Lipopolysaccharides
LPS for short, found on the outer membrane of gram-negative microbes, consists of three parts: Lipid A, an inner core oligosaccharide, and an outer core polysaccharide O-antigen. They are generally classified as endotoxins, activating the production of pro-inflammatory cytokines when they bind to certain receptors (i.e. TLR4, CD14, MD2) of the host. Through natural cell growth and cell death, LPS are synthesized and released into the environment, where cell death releasing greater amounts of LPS.
The inflammation caused by LPS can disrupt iron homeostasis. The immune system is known to respond by releasing iron-importing expressions that increase intercellular iron. This causes a temporary decrease in iron serum levels. This has the added effect of limiting the amount of iron that is available for pathogens. 1
Inhibition
Some gram-negative bacteria can produce LPS that can act as antagonists to the LPS produced by other gram-negative bacteria. This can be done by binding to the receptors of the host before any other LPS can bind to them. These tend to have a weaker effect on the host’s immune system and are less likely to induce an immune response. Other gram-negative bacteria, like E. coli, produce stronger forms of LPS which are typically the ones to induce many kinds of immune responses. 2 3
Lactoferrin
Iron is a necessary nutrient in the production of LPS by many gram-negative bacteria. Apolactoferrin can bind to iron, preventing many microbes from utilizing iron, including gram-negative bacteria,4 without preventing the body from absorbing iron when taken with iron.5 Lactoferrin can also bind to some of the same receptors that LPS binds to (e.g. CD14), acting as a LPS chelator. Supplementing with lactoferrin could lead to a positive adjustment in microbiome ratios. Breast milk, especially after having given birth, contains significant levels of lactoferrin. This adds to the importance of breastfeeding and why it should be done for long periods of time (i.e. at least a year).
Fruits
Some fruits contain proanthocyanidins (PACs) that bind to LPS, inhibiting the ability of LPS to bind to host receptors. Grape seed and cranberry extracts are rich in PACs that are known to bind and neutralize the LPS produced by gram-negative bacteria. Since the membrane of gram-negative bacteria are made up of LPS, these PACs can disrupt the structure and functions of some gram-negative bacteria, preventing them from utilizing the iron necessary for producing LPS. It should be noted that their effectiveness is dependent on gut microbiome composition.6 Conversely, these same PACs can increase the relative abundance of Bacteroidetes, which consist mostly of gram-negative bacteria.
Protection
The endotoxemia caused by LPS has been found to significantly reduce vitamin C serum levels.7 8 Increasing consumption of vitamin C helps to alleviate endotoxemia.8 Many fruits, especially berries, contain anthocyanins and polyphenols that assist in protecting the body from the negative effects of LPS. The poor bioavailability of polyphenols means that they would travel as far as the colon,9 potentially inhibiting the growth of opportunistic bacteria along the way.