gut health

Western Diet and Colitis

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.

Soybean oil000000970630
Corn oil000952.5472000
Maltodextrin 100004150600000
Mineral Mix #20000003500350000
Mineral Mix #2100250000000350
Calcium Carbonate040040000
Vitamin Mix #3000504104041040000
The AIN93G chow was replaced with the HFHC-C7 chow in the AIN93G group when the mice grew up (8 weeks old) to meet the energy needs of adulthood; the AIN93G group was thus renamed as AIN93G-HFHCC7 group. The HFHC chow remained unchanged in the WSD group.

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

  1. Western diet made TNBS induced colonic shortening and histopathological score slightly worse
  2. 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

Gene Pathways

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 IDPathwayNumber of Involved GenesUpregulation/DownregulationP Value
mmu04360Axon guidance28Up2.0E-04
mmu04261Adrenergic signaling in cardiomyocytes23Up9.8E-04
mmu05032Morphine addiction16Up1.9E-03
mmu00920Sulfur metabolism4Up3.4E-03
mmu04727GABAergic synapse13Up1.9E-02
mmu00512Mucin type O-glycan biosynthesis6Up1.9E-02
mmu04071Sphingolipid signaling pathway16Up2.8E-02
mmu04921Oxytocin signaling pathway19Up2.9E-02
mmu04020Calcium signaling pathway22Up2.9E-02
mmu04725Cholinergic synapse15Up2.9E-02
mmu04724Glutamatergic synapse15Up3.1E-02
mmu04728Dopaminergic synapse17Up3.4E-02
mmu04713Circadian entrainment13Up4.1E-02
mmu04976Bile secretion10Up4.8E-02
mmu04740Olfactory transduction167Down3.1E-15
mmu00790Folate biosynthesis8Down9.7E-04
mmu00380Tryptophan metabolism11Down1.2E-03
mmu04080Neuroactive ligand-receptor interaction38Down3.8E-03
mmu00480Glutathione metabolism12Down6.5E-03
mmu04726Serotonergic synapse19Down1.5E-02
Pathway ID stands for Pathway identifiers used in KEGG. When the WSD-TNBS group was compared to the AIN93G-HFHCC7-TNBS group, the later was the control group.

The metabolome

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

MetaboliteFormulaFold Change
Capric acidC10H20O23.93
cis-5-Dodecenoic acidC12H22O26.50
4-(2-Aminophenyl)-2,4-dioxobutanoic acidC10H9NO40.10
Undecanoic acidC11H22O22.90
10,13,16-Docosatriynoic acidC22H32O23.00
10-Hendecenoic acidC11H20O24.12
Lauric acidC12H24O25.65
Kynurenic acidC10H7NO30.34
10-[5]-ladderane-decanoic acidC22H34O20.18
Uridine monophosphate (UMP)C9H13N2O9P16.00
5Z,7E,9E,14Z,17Z-eicosapentaenoic acidC20H30O216.00
7-octenoic acidC8H14O20.17
Riboflavin (Vitamin B2)C17H20N4O60.47
4-Trimethylammoniobutanoic acidC7H16NO25.33
5-methyl-hexanoic acidC7H14O20.00
4-(2-Aminophenyl)-2,4-dioxobutanoic acidC10H9NO40.15
(25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oic acidC27H46O53.40
7Z, 10Z, 13Z, 16Z, 19Z-Docosapentaenoic acidC22H34O20.24
16-heptadecynoic acidC17H30O20.45
When the WSD-TNBS group was compared to the AIN93G-HFHCC7-TNBS group, the later was the control group.

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.

GeneMetabolitePearson correlation coefficientP value
Differential genes and metabolites in colonic tissue
Cyp11b15Z,7E,9E,14Z,17Z-eicosapentaenoic acid0.9279.162E-04
Cyp1a17-octenoic acid-0.9327.570E-04
Representative data from supplemental data for colonic tissue, the blood plasma data is not shown.

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.

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.

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:

  1. What if the control rats were fed a diet considered healthy for humans with “prebiotic” carbohydrates?
  2. What if the treatment group was given an inorganic sulfur compound like sulfate or sulfite?
  3. What changes could be happening to the microbiome?

1 thought on “Western Diet and Colitis”

Leave a Reply