In my last post on MRI Scans, I felt the best model is based on Evidence of widespread metabolite abnormalities in Myalgic encephalomyelitis/chronic fatigue syndrome: assessment with whole-brain magnetic resonance spectroscopy [2020]. Metabolite abnormalities can be a direct result of microbiome dysfunctions. Those abnormalities are very treatable using microbiome tests and expert systems such as generated by Microbiome Prescription.

What are Metabolites?

Metabolites are substances made or used in the body during metabolism, which is the process of breaking down food or chemicals into energy and other useful materials. They help the body grow, repair itself, and function properly. Examples include amino acids, vitamins, and sugars.

Example for ME/CFS

In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), metabolites have been found to play a critical role in understanding the disease’s mechanisms and symptoms:

1. Gut Microbiome and Butyrate: ME/CFS is associated with changes in gut bacteria, leading to reduced levels of butyrate, a metabolite produced by certain gut microbes. Butyrate supports gut health, immune regulation, and energy production. Reduced butyrate levels in ME/CFS patients are linked to fatigue severity and inflammation.
2. Energy Metabolism: Studies reveal abnormalities in pathways like fatty acid metabolism, glucose metabolism, and the citric acid (TCA) cycle in ME/CFS patients. These changes suggest impaired cellular energy production, contributing to chronic fatigue.
3. Amino Acid Metabolism: Altered tryptophan metabolism and disruptions in the kynurenine pathway have been observed, which may affect immune function and contribute to neurocognitive symptoms through the gut-brain axis.
4. Plasma Metabolites: ME/CFS patients exhibit differences in plasma metabolites compared to healthy controls, particularly after physical exertion. These include disruptions in glutamate metabolism, which may impact recovery and exacerbate symptoms.
5. Disease Subtypes: Metabolomic studies have identified distinct metabolic profiles among ME/CFS patients, suggesting subtypes with different clinical presentations and underlying mechanisms.

These findings highlight the importance of metabolites in ME/CFS research, offering potential biomarkers for diagnosis and targets for therapeutic interventions.

Example for IBS

In the context of Irritable Bowel Syndrome (IBS), metabolites play a significant role:

1. Gut microbiota-derived metabolites: These are substances produced by the bacteria in our intestines and are thought to be involved in IBS symptoms. Some important examples include:
   • Bile acids
   • Short-chain fatty acids
   • Vitamins
   • Amino acids
   • Serotonin
   • Hypoxanthine
2. Blood metabolites: Certain metabolites in the blood have been found to have a causal relationship with IBS. For example:
   • Stearate: Associated with decreased susceptibility to IBS
   • Arginine: Associated with increased risk of IBS
   • 1-palmitoylglycerol: Associated with increased risk of IBS
3. Fecal metabolites: Studies have identified specific fecal metabolite profiles in IBS patients that differ from healthy individuals. These metabolites are often amino acids or fatty acids.
4. Brain-gut interaction: Some metabolites, particularly amino acids like tryptophan, glutamate, and histidine, may influence brain function in IBS patients5. They could affect brain connectivity either directly by crossing the blood-brain barrier or indirectly through peripheral mechanisms.

Understanding these metabolites and their interactions with the gut microbiome may provide valuable insights into the underlying mechanisms of IBS and potentially lead to new diagnostic tools or treatments.

Enzymes Role to Metabolites

Enzymes play a crucial role in managing metabolites within our bodies. Here’s a simple description of their relationship:

1. Enzymes are proteins that act as biological catalysts7. They speed up chemical reactions in our cells without being used up themselves.
2. Metabolites are substances produced or used during metabolism1. They can be small molecules like sugars, amino acids, or fatty acids.
3. Enzymes help break down large molecules (like proteins, fats, and carbohydrates) into smaller metabolites. This process is essential for digestion and energy production.
4. Enzymes also help build larger molecules from smaller metabolites. This is important for creating cellular structures and storing energy.
5. Each enzyme typically works on specific metabolites, called substrates1. The enzyme and substrate fit together like a lock and key.
6. By controlling which reactions happen and how quickly, enzymes regulate the levels of various metabolites in our bodies. This helps maintain balance and allows cells to respond to changing needs.

In essence, enzymes are the workers that manage metabolites, ensuring our bodies can efficiently use the food we eat and carry out the chemical processes necessary for life.

