How might microorganisms move from one part of the body to another? Let’s begin with the womb, where the concept of fetal colonization has rapidly gained acceptance, indicated by meconium and placental microbe studies.
A new stool study reveals virus populations are dynamic in healthy infants. The infant virome is most diverse early in life, then bacteria flourish as viral counts decline. Most interestingly, the main types of viruses were identified as bacteriophages.
These viruses infecting bacteria were found richest and most diverse in early life. Bacteriophages may preferentially infect gram-negative lipopolysaccharide-producing bacteria, but also gram-positive microbes with peptidoglycan cell walls. In the small intestine, fats form into balls called chylomicrons composed mainly of triglycerides. Chylomicrons bind with toxic lipopolysaccharides (LPS) via lipopolysaccharide-binding protein (LBP) as well as lipoteichoic acid (LTA) from gram-positive bacteria such as Staphylococcus. Chylomicrons then enter general circulation via lymphatics of the small intestine known as Peyer’s patches, lacteal or lymphatic ducts. Chylomicrons deliver LPS-producers along with their bacteriophages to the placenta where they may colonize the growing fetus. Amniotic fluid flora accounts for a greater abundance of flora in meconium when compared to vaginal and oral flora. Thus, bacteriophages may arrive in the womb via bacterial hosts, and vertical transmission of maternal gut bacteria to the fetus may be achieved in the placenta through lipids. This may be an important example of microorganisms moving through body “barriers”.
How do translocated maternal gut microbes affect fetal gut-brain development? Gut microbiota modulate mammalian early brain development, so the colonized fetal gut may be a major contributor to fetal brain development. LPS-producing Proteobacteria and Staphylococcus are associated with preterm birth and are perhaps a cause of placental folds linked with autism. Assembly of gut bacteria is based on gestational age where Bacilli such as Staphylococcus are the first to flourish, then Proteobacteria followed by Clostridia, so preterm infants would naturally have relatively high levels of Bacilli and Proteobacteria beginning in the womb.
LBP and LPS are studied related to Parkinson’s, schizophrenia, and amyloids in Alzheimer’s. LPS increases permeability of the blood-brain barrier, associated with leptin resistance, dysregulating histamine receptors leading to the hypothalamic inflammation also known in obesity. Interestingly, elevated triglyceride levels were found to precede amyloid deposition in Alzheimer’s. And bacterial amyloids were found to produce the same immune response as Alzheimer’s amyloids. What is generally not factored into LPS studies is possibility of microbial translocation, since LPS is part of the cell wall of gram-negative bacteria. Given intestinal gram-negative bacterial overgrowth, chylomicron LBP inactivation of LPS may be less efficient. LPS-producing bacteria riding chylomicrons out of the small intestine may also explain triglyceride levels associated with heart disease in cases where atherosclerosis begins with infection. Leaky gut is not required for these bacteria to end up elsewhere in the body, as microbes and their toxins also reach the liver via the portal vein, which provides 80% of the liver’s blood flow. Also, Bacilli and Proteobacteria are found in the blood and tissue of type 2 diabetics, translocated from the intestines and associated with a high-fat diet. And intestines are not the only source of fat: chylomicron uptake in bones suggests a gut-bone-brain axis.
Evidence to date is compatible with the hypothesis that fetal gut microbes are of maternal intestinal origin via chylomicrons. Apparently, there are no privileged sites of the body, including the brain. This realization of microbial translocation as a natural process hopefully inspires wise environmental, dietary, and medical choices that support a healthy microbial balance, especially in the small intestine where translocation appears to begin, affecting all organs.
Lim ES, et al. (2015) Early life dynamics of the human gut virome and bacterial microbiome in infants. Nature Medicine doi:10.1038/nm.3950 Elmore BO, et al. (2015) Apolipoprotein B48, the structural component of chylomicrons, is sufficient to antagonize Staphylococcus aureus quorum-sensing. PLOS ONE DOI: 10.1371/journal.pone.0125027 Rebholz SL, et al. (2011) Dietary fat impacts fetal growth and metabolism: uptake of chylomicron remnant core lipids by the placenta. American Journal of Physiology – Endocrinology and Metabolism DOI: 10.1152/ajpendo.00619.2010 Vors C, et al. (2015) Postprandial endotoxemia linked with chylomicrons and lipopolysaccharides handling in obese versus lean men: A lipid dose-effect trial. Journal of Clinical Endocrinology & Metaoblism DOI: http://dx.doi.org/10.1210/jc.2015-2518
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