The new study warns long -term risks from germ transplants

The transplants of germ faeces (FMTs) have been offered as a possible treatment for various conditions, from inflammatory bowel diseases, obesity and type 2 diabetes in autism. However, new research from the University of Chicago warns against the widespread FMT use due to the possibility of long -term, unintentional health consequences for the recipients.

The FMT involves the transfer of germs to the stool from a healthy person to a sick person, hoping to restore a healthy balance in the microbial intestine. Since stools mainly contain anaerobic germs from the colon (that is, they cannot tolerate oxygen), FMT can cause mismatches in the intestinal ecosystem when these bacteria colonize the small intestine and other parts of the digestive system.

In experiments with mice and studies with human tissue samples, researchers who conducted the new study saw that anaerobic germs from the colon not only colonize the small intestine after a transplant, but also insisted there for months. These germs also changed their new intestinal environments to their benefit, “TerraForming” in ways that caused changes in the recipient’s metabolism, behavior and energy balance.

“I think it’s a part of an awakening call in the field that we may not have to put small germs in different parts of the intestine that should not be there,” said Orlando (Landon) Deleon, PhD, Postdoctoral Researcher at Uchicago and Leader Cell. “If we are planning good therapeutic, we should be aware of the importance of corresponding to the regional germ in their right environment so that we can better provide overall health benefits.”

A huge and varied ecosystem

FMT is approved by the Food and Drug Administration only for the treatment of repeated infections with Clostridium difficile (C. Diff)An opportunistic bacterium that often causes severe gastrointestinal symptoms and inflammation in antibiotic hospital patients. Seeing success in treatment C. Difference Patients, many doctors were willing to use FMT to treat other digestive conditions. Researchers understand that gut microbial health can affect all vital organs and body systems, so the idea is that replacing a “sick” gut with a “healthy” germ could correct the problem on a swoop.

The intestine is not just a consistent environment with the same microbiotic throughout, however. Instead, it has several separate areas that are very different microbial ecosystems, each adapted to specific germs that can provide vital functions for their host health.

There are germs along the entire intestinal road and we mainly study its last third (the colon). So how can you expect a FMT, with germs from one -third of the intestinal road at the end, to correct the rest of the gut? ”

Orlandon (Landon) Deleon, PhD, Postdoctoral Researcher at Uchicago and Head Author of New Study

To test the FMT effects on various parts of the intestine, Deleon, Eugene B. Chang, MD, Medical Professor Martin Byer in Uchicago and a higher author of the study and their team conducted a series of mice experiments. A group of mice received a germ transplant received from the bat, the first part of the small intestine. A second group received a standard FMT and a third group received a transplant from Cecum, a section that connects the small and colon, which has a mixture of germs from both.

FMT recipients are usually treated with antibiotics first to clean the germs living in the gut, leaving a pure slate for newly acquired germs to install – sometimes, however, in the wrong places. Tests have shown that germs from each of these transplants successfully colonize the entire intestinal tract in mice, not just in their intrinsic niches. This has created regional intestinal mismatches that insist for up to three months after a single transplant.

Modified microbials have also changed the production of metabolites in each intestinal area, which may affect the host health. Researchers saw changes in liver metabolism, including activity in immune -related genes. They also observed differences in behaviors, activity and energy expenditure in mice after transplants.

The most striking finding was that the existence of the incorrect germs in the wrong place was reformed the identity of the tissue to make it more appropriate for them. Deleon saw that mismatches changed the expression of genes and proteins in the intestinal lining in ways that looked more like the levels of expression from the original or indigenous intestinal areas of the germs.

“It’s like being mechanical or shaping their environment to help them fit,” Deleon said.

An approach ‘OMNI-MICROBIAL’

Chang said that this research underlines the need for greater attention with FMT before fully understanding the long -term effects of introducing a set of germs into a new environment.

“We have absolutely no idea what’s on FMT, except that it’s a combination of germs,” ​​Chang said. “But even a single FMT will cause a change in host-microbi relationships in these very different areas of the intestine that can be very difficult to reverse.”

Both Deleon and Chang support “Omni-Microbial Transplants”, or OMT, instead. This approach will carry the germs taken from all the different areas of the intestine, not just those of the colon. Whether given through endoscopy or pill form, the germs are naturally installed at the right points, especially when they compete side by side with others who usually reside in a particular area.

“If there is an open space, something will be filled,” Deleon said. “But the germs that had to be there are better right for it, so that they will of course be filled with even the presence of other germs.”

Deleon plans to continue to study how different germs exert their influence on different parts of the intestine, using different approaches such as the sequence of a cell and metabolic to watch their activity. It also examines how the areas of the gut deformed by germs can be restored in their original state, which could help restore normal bowel function. This deeper understanding could lead to improvements in the implementation of microbial transplants, ultimately helping to meet their significant promise.

The study, “regional germs from germ transplants that promote persistently, out -of -the -host consequences”, was supported by the National Institute of Health/National Institute of Diabetes and Diabetes and Kidney Disease of Diseases and the UC.

Additional authors include Mora Mocanu, Candace M. Cham, Alan Tan, Ashley M. Sidebottom, Jason Koval, Hugo D. Ceccato, John J. Colgan, Marissa M. St. George, Joash M. Lake, Michael Cooper, Jingwen Xu and David T. Rubin from Uchicago. Julia Moore and Kristina Martinez-Guryn from Midwestern University. and Zhilu XU, SIEW C. NG, Francis Kl Chan, Hein M. Tun and Qi su from the Chinese University of Hong Kong.