2013; 37(1): 16–23.
  4. Cho I, Yamanishi S, Cox L, et al., “Antibiotics in early life alter the murine colonic microbiome and adiposity.” Nature. 2012 Aug 30;488(7413):621–6.
  5. Cox LM, Yamanishi S, Sohn J, et al., “Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences.” Cell. 2014 Aug 14;158(4):705–21.