The mouse data, published in Science Translational Medicine, could open new doors to fight age-related skeletal muscle loss by altering the microbial make up in our gut.
Led by Professor Sven Pettersson from the Nanyang Technological University Singapore (NTU Singapore) the international research team reveal that mice with gut microbes had stronger skeletal muscles that can produce more energy when compared to mice without any gut microbes, known as germ-free mice.
Further, they identified genes and signalling pathways involved in the regulation of skeletal muscle mass and function that responded to cues from the gut microbiota.
"These results further strengthen the growing evidence of gut microbes acting as crucial gatekeepers to human health, and provide new insight into muscle mass maintenance with respect to ageing,” said Pettersson.
“They lay the foundation for future studies that evaluate how microbes and their metabolites may be potential targets of intervention to improve skeletal muscle strength in the elderly, especially in countries such as Singapore with rapidly ageing populations."
Microbe-muscle links
Through a series of strength and movement-related exercises conducted on mice, Pettersson and colleagues found that mice with gut microbes had stronger skeletal muscles that can produce more energy when compared to mice without any gut microbes, known as germ-free mice.
Evidence for a link between gut microbes and skeletal muscle mass was strengthened when the international research team - from Singapore, Sweden, Switzerland, France, UK, US, and Australia – transplanted gut microbes from standard laboratory mice into germ-free mice.
Muscle growth and function in the germ-free mice were partially restored following the transplant.
The study also shed light on the possible link between gut microbes and communication between nerves and muscles, with teams reporting that germ-free mice had reduced levels of key proteins essential for the assembly and function of a neuromuscular junction - a chemical structure that allows a motor nerve cell to communicate with a skeletal muscle fibre.
These junctions allow signals to be transmitted to the muscle fibre, causing muscle contraction.
Transplanting gut microbes into germ-free mice partially restored the expression of these key proteins to the level observed in mice with gut bacteria, they added.
"While additional experiments are needed to fully obtain the mechanisms underlying muscle atrophy and dysfunction in the nerve-muscle junction in germ-free mice, the results presented here allow for important and interesting future studies relevant to muscle development, growth and formation of functional nerve-muscle communication,” Pettersson said.
Study details
Pettersson and his team conducted three sets of exercise tests on both mice with gut microbes and germ-free mice. In the weights test, each mouse was made to grasp a 26g weight to see if it could hold the weight for three seconds. Those who did so successfully then progressed to the next five weights, ranging from 33g to 100g.
The researchers also monitored the mice's movements for an hour in an open environment to measure the total distance they covered and the amount of time the mice spent standing on their hind legs.
Mice also ran on a treadmill set at a gradually increasing speed from 0 to 15 metres per minute, and then maintained at a constant speed.
Upon examination, the team found that on top of reduced skeletal muscle mass and increased expression of genes linked to muscle atrophy, skeletal muscles in germ-free mice also displayed problems with function and the generation of new mitochondria, whose role is to break down nutrients to form energy for cellular activity.
But when the researchers transplanted gut microbes from mice to germ-free mice, they found that these mice had their muscle growth and function partially restored, and showed reduced signs of muscle atrophy.
"This line of research will lead to novel ways to maintain or improve muscle mass, strength, and function by modulating the microbial composition in the gut,” said Pettersson. “Such strategies are expected to have broad applications in tackling muscle-related health issues.”
“One area with enormous potential is to delay or reverse age-related sarcopenia."
Source: Science Translational Medicine
Vol. 11, Issue 502, doi: 10.1126/scitranslmed.aan5662
“The gut microbiota influences skeletal muscle mass and function in mice”
Authors: Shawon Lahiri, et al