• Transferring gut bacteria from young to old mice rejuvenates immune cells and increases mucus-secreting intestinal cells, important for protecting the intestinal wall. 
  • The Lachnospiraceae family of bacteria prevalent in young mice reduce gut leakage in old mice. 
  • The gut bacterial metabolite indole-3-carbinol (I3C) rejuvenates blood stem cells and reduces inflammation.

Our stem cells are important for regenerating damaged tissues, yet they lose this regenerative capacity with aging, exacerbating the deterioration of our organs. When it comes to blood (hematopoietic) stem cells — which give rise to all blood and immune cells — aging can lead to an increased risk of cardiovascular disease and blood-related cancers like leukemia. Now, researchers from Zhejiang University in China have begun to unravel the relationship between blood stem cells and gut bacteria during aging. 

Zeng and colleagues report in Blood that gut bacteria transfer from young mice rejuvenates aged blood stem cells and suppresses inflammation. “Young” gut bacteria also improve intestinal health by increasing mucus-secreting goblet cells and fortifying intestinal wall integrity. Furthermore, the China-based researchers pinpoint tryptophan and I3C as some of the metabolites responsible for the effects of young gut bacteria. 

Gut Bacteria Secretions Rejuvenate Old Blood  

Hematopoietic “blood” stem cells are the precursors to all blood cells, including red blood cells and white blood cells (immune cells). With age, blood stem cells lose their ability to generate new cells, leading to aberrant immune cell levels and inflammation. However, Zeng and colleagues found that feeding old mice gut bacteria from young mice restored the capacity of blood stem cells to generate new cells, improved immune cell levels, and suppressed inflammation. 

Furthermore, gut bacteria from young mice increased the number of goblet cells, which lubricate and protect the intestinal wall, in old mice. The young mouse bacteria also improved the integrity of the intestinal barrier, which is beneficial because dysfunction of the intestinal barrier can increase inflammation and affect cancer growth. Thus, the results demonstrate that transferring gut bacteria from young to old mice reduces inflammation and improves intestinal health by rejuvenating blood stem cells. 

(Zeng et al., 2023 | Blood) “Young” Gut Bacteria Increase Intestinal Mucus-Secreting Cells. Left: Representative images of the intestinal wall from aged mice fed gut bacteria from aged mice (FMT-AA), as a control group, and aged mice fed gut bacteria from young mice (FMT-YA) with arrows pointing at mucus-secreting goblet cells. Right: Graph showing an increase in goblet cells in FMT-YA mice compared to FMT-AA mice.

To explore which bacteria are responsible for rejuvenating blood stem cells, Zeng and colleagues fed Lachnospiraceae, a bacteria family found in high levels in young mice, to old mice. Mice fed Lachnospiraceae displayed rejuvenated blood stem cells and immune cell ratios, similar to full gut bacteria transfer. Also similar, Lachnospiraceae enhanced intestinal barrier integrity, suggesting that Lachnospiraceae is one of the main bacterial families responsible for the intestinal health benefits of young-to-old gut bacteria transfer. 

(Zeng et al., 2023 | Blood) The Gut Bacteria Family Lachnospiraceae Improves Intestinal Wall Integrity. Compared to mice given only salt water (PBS), mice fed Lachnospiraceae have reduced gut leakage (Plasma FITC-dextran), demonstrating improved gut barrier integrity.

The metabolites secreted by our gut bacteria can play a vital role in modulating the inflammatory status of distant organs via the bloodstream. By analyzing the gut bacteria metabolites of young mice, Zeng and colleagues found that the amino acid tryptophan and tryptophan metabolites, including indole-3-carbinol (I3C) were elevated. It was then found that tryptophan and I3C rejuvenated blood stem cells, enhanced immune cell numbers, and reduced inflammatory markers, with I3C having stronger effects.

(Zeng et al., 2023 | Blood) Indole-3-carbinol (I3C) Rejuvenates Stem Cells and Reduces Inflammation. Compared to no treatment (Control) and mice fed tryptophan (Tryptophan), mice fed the tryptophan metabolite I3C have more blood stem cells (LT-HSC count) and reduced inflammatory markers, including BM IL-1β.

Zeng and colleagues have helped unravel the complex relationship between gut bacteria (microbiota), the immune system, and age-related disease. A phenomenon called clonal hematopoiesis, whereby genetic mutations in blood stem cells are passed on to immune cells is highly prevalent in the elderly and associated with an increased risk of death, cancer, and heart attack. This phenomenon could possibly be prevented by rejuvenating blood stem cells with “young” gut bacteria.

“Our study… indicates that manipulating the gut ecosystem may be a promising strategy to rejuvenate aged [blood stem cells]. Still, we believe that this warrants future investigation to elucidate the relationship between gut microbiota and the development of clonal hematopoiesis on humans.” 

Supplementing with I3C?

The findings of Zeng and colleagues suggest that the age-reversing benefits of young bacteria are at least partly due to tryptophan and its metabolites, particularly I3C. High levels of tryptophan can be found in protein-rich foods like turkey, soybeans, and milk. Tryptophan and I3C can also be found in supplement form. However, whether dietary intake of tryptophan, or supplementing with I3C can mimic the effects of gut bacteria transfer is unknown. 

Still, there may be other anti-aging benefits to changing the composition of our gut bacteria, such as rejuvenation of muscle and skin, not mediated by I3C. For this reason, it may be more beneficial to improve our gut bacteria by making better dietary choices, such as increasing fiber intake or even supplementing with probiotics. With time, more studies may reveal the secrets to improving our gut microbiome the most efficiently.