Gut bacteria turn dietary phytate into health-boosting fatty acids, study shows

In a recent study published in the journal Nature Microbiology, researchers investigated how the human gut bacteria metabolize dietary phytate.

Phytate is abundant in the plant kingdom, especially rice, wheat, and nuts. Due to its metal-chelating properties, it is recognized as an antinutrient in animal feed. However, there is no evidence that phytate might cause problems in humans. Conversely, plant-based diets, including phytate-rich seeds and nuts, have health benefits.

Study: Phytate metabolism is mediated by microbial cross-feeding in the gut microbiota. Image Credit: Manee_Meena / Shutterstock

Dietary phytate supplementation has been shown to promote epithelial repair, improve glucose metabolism, and reduce inflammation. However, the underlying molecular mechanisms are elusive. Phytate is involved in insulin signaling, glucose metabolism, cancer metastasis, and cell migration. It is synthesized during intracellular myoinositol metabolism and is among the most abundant inositol phosphates (InsPs) in mammals.

However, it is unclear whether dietary phytate could enter the systemic circulation and contribute to endogenous inositol polyphosphate biosynthesis. Previously, the authors reported the conversion of phytate into short-chain fatty acids (SCFAs) by the human gut microbiome, but the gut microbes responsible for conversion were unknown.

The study and findings

In the present study, researchers evaluated the metabolism of dietary phytate by the human gut microbiota. First, they incubated fecal samples from two donors (A, B) in a ¹³C₆ InsP₆-supplemented medium. Supernatants were collected and used for ¹³C-nuclear magnetic resonance (NMR). Besides, non-labeled fecal enrichments were transferred to fresh phytate media.

The fecal microbiome of donor A metabolized ¹³C₆ InsP₆ to ¹³C₂ acetate and ¹³C₃ 3-hydroxypropionate within a few hours to ¹³C₃ propionate after 24 hours. On the other hand, the fecal microbiome of donor B slowly metabolized ¹³C₆ InsP₆ to ¹³C₂ acetate and ¹³C₄ butyrate. Next, the genomic DNA from the third non-labeled phytate enrichment was isolated for sequencing.

This revealed the enrichment of two distinct microbial communities: Ruminococcaceae, Butyricicoccus, and Mitsuokella were the most abundant in donor A, whereas Mitsuokella, Escherichia coli/Shigella, and Butyricicoccus were the most abundant in donor B. The relative abundance of most species declined at the end of phytate incubation; however, it increased for Mitsuokella spp. in both enrichments. M. jalaludinii was the predominant species.

Next, the team analyzed the microbiome of over 6,000 people from a general population cohort (HELIUS). They identified three amplicon sequence variants of Mitsuokella that were similar to those of M. jalaludinii or M. multacida. Most people harbored M. jalaludinii; males had the highest prevalence. Next, the researchers isolated an M. jalaludinii strain from donor A, growing rapidly on phytate.

Its genome was similar to a type-strain DSM13811^T and had highly similar phytate degradation pathway genes. Next, M. jalaludinii DSM13811^T was cultured in a medium with myoinositol or phytate. It grew rapidly in the phytate medium, doubling in 3.4 hours, compared to 7 hours in the myoinositol medium. However, metabolite production remained similar between conditions.

Next, the team cultured M. jalaludinii in a bicarbonate-buffered medium with ¹³C₆ myoinositol or ¹³C₆ phytate. It rapidly converted phytate into several metabolites, and 3-hydroxypropionate, lactate, and succinate were the main end metabolites. The accumulation of myoinositol and myoinositol-2-monophosphate confirmed them as the intermediates of phytate degradation.

Furthermore, the use of ¹³C₆ myoinositol by M. jalaludinii was also confirmed, with its conversion into 3-hydroxypropionate, succinate, and lactate. Transcriptomic analyses revealed increased expression of inositol transporter, ATP synthase, and high-affinity phosphate transport system genes, among others, during growth in the phytate medium. Besides, the periplasmic phytase gene was constitutively expressed.

Next, the team examined the synergy between Anaerostipes rhamnosivorans and M. jalaludinii in phytate degradation, given that the supplementation of A. rhamnosivorans in fecal phytate enrichments has been shown to elevate propionate formation. Acetate and propionate were detected in co-cultures, but lactate and 3-hydroxypropionate accumulated only in the M. jalaludinii monoculture. The synergy was due to an interspecies transfer of 3-hydroxypropionate.

However, A. rhamnosivorans had a limited effect on phytate dephosphorylation by M. jalaludinii. Finally, in vivo synergy between the two species was evaluated in mice gavaged with M. jalaludinii only, both bacterial species, or a sterile control and challenged with ¹³C₆ InsP₆. Cecal ¹³C₆ InsP₆ levels were significantly reduced three and six hours later.

Colonic levels of M. jalaludinii were increased in bacteria-treated groups, while those of A. rhamnosivorans levels were elevated in the co-treatment group only. Notably, the difference in InsP₆ levels was smaller at six hours, indicating InsP₆ degradation by residual murine microbiome. Propionate accumulation was not significantly different between bacteria-treated mice and controls. Cecal levels of ¹³C 3-hydroxypropionate were significantly increased in the M. jalaludinii group.

Conclusions

The researchers showed that the human gut microbiome can convert phytate into different SCFAs predicated on microbial composition. Mitsuokella spp. was identified as a prevalent and efficient phytate degrader in the gut. Further, the study revealed the synergistic interactions between A. rhamnosivorans and M. jalaludinii via 3-hydroxypropionate, leading to propionate production. Overall, the findings may promote strategic approaches to leverage microbial synergy and phytate for beneficial health interventions.