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August 21, 2023 

Section I

Literature Review

1) From Cell Host and Microbe - "The microbiomes of cesarean-born infants differ from vaginally delivered infants and are associated with increased disease risks.

Vaginal microbiota transfer (VMT) to newborns may reverse C-section-related microbiome disturbances. Here, we evaluated the effect of VMT by exposing newborns to maternal vaginal fluids and assessing neurodevelopment, as well as the fecal microbiota and metabolome. Sixty-eight cesarean-delivered infants were randomly assigned a VMT or saline gauze intervention immediately after delivery in a triple-blind manner. Adverse events were not significantly different between the two groups. Infant neurodevelopment, as measured by the Ages and Stages Questionnaire (ASQ-3) score at 6 months, was significantly higher with VMT than saline. VMT significantly accelerated gut microbiota maturation and regulated levels of certain fecal metabolites and metabolic functions, including carbohydrate, energy, and amino acid metabolisms, within 42 days after birth. Overall, VMT is likely safe and may partially normalize neurodevelopment and the fecal microbiome in cesarean-delivered infants."(Zhou et al. 2023)

This remains a completely logical decision for me. Why not do what is naturally occurring every day. Anthropologic reality is that VMT occurred since the dawn of time by a vaginal delivery. To have a philosophical or medical issue with safe VMT is to have a problem with natural human history. Nonsense to me. We, as a medical society, can have carve out situations like herpes viral infections and active HIV while allowing the remainder of natural events to persist as expected.

2) Type 2 non-autoimmune diabetes following covid 19 is significantly elevated. National Health Service in the UK looked at millions of patients and found a signal of increased disease risk if a patient had significant natural disease, especially if hospitalized and unvaccinated. (Taylor et. al. 2023) To me this is a clear indication that the inflammatory state of Covid 19 lead to an acceleration of metabolic issues that were likely already on the disease trajectory.

3) More data in preparation for the upcoming podcasts with Dr. Peter Unger and Dr. Doug Thompson. "While the effects of dietary patterns on cardiovascular risk and diabetes have been well studied, the evidence is scarce as to which diet has the greatest anti-inflammatory potential and how dietary patterns are associated with periodontitis. In the Hamburg City Health Study (HCHS), we developed an anti-inflammatory dietary score using a data-driven approach based on the relationship of relevant selected food groups with inflammatory biomarkers (hsCRP and IL-6). The aim of this cross-sectional study was to evaluate the association between the anti-inflammatory dietary score and the incidence of periodontitis in Hamburg, Germany. A total of n = 5642 participants fit the required inclusion criteria and were selected for analysis. Periodontal disease was assessed using probing depth, gingival recession, and bleeding on probing. Dietary intake was measured using a food frequency questionnaire (FFQ). A self-developed anti-inflammatory dietary score served as the key explanatory variable. Higher scores reflected lower inflammatory processes (measured through the biomarkers hsCRP and IL-6). Several covariates were included in the regression analysis. Regressions revealed that a higher anti-inflammatory dietary score was significantly associated with lower odds to be affected by periodontal disease in an unadjusted model (OR 0.86, 95% CI 0.82–0.89, p < 0.001) and in an adjusted model (age, sex, smoking, diabetes, hypertension, and physical activity) (OR 0.93, 95% CI 0.89–0.98, p = 0.003). Our study demonstrated a significant inverse association between an anti-inflammatory dietary score and periodontitis. Individuals with higher intake of proinflammatory nutrition should be specifically addressed to avoid periodontitis."(Lieske et al. 2023)

This is an unsurprising result based on the mechanisms of inflammation that lead to periodontal disease. Refined carbohydrates are notorious inducers of microbial growth with acid producing bacteria that damage tooth enamel as well as periodontal tissue leading to systemic inflammation over a lifetime. Measuring inflammatory markers gives this study better weight to the results. Food frequency questionnaires are notoriously inaccurate leaving the data more functional with the added objective inflammation markers.

4) More on periodontal disease. In the journal Neuroinflammation we see a study analyzing the effects of periodontal disease, PD, and the associated bacteria with the risk of microglial activation and in specific inflammation induced disease. The authors write: "We showed that inducing PD in mice results in microglia activation in vivo and that PD-associated bacteria directly promote a pro-inflammatory and phagocytic phenotype in microglia. These results support a direct role of PD-associated pathogens in neuroinflammation." (Almarhoumi et. al. 2023) Remember that microglia are the resident immune macrophages in the brain and are responsible for much of the neurodegeneration seen in Alzheimers and other dementias. If PD is also affecting the brain via the microglia, then it behooves us all to start paying alot of attention to oral microbiomes and quality oral care.

For the immunology readers: " Cells were stimulated with different MOIs of K. variicola (1, 5, 10, 20, and 50). IL-1β, IL-6, and NF-kB mRNA expression were significantly and dose-dependently increased after stimulation with K. variicola . We also measured mRNA expression levels of TLR2, TLR4, and TLR9. While TLR4 expression did not show any difference after stimulation with K. variicola, TLR2 and TLR9 mRNA expression were significantly increased in microglial cells, suggesting that TLR2 and TLR9, but not TLR4, are the microglial cell receptors that bound to K. variicola upon stimulation in line with the impact of whole PD-associated microbiome shown above." (Almarhoumi et. al. 2023)

5) In a new study in the journal Cell, we see a newly identified fatty molecule in breast milk that has the ability to bind to stem cells that are in the brains of mice encouraging them to become myelin producing cells known as oligodendrocytes. In turn, these oligodendrocytes help to repair damaged neurons of premature infants. This is a first identification of a novel molecule with the potential to reverse neuronal damage related to prematurity. Human studies will be forthcoming. From the study: "White matter injuries (WMIs) are the leading cause of neurologic impairment in infants born premature. There are no treatment options available. The most common forms of WMIs in infants occur prior to the onset of normal myelination, making its pathophysiology distinctive, thus requiring a tailored approach to treatment. Neonates present a unique opportunity to repair WMIs due to a transient abundance of neural stem/progenitor cells (NSPCs) present in the germinal matrix with oligodendrogenic potential. We identified an endogenous oxysterol, 20-αHydroxycholesterol (20HC), in human maternal breast milk that induces oligodendrogenesis through a sonic hedgehog (shh), Gli-dependent mechanism. Following WMI in neonatal mice, injection of 20HC induced subventricular zone-derived oligodendrogenesis and improved myelination in the periventricular white matter, resulting in improved motor outcomes. Targeting the oligodendrogenic potential of postnatal NSPCs in neonates with WMIs may be further developed into a novel approach to mitigate this devastating complication of preterm birth."(Chao et. al. 2023)

6) Early childhood abuse and social deprivation in a mouse model leads to changes in steroid hormone activity that causes excessive synaptic pruning of certain neurons in the brain via astrocytes. (Byun et. al. 2023) These actions lead to increased mental health concerns. The actions of the astrocytes leads to decreased neuronal activity which explains the mental health issues. When the study team ablated the pathway leading to the astrocyte induced damage, the symptoms were prevented. More work to be done here as it relates to early childhood abuse and methods to reduce and reverse mental struggles.

That's it for today,

Dr. M

Zhou Cell Host and Microbe

Taylor MedRxIV

Lieske Nutrients

Almarhoumi J Neuroinflamm

Chao Cell Stem Cell

Byun Y. Cell Immunity