by University of Gothenburg

Co-isolation and cross-feeding of F. prausnitzii and D. piger in vitro. a, Co-culture of F. prausnitzii DSM 32186 and D. piger DSM 32187 on PGM plates without supplementation of glucose or acetate. b, Gram staining of colonies from isolation of F. prausnitzii DSM 32186 and D. piger DSM 32187. Arrows indicate F. prausnitzii (long fusiform rods) (1) and D. piger (short rods) (2). Scale bar, 10 μm. c, Dendrogram illustrating the relationship between D. piger DSM 32187 and related genomes. d, Dendrogram illustrating the relationship between F. prausnitzii DSM 32186 and related genomes. e, The number of colony-forming units of F. prausnitzii DSM 32186 in monoculture and in co-culture with D. piger DSM 32187 under anaerobic conditions in mPGM (PGM containing 25 mM of glucose) for 24 h. P = 0.0003. f, Metabolite profiles of F. prausnitzii DSM 32186 and D. piger DSM 32187 cultivated as monocultures or co-culture under anaerobic conditions in mPGM medium for 24 h. Glucose: P = 0.0000031 (F. prausnitzii + D. piger versus D. piger), P = 0.0000038 (F. prausnitzii + D. piger versus F. prausnitzii); lactate: P = 0.0000001 (F. prausnitzii + D. piger versus D. piger), P = 0.0000005 (F. prausnitzii versus D. piger), P = 0.00014 (F. prausnitzii + D. piger versus F. prausnitzii); acetate: P = 0.0000004 (F. prausnitzii + D. piger versus D. piger), P = 0.0000003 (F. prausnitzii versus D. piger); butyrate: P = 0.000001(F. prausnitzii + D. piger versus D. piger), P = 0.0000031 (F. prausnitzii + D. piger versus F. prausnitzii). ‘mM change’ on the y axis indicates the difference in concentration from the inoculated medium at baseline. g, Schematic of the suggested cross-feeding between F. prausnitzii and D. piger as co-culture in mPGM. n = 3 independent experiments, ***P < 0.001 determined by two-tailed t-test (e) or one-way ANOVA (f). Data are mean ± s.e.m. Credit: Nature (2023). DOI: 10.1038/s41586-023-06378-w

One of the beneficial gut bacteria residing in the human gut, which normally cannot survive in an environment with oxygen, can now be made oxygen-tolerant. This is a key finding in the development of future probiotic treatment that is now being explored to improve glucose control in individuals with prediabetes.

Our intestines are home to trillions of bacteria, the gut microbiota, which are important for functions such as digesting food and educating and activating the immune system. During the past decade it has been clarified that changes in the bacterial composition can be linked to various diseases.

Significant expectations have been attributed to the next generation probiotics, or live bacteria products, which can replace the missing bacteria in individuals with increased risk of developing diseases. However, a significant problem has been to overcome the bacteria's oxygen sensitivity, since the vast majority are strictly anaerobic. With bacteria dying just seconds after being exposed to oxygen in the air, it has been hard to develop live bacterial cultures of extremely oxygen sensitive bacteria.

A naturally occurring symbiosis

In a paper published in the journal Nature, researchers from the University of Gothenburg and the probiotic company BioGaia AB report how they have overcome the oxygen sensitivity of an anti-inflammatory gut bacterium, Faecalibacterium prausnitzii, which is significantly reduced in conditions including type 2 diabetes and cardiovascular disease.

In their study, Faecalibacterium prausnitzii was co-isolated with another bacterium, Desulfovibrio piger, which has beneficial effects on Faecalibacterium prausnitzii growth and function. By subsequently "training" the oxygen-sensitive bacteria in a favorable electrochemical environment, the researchers were able to isolate more oxygen-tolerant Faecalibacterium prausnitzii.

The team's leader, Professor Fredrik Bäckhed, explains, "By combining a naturally occurring symbiosis with 'training' of the bacteria, we have established a new strategy for producing otherwise oxygen-sensitive bacteria as live biotherapeutic products, which could prevent diseases when these bacteria are reduced in number."

Studying the impact on sugar control

The first author of the study is Muhammad Tanweer Khan, a researcher in Professor Bäckhed's team who previously discovered this symbiosis. He also represents the probiotic company BioGaia AB, which helped to develop the bacteria for the proposed dietary supplement.

"When these bacteria were grown together, both the biomass—in other words, the number of bacteria—and the production of butyrate, which has an anti-inflammatory effect, increased," he says. "This will enable us to increase the production yield, and to potentially increase butyrate production in the future."

The study shows that the combination of bacteria is safe for human consumption. The next step will be a study to investigate how supplementation with these bacteria may affect sugar control in individuals with prediabetes.

"We have high hopes," concludes Professor Bäckhed. "Further studies will show if we are correct in our hypothesis that gut bacteria have the potential to improve our health."

More information: Fredrik Bäckhed, Synergy and oxygen adaptation for development of next-generation probiotics, Nature (2023). DOI: 10.1038/s41586-023-06378-w

Provided by University of Gothenburg