Innovation: Transplantation of fecal microbiota prolongs the life of prematurely aging mice
Bárcena et al. / Nature Medicine, 2019

Transplantation of fecal microbiota and oral administration of bacteria Akkermansia muciniphila prolonged the life of mice with progeria (premature aging) and improved their health. Scientists resorted to such interventions after studying the intestinal microflora of mice and people with progeria and comparing it with the microflora of long-livers. Article published in Cenforce 100 Medicine –

A number of health effects of intestinal microbiota are currently known.. So, in mammals, it affects the feeling of fullness, can protect against pathogens, is involved in the digestion and synthesis of vitamins, secondary bile and short chain fatty acids. Its association with obesity , type 2 diabetes , cardiovascular disease , non-alcoholic fatty liver disease , cancer, and the response to anti-cancer therapy is known . 

Previously, scientists investigatedthe profile of the intestinal microbiota in long-livers, but its changes in the syndromes of premature aging and the effect on such conditions have not been described. Progeria refers to very rare genetic disorders that show signs of aging at a very young age. The most studied Hutchinson-Guildford Progeria Syndrome (HCH) is inherited in an autosomal dominant manner. 

Clea Bárcena from the University of Oviedo in Spain and her colleagues set out to find out if there are specific dysbioses in the intestines that can be associated with progeroid syndromes, and what effect on mice with progeria may have changes in their microbiome.

First, scientists decided to figure out how relevant the indicator is the profile of the intestinal microbiota during progeria, whether it is possible to distinguish its characteristic features. To do this, they conducted studies on mice and humans. They compared the metagenomes of bacteria living in the intestines of LmnaG609G / G609G mice (SPHG model) and wild-type mice. In the first month of life, the data of both groups of mice were similar, but noticeable differences were found from the fourth. For example, in rapidly aging mice, the number of bacteria of the genera Akkermansia and Dehalobacterium decreased against the background of an increase in the number of proteobacteria and cyanobacteria. The scientists obtained similar results by repeating the study on mice Zmpste24 – / – (another model of CNG).

Further, the authors checked whether specific dysbiosis in the intestine is detected in patients with progeria. They studied the feces of four children with CNS and their healthy brothers and sisters, and also studied the fecal microbiome of a child with Nestor-Guillermo syndrome and his family. Despite the small number of samples, the results suggested that the environment has a greater effect on the intestinal microbiome than progeria. Further analysis showed a decrease in the number of bacteria of the genus Gemmige and an increase in the number of a number of clostridia. Scientists have concluded that dysbiosis worsens over time in both mice and people with progeria.

Scientists have suggested that people with exceptional lifespan may be carriers of a microbiome that can improve the health of others. Their findings are consistent with previous studies: in centenarians, they found large numbers of Akkermansia and Christensenellaceae bacteria and low levels of proteobacteria compared to controls. 

Further, scientists established whether mice with progeria will live longer if they change their microbiome. In this part of the work of Lmna-G609G micedivided into four groups of 11 individuals. Mice from the treatment group underwent transplantation of fecal microbiota (TFM) from healthy wild-type mice. In the control group were animals that were not subjected to any intervention. Mice of the third group received TFM from older LmnaG609G / G609G mice, and a microbiota transplant was simulated in the fourth group. 

Sick mice that received bacteria from healthy ones showed an improvement, progeria slowed down. This was manifested by a slowdown in weight loss, normalization of blood glucose levels, as well as a mitigation of some other symptoms. Most importantly, the mice from the treatment group lived on average 13.5 percent longer than the control (160 days versus 141 days).

Innovation: Transplantation of fecal microbiota prolongs the life of prematurely aging mice
The survival rate of LmnaG609G / G609G mice (red graph), Lmna-G609G mice after TFM from wild-type mice (green graph), and Lmna-G609G mice after TFM from old Lmna-G609G mice. 
Bárcena et al. / Nature Medicine, 2019

In the third group, transplantation did not lead to accelerated aging, but the mice showed metabolic disorders: they spent less energy and gained weight, they had higher blood glucose levels. Similar results were obtained on Zmpste24 – / – mice . 

A study of intestinal metagenome in both mice and humans has shown a decrease in the amount of A. muciniphila in premature aging syndrome. In addition, previously in animal experiments, the use of this bacterium positively affected the metabolism andimproved response to immunotherapy. Therefore, scientists found it advisable to check whether the appointment of A. muciniphila can improve the health of Lmna-G609G mice and prolong their life. The increase in life expectancy compared with the control in this case was slightly less than with TFM, on average, no more than 10 days. According to scientists, this indicates the protective role of the microorganism in accelerated aging. They explain this effect by increased expression of the Reg3g gene , thickening of the intestinal mucosa and improvement of its healing.

To clarify other possible mechanisms behind improving the health of mice and increasing their lifespan after TFM, scientists profiled the intestinal microbiota metabolome of wild-type mice, Lmna-G609G mice, and Lmna-G609G mice that received the transplant. After analyzing the differences, the authors suggested that enhancing the synthesis of secondary bile acids may play a positive role. 

Heidi Zapata from Yale University, which studied the microbiome of people with aging and age-related pathologies, calledthe study is interesting, but cautioned against prematurely projecting its results onto people. “I do not think that we are close to finding a pill that we could swallow. But given the importance of the microbiome, this portends future opportunities, ”she said. 

Earlier in a small study, scientists showed that oral administration of A. muciniphila in humans can reduce the risk of heart disease and diabetes in the metabolic syndrome. Scientists also described changes in the microbiome with fibromyalgia and demonstrated amelioration of autism symptoms in a small group of children who received TFM.