Gut microbiome is “paramount” to regenerative medicine, stress Japanese researchers

09 May 2022 --- As gut health continues to remain at the center of overall health, researchers at GN Corp Japan have discovered the gut microbiome to be crucial for regenerative medicine, with potential to combat neurological diseases.

“Management of the gut microbiome should be prominent in the RM process as it prepares the system to harness the full potential of sophisticated RM tools,” states GN Corp Japan, a cell culture therapy research corporation.

Traditionally RM involves tools that include cells (stem cells, progenitors, mature adult cells), cell-derived factors (cytokines) and scaffolds (extracellular matrices for cell engraftment).

“However, a standard RM approach may have limited success in combating neurological diseases unless the aggregations are searched,” the Japanese researchers explain.

The scientists have discovered new means of RM by involving GM, which influences all RM tools both directly and indirectly. The new RM method promotes the paracrine effect by stimulating the damaged cells to regenerate. 

Enhancing the microglia – glial cells derived from mesoderm that function as scavengers in the central nervous system – through GM resumes homeostasis in the brain. 

Notably, biological response modifier glucans control GM, preventing aggregation and the spread of abnormal proteins to the brain. As a result, the donor cells do not have to persist to ensure a disease-free status.

Healthy adults have more than 1,000 species of bacteria.The second genome
The gut microbiome represents a group of cells that plays a role in cell differentiation, proliferation and paracrine effects and influences tissue repair and regeneration. GM even affects organs at a distant site through its inter-organ axes, such as the gut-brain axis. Thus, it can affect different treatment outcomes.

A study by the European Metagenomics of the Human Intestinal Tract (MetaHIT) and the NIH-funded Human Microbiome Project (HMP) assessed the gut metagenomes of 1,070 individuals. They found that the human gut has 30 times more genes than the human genome. 

Genomes are all genetic information of an organism. Thus, because of the extent of its functionality, GM is viewed as the “second genome” of the body.

Healthy adults have more than 1,000 species of bacteria, with bacteroidetes and firmicutes being the dominant phyla. Gut microbes release short-chain fatty acids (SCFAs) from indigestible dietary fibers. 

The short-chain fatty acids are the energy source for intestinal mucosa, and they are vital for regulating both the immunity and tumorigenesis in the gut. 

Other than the short-chain fatty acids, the GM produces many other microbial products such as uremic toxins, bile acids, nitric oxide, vitamin K and vitamin B complex, to name but a few, as well as gut hormones and neurotransmitters which control metabolism and body function.

The importance of bio-synergies
The novel research into GM’s role in RM has found a synergy between the gut microbiome and mesenchymal stem cells (MSC)-based regeneration, especially in the case of inflammatory bowel disease (IBD). 

Gut bacterial secretions control the cytokine gene transcription and surface protein expressions in MSCs. They also improve the immunomodulation ability of bone marrow MSCs.

Meanwhile, some conditioning treatments such as hematopoietic stem cell transplantation, chemotherapy, radiotherapy, and immunosuppressive therapy can disrupt the gut microbiome. 

A few strategies to counter that are lactobacillus administration, probiotics, prebiotics and fecal microbiota transplantation.

Different bacteria, different diseases
A growing number of clinical insights show how GM is linked to different diseases. It has been recognized that balanced GM is essential to cardiac repair. 

Some metabolites and microorganisms have been linked to the development of coronary artery disease and atherosclerosis. 

A comparison between healthy adults and coronary patients revealed the presence of Helicobacter pylori, Cytomegalovirus, hepatitis C virus, Chlamydia pneumoniae and Porphyromonas gingivalis in the affected individuals.

Meanwhile, experimental studies on mice have demonstrated that a reduction in Lactobacillus caused myocardial infarction. Other clinical findings show that dietary short-chain fatty acid supplementation improved the mice’s health.

An imbalance in GM can also harm kidneys. Metabolites from an imbalanced gut consisting of urea, indoxyl sulfate and p-cresyl sulfate cause abnormal activation of immune cells, and overproduction of antibodies, immune complexes and inflammatory factors can damage the renal parenchyma, the functional part of the kidney.

The health of GM differs in patients based on the disease type. For example, such microbes as Escherichia coli, Klebsiella pneumoniae and Streptococcus viridans are claimed to be causing heart disease.

Beneficial probioticsManagement of the GM should be essential in the RM process as it prepares the system to harness the full potential of sophisticated RM tools.
The state of GM is also reflected in the quality of a person’s bone health. Experimental studies on mice demonstrated that a 99% decrease in gut microbe caused increased trabecular bone mass. While Lactobacillus reuteri probiotic treatment protected the mice from bone-mass loss.

The probiotic L. casei restores the SCFA-producing gut microbiome, vitamin B3 metabolism, lowers blood pressure, ameliorated kidney disease and prevented complications in chronic kidney disease patients.

Previously, a study by Health-Ade also found that prebiotics are more beneficial for the gut microbiome than probiotics. 

Probiotics and other strategies such as prebiotics, dietary interventions and lifestyle modifications effectively promote regeneration, claims the report. 

The gut microbiome works continuously, starting from repair, inflammation and tissue regeneration and it continues to be present even after tissue maturation for homeostasis, making GM management crucial for the success of any RM tool.

A previous US-based study identified 15 gut microbes that are prominent in diets rich in healthy and plant-based foods and may tackle illnesses such as heart disease, type 2 diabetes, and obesity.

Last year ADM predicted microbiome health awareness to be one of the leading global consumer trends.

Edited by Ilze Vitola