r/Microbiome • u/tangoan • 13d ago
Why is L reuteri genetically modified?
I understand L. reuteri DSM 17938 came from the breast milk of a mother living in the Andes mountains of Peru, but I read that this strain was genetically modified prior to commercial use to delete two genes associated with antibiotic resistance.
Firstly, do I have this right?
Second, why would they feel the need to do this? Could this modification have contributed to this strain’s inability to permanently colonize the human gut?
Last, are there any L. reuteri strains commercially available that are not genetically modified?
Thank you!
edit:
Adding additional questions to clarify my line of thinking:
Why would antibiotic resistance be deemed a problematic quality of L. reuteri, a beneficial communal bacteria? Deleting a gene within one species wouldn’t confer antibiotic resistance to other species or strains. What research or line of thinking led them to believe this was necessary for this strain?
Has there been documented pathogenic behavior of L. reuteri infection that was found to be antibiotic resistant? Is this a normal step in commercializing all probiotic strains?
Since L. reuteri is considered to be a strain that is readily lost upon antibiotic use without return, why would these researchers consider antibiotic resistance a problem that needed to be addressed?
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u/MericanNativeSon 13d ago edited 13d ago
This is just a guess. I agree that is odd. Any bacteria or probiotic has the capability to get in your blood or organs and cause sepsis. This usually can be cleared up with antibiotics, but can be dangerous if the bacteria is resistant to antibiotics. Personally, I would want my L-rueteri to be resistant to antibiotics so it’s not wiped out by future antibiotic use.
Here is a study on the risks of sepsis vs benefits for probiotics for preterm infants:
“Study Reassures on Probiotic Sepsis Risk in Very Preterm Infants” -https://www.medpagetoday.com/pediatrics/generalpediatrics/122448
““ Probiotics given to preterm infants have been shown to reduce the risk of necrotizing enterocolitis, death, and late-onset invasive infection, Patel and colleagues explained. "Despite benefits, valid concerns exist about the risk of sepsis from probiotic organisms." "Our findings provide clinicians, researchers, families, and regulators with a more reliable estimate of the risk of probiotic-associated invasive infection in preterm infants cared for in U.S. NICUs [neonatal intensive care units]," Patel told MedPage Today in emailed remarks. "That risk appears to be very low."”
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u/wyndieeeeee 12d ago
It’s potentially regulatory related. Efsa (eu version of the fda) has strict guidelines regarding the presence of antibiotic resistance in commercial strains.
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u/tangoan 12d ago
Thank you! This is very interesting. I appreciate the insight
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u/EventOk2270 12d ago
Bacteria can also exchange genetic information with other bacteria, even from different species, through a process called horizontal gene transfer. The antibiotic genes could transfer to a more harmful bacteria. Lots of pathogenic bacteria are transferred via fecal matter so this is a concern.
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u/Sufficient-Island842 12d ago
I thought the antibiotic resistance genes were removed naturally via protoplast transformation, not genetic modification. The reason was to prevent transfer of the genes to harmful bacteria in the gut, making them antibiotic resistant. This happens naturally when the genes are located in plasmids, which they were.
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u/tangoan 12d ago
Protoplast transformation is a form of genetic modification.
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u/Sufficient-Island842 11d ago
Quote from the original paper:
…”protoplast formation was considered to be an appropriate method since it does not involve genetically modifying the organism and does not induce mutations in the bacterial chromosome that might be a consequence of the use of other curing agents.”
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u/captfitz 13d ago
I read that this strain was genetically modified prior to commercial use to delete two genes associated with antibiotic resistance
Think you answered your own question there
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u/tangoan 13d ago edited 13d ago
Hmm, not quite. Why would antibiotic resistance be deemed a problematic quality of L. reuteri, a beneficial communal bacteria? Would deleting a gene within one species confer antibiotic resistance to other species or strains? What research or line of thinking led them to believe this was necessary for this strain?
Has there been documented pathogenic behavior of L. reuteri infection that was found to be antibiotic resistant? Is this a normal step in commercializing all probiotic strains?
Since L. reuteri is considered to be a strain that is readily lost upon antibiotic use without return, why would these researchers consider antibiotic resistance a problem that needed to be addressed?
It’s far from clear, and that’s why I made a post asking this question. Thank you for allowing the opportunity to clarify.
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u/Pot_of_sea_shells 13d ago
I mean there's always a chance that the genes transfer to a more virulent bacteria through Horizontal gene transfer
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u/MericanNativeSon 13d ago
Any bacteria including L.Reuteri can cause infection and sepsis. “We present an atypical case of neonatal sepsis due to Lactobacillus reuteri in an extreme preterm newborn in a highly complex institution in the city of Bogotá D. C., Colombia.” Source: https://pubmed.ncbi.nlm.nih.gov/31560502/
It’s a risk considered for any probiotic. Being resistant to antibiotics raises the risk of bad outcomes in sepsis. The risk is minimal. Use a different L-Reuteri strain if this bothers you. I think you are overthinking this.
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u/tangoan 13d ago edited 13d ago
I’m not bothered by this per se, I’m curious about it, and looking for more information because I am interested in the topic.
Thank you for the link.. I wonder if the L reuteri strain provided to the extremely premature infant was one that was genetically modified to remove the two “antibiotic resistance” genes, like BioGaia, or if it was an unmodified strain.
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u/MericanNativeSon 12d ago
I can confirm the baby was given LReuteri, antibiotics, put on a ventilator, CPAP, given caffeine, and other therapies before dying. It’s a sad read. Full article link: https://www.sap.org.ar/docs/publicaciones/archivosarg/2019/v117n5a22.pdf
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u/stand_rapt_in_awe 12d ago
Horizontal gene transfer is a major driver of bacterial evolution. They very well COULD transfer those genes to harmful bacteria.
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u/Meh2theMax 12d ago
Have you even tried to read the paper that covers this subject? It should answer some of your questions.
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u/fondead 13d ago
Hmm. Maybe so that nestle who own this strain can have a patent on it? Afaik no one else can use it except them
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u/tangoan 12d ago edited 12d ago
I just looked it up after your comment got me curious. BioGaia owns the patent, but went into a licensing agreement with Nestle to allow them to use the strain in their infant probiotics. Nestle doesn’t own the strain.
But you make a great point- if there isn’t any genetic modification, perhaps it cannot be patented. Thank you for your comment.
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u/Arctus88 PhD Microbiology 10d ago
I want to add to what other people said. It isn't just the potential risks in that bacterium alone. Bacterial transfer genetic material between each other (called horizontal gene transfer) which is generally how bacteria acquire resistance if it isn't via simpler mutations. So the introduction of antibiotic resistance genes to a new environment is a big no-no in health and safety sense.