Vitamin B1 (Thiamine)

The biosynthesis pathway of vitamin B1 or thiamine, is a metabolic process by which certain bacteria of the intestinal microbiome produce thiamine, an essential micronutrient for cellular energy metabolism. This vitamin of microbial origin can be directly absorbed by the host at the colonic level. Furthermore, microbial loss of this synthesis capacity can affect the microbial ecosystem.

Certain bacteria in our gut are capable of synthesizing vitamin B1 (thiamine) from scratch. This process is carried out through two independent pathways that generate precursor molecules (called HET-P and HMP-PP). These branches converge in a final step, where specific enzymes combine them to give rise to the functional form of the vitamin (thiamine monophosphate). With the exception of Firmicutes, several bacterial phyla synthesize thiamine monophosphate, especially, Bacteroidetes and Fusobacteria.

External factors, such as a deficient diet or prolonged use of medications, can alter the population of these producing bacteria and, consequently, reduce the levels of available thiamine. This scarcity not only affects energy production in our colon, but also alters the survival of beneficial bacteria that depend on this supply, breaking the balance of the ecosystem.

At the cellular level, thiamine is an indispensable cofactor for critical enzymes involved in carbohydrate metabolism and energy production (ATP), such as pyruvate dehydrogenase. Constant biosynthesis by our microbiota ensures a direct supply in the colon. There, colonocytes efficiently absorb it through specific membrane transporters (such as THTR-1 and THTR-2) to meet their high energy demands.

However, the impact of this vitamin goes far beyond nourishing our cells. Local thiamine is vital for other beneficial gut bacteria (such as Faecalibacterium) to produce short-chain fatty acids (SCFAs), especially butyrate. This compound is one of the greatest protectors of the gut: it reduces inflammation and strengthens the mucosal barrier.

The evaluation of de novo thiamine biosynthesis is performed by Shotgun metagenomic sequencing, quantifying the overall genetic potential of the metabolic pathway in your gut ecosystem. Our bioinformatic algorithm tracks and maps the abundance of genes and operons that make up the thiamine pyrophosphate biosynthesis superpathway. We specifically look for the potential expression of key and limiting genes such as thiC (pyrimidine moiety synthase) and thiG (thiazole moiety synthase), as well as thiD and thiE.

On an ecological level, de novo B1 synthesis is an expensive metabolic "luxury." Species capable of carrying out this complete process belong mostly to the phylum Bacteroidetes (e.g., Bacteroides fragilis, Prevotella copri) and certain Proteobacteria and Fusobacteria. The vast majority of bacteria in the phylum Firmicutes lack this complete machinery.

High capacity reflects a robust and collaborative trophic network. The ecosystem is self-sufficient in energy and prevents the collapse of auxotrophic bacteria that produce short-chain fatty acids. However, low capacity signals ecological vulnerability ("metabolic fragility"). The ecosystem critically depends on the dietary intake of thiamine. Intervention: The clinical strategy requires optimizing the diet (increasing consumption of sunflower seeds, macadamia nuts, legumes) and considering oral supplementation with Vitamin B1 (e.g., Benfotiamine) to ensure that neither the host nor beneficial bacteria enter an energy deficit, supporting with prebiotics to stimulate the phylum Bacteroidetes.