Effect of Food Endotoxin on Infant Health

Abstract

Endotoxin is a complex molecule derived from the outer membrane of Gram-negative bacteria, and it has strong thermal stability. The processing of infant food can kill pathogenic bacteria but cannot remove endotoxin. Because the intestinal structure of infants is not fully developed, residual endotoxin poses a threat to their health by damaging the intestinal flora and inducing intestinal inflammation, obesity, and sepsis, among others. This paper discusses the sources and contents of endotoxin in infant food and methods for preventing endotoxin from harming infants. However, there is no clear evidence that endotoxin levels in infant food cause significant immune symptoms or even diseases in infants. However, in order to improve the safety level of infant food and reduce the endotoxin content, this issue should not be ignored. The purpose of this review is to provide a theoretical basis for manufacturers and consumers to understand the possible harm of endotoxin content in infant formula milk powder and to explore how to reduce its level in infant formula milk powder. Generally, producers should focus on cleaning the milk source, securing the cold chain, avoiding long-distance transportation, and shortening the storage time of raw milk to reduce the level of bacteria and endotoxin. After production and processing, the endotoxin content should be measured as an important index to test the quality of infant formula milk powder so as to provide high-quality infant products for the healthy growth of newborns.

Endotoxin Content in Neonatal Formulas, Fortification, and Lactoferrin Products: Effect on outcomes and need for measurement in enteral products and guidance on acceptable limits.

“…There is some evidence that low amounts of endotoxin may be bene cial for both the host and its microbiome. (Wu et al, 2021) Animal studies have shown that low endotoxin amounts may have a probiotic effect, reduce allergic diseases, and aid immune development. (Inagawa et al, 2011;Smit et al, 2009;Taniguchi et al, 2009;Wassenaar and Zimmermann, 2018) Further study of this area is needed as safe amounts of endotoxin may depend on gut health and host immunity.…”

“…Several factors in the collection, management and production of milk and milk-derived products can affect endotoxin content. (Wu et al, 2021) While pasteurization eliminates bacteria, if there are large amounts of Gram-negative bacteria present at the time of pasteurization, high amounts of endotoxin will be released into the milk. After milk collection, milk can be stored in milk tanks and then transported at temperatures in which some Gram-negative bacteria (e.g.…”

“…While enteral endotoxin or lipopolysaccharide (LPS) can be associated with bowel injury that may lead to microbial gut translocation and necrotizing enterocolitis (NEC), low levels may be non-toxic and are present from the microbiome and in enteral products administered to neonates. (Hsueh et al, 2003;Wu et al, 2021) The United States Food and Drug Administration (FDA) has given guidance for an intravenous endotoxin dose threshold of 5 EU (endotoxin unit)/kg/hour which would be 120 EU/kg/day, but there is no guidance for enteral intake of endotoxin for enteral nutrition or medications.…”

“…Townsend et al examined endotoxin content in 31 powdered infant formulas and found 40 to 55,000 EU per gram with an estimated daily exposure ranging from 67 to 97,670 EU/kg. (Townsend et al, 2007;Wu et al, 2021) Recently, another study found endotoxin content in infant formulas ranged between 6 EU/ml to 9080 EU/ml for 149 reconstituted samples with an estimated daily exposure (based on 150 ml/kg/d enteral intake) ranging from 900 to 1,362,000 EU/kg. (Wu et al, 2022) Comparatively, animal models of NEC that utilize endotoxin require a minimum of 1,000,000 EU/kg in addition to other stressors such as hypoxia and hypothermia.…”

“…(Ren et al, 2019) (Hsueh et al, 2003;Zhang et al, 2020) While a healthy infant gut, mature immune system and intestinal barrier can contain certain amounts of endotoxin, preterm and sick newborns or its with gut disease may not be able to contain the same amounts. (Wu et al, 2021) While these studies established that endotoxin is present and the varying amounts that are contained in infant formulas, they did not examine preterm infant formulas where certain endotoxin amounts potentially could cause harm compared to formulas given to older infants during the rst year after birth.…”