Data From Samples Uploaded with ME/CFS

It happens that from uploaded samples and KEGG: Kyoto Encyclopedia of Genes and Genomes; we can determine that the following enzymes are (VERY VERY) statistically significant. The most significant ones are all too high. The top ones comes from the three genus only: Chlorobaculum , Pelodictyon and Prosthecochloris

• Chlorobaculum limnaeum
• Chlorobaculum parvum
• Chlorobaculum tepidum
• Chlorobium chlorochromatii
• Chlorobium limicola
• Chlorobium phaeobacteroides
• Chlorobium phaeovibrioides
• Chloroherpeton thalassium
• Pelodictyon luteolum
• Pelodictyon phaeoclathratiforme
• Prosthecochloris aestuarii
• Prosthecochloris sp. CIB 2401
• Prosthecochloris sp. GSB1
• Prosthecochloris sp. HL-130-GSB

Some (but not all) enzymes can be provided by some probiotics. Below is recent feedback from a person dealing with a child’s autism.

EC Key	Enzyme Name	Probability	Shift
1.1.1.325	sepiapterin reductase (L–threo-7,8-dihydrobiopterin forming)	1.61685e-015	high
2.1.1.331	bacteriochlorophyllide d C-121-methyltransferase	1.61685e-015	high
2.1.1.332	bacteriochlorophyllide d C-82-methyltransferase	1.61685e-015	high
2.1.1.333	bacteriochlorophyllide d C-20 methyltransferase	1.61685e-015	high
3.1.1.100	chlorophyllide a hydrolase	1.61685e-015	high
4.2.1.169	3-vinyl bacteriochlorophyllide d 31-hydratase	1.61685e-015	high
2.3.3.8	ATP citrate synthase	1.18208e-013	high
1.3.1.75	3,8-divinyl protochlorophyllide a 8-vinyl-reductase (NADPH)	5.353e-013	high
2.5.1.42	geranylgeranylglycerol-phosphate geranylgeranyltransferase	7.71322e-013	high
1.17.98.2	bacteriochlorophyllide c C-71-hydroxylase	2.69579e-012	high
2.7.8.36	undecaprenyl phosphate N,N′-diacetylbacillosamine 1-phosphate transferase	3.60014e-009	low
1.11.1.6	catalase	1.37633e-008	low
6.5.1.8	3′-phosphate/5′-hydroxy nucleic acid ligase	1.02548e-007	low
2.5.1.105	7,8-dihydropterin-6-yl-methyl-4-(β-D-ribofuranosyl)aminobenzene 5′-phosphate synthase	1.27364e-007	low
1.1.1.65	pyridoxine 4-dehydrogenase	1.89183e-007	high
2.6.1.59	dTDP-4-amino-4,6-dideoxygalactose transaminase	3.34948e-007	low
4.1.1.31	phosphoenolpyruvate carboxylase	4.73602e-007	high
5.4.99.26	tRNA pseudouridine65 synthase	5.94186e-007	high
1.1.1.127	2-dehydro-3-deoxy-D-gluconate 5-dehydrogenase	8.09119e-007	low
3.4.21.83	oligopeptidase B	8.612e-007	high
1.1.1.9	D-xylulose reductase	1.07212e-006	high
1.12.1.4	hydrogenase (NAD+, ferredoxin)	1.22627e-006	high
3.5.2.9	5-oxoprolinase (ATP-hydrolysing)	1.30156e-006	high
2.7.1.12	gluconokinase	1.49961e-006	high
1.6.1.2	NAD(P)+ transhydrogenase (Re/Si-specific)	3.05641e-006	high
7.1.1.1	proton-translocating NAD(P)+ transhydrogenase	3.05641e-006	high
3.1.1.114	methyl acetate hydrolase	3.98055e-006	low
3.2.1.165	exo-1,4-β-D-glucosaminidase	4.31375e-006	low
2.3.1.117	2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase	4.31566e-006	high
2.7.8.12	teichoic acid poly(glycerol phosphate) polymerase	4.59165e-006	low
6.1.1.13	D-alanine—poly(phosphoribitol) ligase	4.88544e-006	low
1.12.98.4	sulfhydrogenase	6.48299e-006	low
4.2.1.22	cystathionine β-synthase	7.49383e-006	high
2.3.1.78	heparan-α-glucosaminide N-acetyltransferase	8.1071e-006	low