The world of microbes that live in the human intestine can have far-reaching effects on human health. Multiple diseases, including inflammatory bowel disease (IBD), are related to the balance of these microbes, suggesting that its proper restoration it could help treat the disease.

According to the ACCU Confederation (crohn and ulcerative colitis), IBD “encompasses two pathologies, ulcerative colitis and the Crohn’s disease. In Spain, the former is more frequent than the latter (58% versus 42%), and this difference is expected to increase slightly in the coming years. Both are characterized by being essentially intestinal diseases, immune-mediated, inflammatory and chronic, that evolve in outbreaks (active phases) and periods of remission (inactive phases). Both alter the body’s ability to digest food and absorb nutrients, and also share clinical and pathological characteristics. Some common symptoms are: diarrhea, blood in the stool, tiredness, abdominal pain, loss of appetite, weight loss, and fever. ”

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Although there are also clinical and pathological differences between the two. “For example, the area of ​​involvement. Ulcerative colitis is characterized by inflammatory lesions chronicles in the wall of the large intestine (colon), while crohn can appear anywhere in the digestive system (from the mouth to the anus). You can only have one or the other, not both at the same time. In cases where there are doubts as to which of these two diseases causes inflammation, the term indeterminate colitis is used, “adds the institution.

The recommendations

Photo: iStock.
Photo: Photo: iStock.
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Therefore, treatment with probiotics as an adjunct to conventional treatment is associated with a reduction in adverse events in patients with IBD. Those patients who take probiotics for 75% or more of the course of their disease may experience a significant decrease in probiotics related to the disease, both in crohn’s and ulcerative colitis. The specific type of probiotic or blend, the optimal amount and exact duration of treatment are details as yet unknown. More studies are required to define the exact recommendations in clinical practice.

The new probiotic

Many probiotics (live yeast or bacteria) currently on the market have been optimized through evolution in the context of a healthy gut. However, to treat complex diseases like IBD, a probiotic should serve many functions, including the ability to turn off inflammation, reverse damage, and restore the gut microbiome. Given all these needs, researchers at Brigham and Women’s Hospital (USA) have developed a ‘designer’ probiotic, a carefully designed yeast that can induce multiple effects for the treatment of IBD. The preclinical results of their work are published in ‘Nature Medicine’.

We have taken yeast, the same that is used to make beer, and we’ve given it the ability to detect inflammation and secrete an anti-inflammatory molecule, “said the corresponding author, Francisco Quintana, a researcher at the Ann Romney Center for Neurological Diseases at Brigham. “We call this new platform Y-bots (yeast robots) and we see the potential here to develop therapies that can treat intestinal tissue diseases and more, “admits the lead researcher.

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Previous research from Quintana’s laboratory has helped to clarify the connection between the intestine and diseases that affect the brain, suggesting potential applications for probiotic engineering beyond IBD.

Modified brewer’s yeast

Quintana and his colleagues developed their probiotic utilizando Saccharomyces cerevisiae, a kind of yeast used in winemaking, baking, and brewing. Using CRISPR / Cas9 gene editing technology, The researchers introduced genetic elements that could detect inflammation and respond to it by secreting an enzyme that can degrade a key molecule involved in inflammation. Modified yeast can secrete different levels of enzyme, depending on the amount of inflammatory signal present at a site in the intestine. This means that the probiotic can have a very localized response to inflammation. In mice, the modified yeast successfully suppressed gut inflammation, reduced fibrosis, and restored a balanced gut microbiome.

For this new therapeutic platform to be applied to IBD and other diseases in humans, Quintana and his team must carry out safety studies. They also plan to further refine and test engineered yeast to see if it can speed up tissue repair. Beyond IBD, the team plans to investigate the use of probiotics designed to treat a common side effect of cancer immunotherapy, colitis.

We want to use the tools of synthetic biology to design what can be found in nature “, they review. “When designing probiotics, our goal is to create more personalized medications, localized and highly controlled to treat diseases of the gut and more. ”

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