Misuse of antibiotics in childhood may increase obesity and overweight

Every child is a little angel to his or her parents and the source of joy for the whole family. The health of children is always the top priority of a family. It is a good thing for children to eat more and grow stronger, but being overweight or obese is not good and is also a disease, which must be taken seriously.

According to the "Report on the Nutrition and Chronic Disease Status of Chinese Residents (2020)" released by the National Health Commission, the overweight and obesity rates of children and adolescents aged 6-17 in my country are 11.1% and 7.9% respectively, which together account for nearly one-fifth. The overweight and obesity rates of children under 6 years old are 6.8% and 3.6% respectively, which together account for one-tenth.

Obesity has already had a great negative impact on the health of adults, not to mention growing children. Obese children often suffer from joint, bone, and muscle damage, and their motor skills and physical fitness are significantly lower than those of children of normal weight. Obesity can even affect intellectual development, causing obese children to have significantly lower intelligence levels than children of normal weight. There are also many metabolic diseases that should not appear at their age. It is not uncommon for children to be diagnosed with fatty liver, diabetes, high blood lipids and other diseases. Obese children are also prone to psychological problems, such as excessive inferiority and loneliness.

Figure 1. Trends in the prevalence of overweight and obesity among children and adolescents aged 7 to 18 years in my country from 1985 to 2010 (male) [1].

Childhood obesity is caused by both genetic and environmental factors. High-sugar and high-fat diets and lack of exercise are well-known environmental factors that cause childhood overweight. In recent years, scientific research has brought to light a new environmental factor: antibiotics . Epidemiological studies have found that children who use antibiotics too early or repeatedly in childhood are more likely to suffer from obesity[2]. A recent scientific study has revealed the reasons behind this, showing that the abuse of antibiotics such as penicillin can destroy a type of beneficial symbiotic bacteria belonging to the genus Lactobacillus in the small intestine, affecting the absorption and metabolism of fat in the intestine[3].

But isn’t lactic acid bacteria a type of bacteria? How can it affect the absorption of our digestive system? In fact, some bacteria can directly help us break down large molecules of cellulose or fat, and some bacteria can change the metabolism and absorption of intestinal cells by secreting some unique substances. The symbiotic bacteria of the genus Lactobacillus affect fat metabolism through the second pathway. Some lactobacilli can synthesize a bacterial metabolite called phenyllactic acid , which can promote the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) in intestinal epithelial cells. This key receptor is involved in the decomposition, synthesis, and transportation of various metabolites such as fatty acids, cholesterol, glucose, and amino acids in the intestine, including reducing the absorption of triglycerides and their accumulation in the blood. The triglyceride level in the blood is one of the indicators of obesity. Excessive triglycerides can lead to hypertriglyceridemia and other cardiovascular diseases [3]. Therefore, ensuring the normal function of this receptor can make us less likely to gain weight.

However, when antibiotics are combined with a high-fat diet, a large number of lactobacilli are killed, the synthesis of phenyllactic acid is greatly reduced, and the activity of small intestinal epithelial cells is also disrupted. Not only is the expression of PPAR-γ impaired, but the expression of approximately 200 genes involved in lipid digestion and absorption is affected to varying degrees, and obesity and metabolic dysfunction are the consequences.

Figure 2. Antibiotics destroy intestinal flora, leading to disorders in fat metabolism and absorption [4].

So why is childhood obesity more susceptible to antibiotics? In fact, everyone is almost sterile when they first come into this world. Through contact with the outside world, bacteria gradually appear on our skin and in our intestines. The types of intestinal microbiota in our early life are very limited. As the baby grows, especially after weaning and starts to eat a variety of foods, the complexity and richness of the intestinal flora rise sharply. 1-3 years old is the critical period for the maturation of intestinal flora, which is very sensitive to the composition of the diet and the use of antibiotics. At this time, frequent use of antibiotics is more likely to cause intestinal flora disorders, and such "bad" flora will even accompany us for a long time. Children aged 3-5 have formed flora similar to those of adults, and the composition tends to be stable. At this time, the intestinal flora is more tolerant to interference from external factors, but frequent use of antibiotics will still cause considerable damage and lead to flora imbalance.

It is worth mentioning that the experimenters also found that additional supplementation of Lactobacillus or phenyllactic acid after using antibiotics can effectively slow down weight gain and improve the symptoms of obesity. There is hope to launch clinical trials and develop new drugs for the treatment of childhood obesity.

Of course, the use of antibiotics not only affects the content of lactobacilli, but also destroys the growth of other intestinal symbiotic bacteria. The normal metabolism of lipids and proteins is the result of the coordinated cooperation of the bacterial flora. The role of other symbiotic bacteria in the metabolic process and their relationship with the use of antibiotics are the next key research topics for scientists.

Although this study was done in a mouse obesity model, many of the changes in gene expression are consistent with obese patients. It not only shows how the microbiota communicates with intestinal epithelial cells in early life, providing new evidence for the relationship between early antibiotic exposure and childhood obesity, but also provides new ideas for the treatment and prevention of childhood obesity and overweight.

References
1. Zhu Yimin, Zhou Dan. Epidemiological characteristics and changing trends of obesity in children and adolescents[J]. Chinese Journal of Practical Pediatrics, 2014, 29 (8): 563-567. DOI: 10.3760/cma.j.issn.2095-428X.2014.08.002

2.Ajslev TA, Andersen CS, Gamborg M, Sørensen TI, Jess T. 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;35:522–9. doi: 10.1038/ijo.2011.27.

3.Duszka, K.; Oresic, M.; Le May, C.; König, J.; Wahli, W. PPARγ Modulates Long Chain Fatty Acid Processing in the Intestinal Epithelium. Int. J. Mol. Sci.2017,18,2559. https://doi.org/10.3390/ijms18122559

4.Catherine D. Shelton, Elizabeth Sing, Jessica Mo, et. al., An early-life microbiota metabolite protects against obesity by regulating intestinal lipid metabolism, Cell Host & Microbe, 2023.

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