Update PROTECT.

_posts/2025-02-23-PROTECT.md

@@ -20,13 +20,41 @@ though to be primary suspects in these case.
 To get an early snapshot of the scene, we examined pediatric UC patients, aged
 4-17. These subjects have not undergone treatment, promising a less obstructed
 window into onset of inflammation. Through investigation of paired stool and
-plasma, we got a window into bacterial communities and their chemical
+blood, we got a window into bacterial communities and their chemical
 repertoire that characterizes ulcerative colitis at its earliest stages.
 
+Various different practives for exploring microbial compositions exist.  We
+opted for <i>de novo assembly</i>, which attempts to take bits and pieces of
+microbial DNA and automatically reconstruct bacterial genomes, even if most
+these microbes have previously been unknown and can even reveal bacterial
+viruses (phages).  As opposed to using known bacterial genome catalogs, this
+approach makes it harder to compare bacterial strains between studies, but on
+the plus side enables us to utilize most of the collected material.
 
+Patients with most severe inflammation harboured bacteria with special
+metabolic tricks up their collective sleeves. 
+
+Most prominent of those was
+Veillonella parvula, which typically resides in the oral cavity but tends to
+relocate to the gut when inflammatory conditions favor its colonization.
+
+
+
+
+
+Disease progression 
+
+The analysis reveled a
+
+
+Delving into microbial compositions can be done in many ways. Here, we opted 
+
+Delving into bacterial compositions
 
 
 Veillonella
+Reference-free metagenomic assemblies and analysis of primary metabolism pathways revealed an enrichment of nitrate-utilizing operon present in characteristic Gram negative bacteria: E. coli, Klebsiella pneumoniae and Veillonella parvula. The latter is an abundant representative of oral microbiota, whose nitrate- and lactate-utilizing capabilities were characterized previously in our lab (PMID 36138166). Veillonella primary metabolism thus makes it very amenable to survival in the inflamed gut, characterized by increased host-derived nitrate (PMID 23393266), likely hypoxia (PMID 21323543) and increase of lactate due to preference for fermentation over aerobic respiration. Indeed, Vellonella thrive in presence of lactic acid bacteria or in exercise-elevated lactate environments (PMID 31235964). In addition, Veillonella showed a significant overabundance in patients that required collectomy (PMID 38215740).
+
 
 
 Dipeptides, bits and pieces of proteins, which are suspected to be a result of
@@ -124,6 +152,17 @@ Lipids, endocannabinoid receptors.
 
 
 
+Hypoxia induces inflammation; high altitude climbers experience hypoxia an increase in proinflammatory cytokines like IL6.
+
+Conversely, inflammation can induce hypoxia. Intestinal cells are anaerobic and oxycen increases steeply towards the lumen. 
+Inflammation increases metabolic demand for O2; pathogens can mop up oxygen, resulting in hypoxia, which snowballs in even more inflammation. 
+This is seen as an increase in HIF1a, HIF2a hypoxia inducible factors. Hypoxia upregulates oxygen-dependent gene expression programs.
+
+Cells begin to ferment, producing lactate.
+
+
+
+