This post covers a Chinese study testing the hypothesis that the so called “Western Style Diet” for 9 weeks could influence they way mice respond to 2,4,6 trinitrobenzene sulfonic acid to induce colitis. Trinitrobenzene sulfonic acid has a very interesting reaction scheme illustrated in the featured image. The authors were doing three things: (1) creating protein adducts, (2) releasing sulfate, and introducing a ligand for a transcription factor as will be discussed.
Lin L, Li Y, Zhou G, Wang Y, Li L, Han J, Chen M, He Y, Zhang S. Multi-Omics Analysis of Western-style Diet Increased Susceptibility to Experimental Colitis in Mice. J Inflamm Res. 2022 Apr 21;15:2523-2537. PMC free article
Supplementary Table 1 Ingredients of Mice Chow
These authors fed experimental mice a WSD and a control diet from weaning. After 9 weeks, the mice were treated with 2,4,6 trinitrobenzene sulfonic (TNBS) acid to induce colitis, and the control group was treated with 50% ethanol (commonly used IBD animal model).
The big difference seems to be in carbs from corn starch versus sucrose. The HFHC-C7 appears to be a more adult version of the AIN93G starter diet. From a human diet perspective, whole grain corn would have been more healthy. The Western diet seems to have fat calories coming from milk fat as opposed to vegetable oils. Neither die seems to contain any indigestible carbohydrate to support microbiome growth. Maltodextrin is digestible and can cause spikes in blood glucose and maybe even alter the microbiome in negative ways according to Medical News. It should be noted that the WSD did it’s job by damaging the livers of the mice.
|Mineral Mix #200000||0||35||0||0||35||0||0||0||0|
|Mineral Mix #210025||0||0||0||0||0||0||0||35||0|
|Vitamin Mix #300050||4||10||40||4||10||40||0||0||0|
The analytical techniques
Genome-wide microarray and liquid chromatography-tandem mass spectrometry were used to identify the differential transcripts and metabolites of experimental colitis with and without pre-illness WSD. This is how the two diets compared
TNBS binds to the acryl hydrocarbon receptor (AhR). AhR binds to the acryl hydrocarbon response element and induces the transcription of genes for cytochrome P450s that make all sorts of modifications to xenobiotics.
Brief recap of histology and gross biology
- Western diet made TNBS induced colonic shortening and histopathological score slightly worse
- In control animals , not treated with TNBS, the length of colon and weight gain over time were the same. The hepatic score was worse in the Western diet mice
Supplementary Table 5 Differentially Expressed Gene KEGG Pathways between the WSD-TNBS Group and the AIN93G-HFHCC7-TNBS Group. In retrospect, maybe I should have left in the xenobiotic metabolizing pathway stuff. The ones involving what we’ve been talking about are highlighted. Do changes in tryptophan metabolism and serotonin neurons change colonic transit time in Western vs control diet in mice treated with TNBS?
|Pathway ID||Pathway||Number of Involved Genes||Upregulation/Downregulation||P Value|
|mmu04261||Adrenergic signaling in cardiomyocytes||23||Up||9.8E-04|
|mmu00512||Mucin type O-glycan biosynthesis||6||Up||1.9E-02|
|mmu04071||Sphingolipid signaling pathway||16||Up||2.8E-02|
|mmu04921||Oxytocin signaling pathway||19||Up||2.9E-02|
|mmu04020||Calcium signaling pathway||22||Up||2.9E-02|
|mmu04080||Neuroactive ligand-receptor interaction||38||Down||3.8E-03|
I really don’t put much stock in the diet as really being “Western.” The metabolites and hormones they detected by electrospray ionization mass spectrometry are interesting. They saw a lot of modifications of short chain fatty acids too.
Supplementary Table 6 Metabolites Differentially Expressed in the Colonic Tissue between the WSD-TNBS Group and the AIN93G-HFHCC7-TNBS Group
|Uridine monophosphate (UMP)||C9H13N2O9P||16.00|
|Riboflavin (Vitamin B2)||C17H20N4O6||0.47|
|7Z, 10Z, 13Z, 16Z, 19Z-Docosapentaenoic acid||C22H34O2||0.24|
Supplementary Table 8
Pearson correlation analysis of differential genes and metabolites in the comparison of the WSD-TNBS group and AIN93G-HFHCC7-TNBS group. Whether the reader agrees with the authors on their definition of normal control diets and a Western diet, these results are very interesting. The main driver of differences seems to be cytochrom P450s Cyp11b1 and Cypa1a. Srd5a3 is a steroid reductase. Hsd17b6 is involved in androgen metabolism. A negative Pearson correlation coefficient indicates an inverse relationship. These results strongly suggest that the mRNA that they are measuring are being translated into enzymes that are active.
|Gene||Metabolite||Pearson correlation coefficient||P value|
|Differential genes and metabolites in colonic tissue|
Supplemental data table
Notes: The red square represented differential genes, the green circle represented differential metabolites, the solid edge meant the Pearson Correlation Coefficient (PCC) >0.8, and the dotted line meant the PCC <−0.8. We were all intovaleric acid. Having Cyp2p20 or something increases 5-adetamido valerate… valerate with an imino group on the carboxyl group. Some other Cyp is putting a hydroxyl group on the 3rd carbon of butyrate… All of this in the blood plasma.
Conclusions and followup questions ?
These authors showed some pretty interesting interaction between two diets, neither of which would be optimal for humans, and a toxin that does at least three things. The results do raise followup questions:
- What if the control rats were fed a diet considered healthy for humans with “prebiotic” carbohydrates?
- What if the treatment group was given an inorganic sulfur compound like sulfate or sulfite?
- What changes could be happening to the microbiome?