ABSTRACT
Intestinal stem cells (ISCs) play a pivotal role in gut physiology by governing intestinal epithelium renewal through the precise regulation of proliferation and differentiation. The gut microbiota interacts closely with the epithelium through myriad of actions, including immune and metabolic interactions, which translate into tight connections between microbial activity and ISC function. Given the diverse functions of the gut microbiota in affecting the metabolism of macronutrients and micronutrients, dietary nutrients exert pronounced effects on host-microbiota interactions and, consequently, the ISC fate. Therefore, understanding the intricate host-microbiota interaction in regulating ISC homeostasis is imperative for improving gut health. Here, we review recent advances in understanding host-microbiota immune and metabolic interactions that shape ISC function, such as the role of pattern-recognition receptors and microbial metabolites, including lactate and indole metabolites. Additionally, the diverse regulatory effects of the microbiota on dietary nutrients, including proteins, carbohydrates, vitamins, and minerals (e.g. iron and zinc), are thoroughly explored in relation to their impact on ISCs. Thus, we highlight the multifaceted mechanisms governing host–microbiota interactions in ISC homeostasis. Insights gained from this review provide strategies for the development of dietary or microbiota-based interventions to foster gut health.
List of abbreviations
ACC1 | = | Acetyl-CoA-carboxylase |
AHR | = | Aryl hydrocarbon receptor |
APC | = | Adenomatous polyposis coli |
BAs | = | Bile acids |
BMPs | = | Bone morphogenetic proteins |
BSH | = | Bile salt hydrolase |
CBCs | = | Crypt-base columnar cells |
CSL | = | CBF-1/RBP-Jκ, Su(H), Lag-1 |
DCA | = | Deoxycholic acid |
Dkk1 | = | Dickkopf-related protein 1 |
DON | = | Deoxynivalenol |
ECs | = | Enterocytes |
EEs | = | Enteroendocrine cells |
EGF | = | Epidermal growth factor |
EGFR | = | Epidermal growth factor receptor |
ERK1/2 | = | Extracellular regulated kinase 1/2 |
FXR | = | Farnesoid X receptor |
GCPRs | = | G protein-coupled receptors |
HADCs | = | Histone deacetylases |
HCOs | = | Human colonic organoids |
HES | = | Hairy and Enhancer of split |
HFD | = | High-fat diet |
HIF-1α | = | Hypoxia-inducible factor-1α |
HIOs | = | HPSC-derived small intestinal organoids |
HMO | = | Human milk oligosaccharides |
HPSC | = | Human pluripotent stem cell |
ILC3 | = | innate lymphoid cells type 3 |
ISCs | = | Intestinal stem cells |
LCA | = | Lithocholic acid |
LGR5 | = | Leucine-rich repeat-containing G-protein-coupled receptor 5 |
LPS | = | lipopolysaccharide |
LTA | = | Lipoteichoic acid |
M3R | = | muscarinic 3 receptor |
MAMPs | = | Microorganism-associated molecular patterns |
MDP | = | Muramyl dipeptide |
MHE | = | Mid-hindgut endoderm |
NF-κB | = | Nuclear factor κB |
NICD | = | Notch intracellular domain |
NLRs | = | Nucleotide-binding oligomerization domain (NOD)-like receptors |
PG | = | peptidoglycan |
PGE2 | = | Prostaglandin E2 |
PPARα | = | Peroxisome proliferator-activated receptor alpha |
PPARδ | = | Peroxisome proliferator-activated receptor delta |
PRRs | = | Pattern recognition receptors |
rISCs | = | Reserve intestinal stem cells |
RNF43 | = | Ring finger protein 43 |
ROS | = | Reactive oxygen species |
SBAs | = | Secondary bile acids |
Se-Met | = | Selenomethionine |
SFCAs | = | Short-chain fatty acids |
TCFs | = | T-cell factors |
TGFα | = | Transforming growth factor-a |
TGR5 | = | Takeda G protein-coupled receptor 5 |
TLR2 | = | Toll-like receptor 2 |
TLR4 | = | Toll-like receptor 4 |
TLRs | = | Toll-like receptors |
Trp | = | Tryptophan |
YAP | = | Yes-associated protein |
ZNRF3 | = | ZNRF3 |
Acknowledgments
We extend our sincere admiration to the researchers in this field and within our laboratories for their unwavering dedication and hard work. We regret that we could not include citations of all the valuable works of scientists in this field owing to space constraints.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
WZ conceived and designed this review, edited the manuscript, and secured funding for the study. HW wrote the manuscript draft. CM participated in the concept development, edited and revised the manuscript. LX helped collect literature and draw the diagram. KY provided advice on the review structure. LS edited and proofread the manuscript. All authors contributed to the article and approved the final version of this manuscript.
Data Availability statement
Data sharing is not applicable to this article, as no datasets were generated or analyzed in the current study. were created using Figdraw software (www.figdraw.com).