Gastroenteral investigators from the Johns Hopkins Children’s Center state that they have pinpointed a gene involving the mineral zinc in mice that they envision may induce zinc-based supplement to medically treat SBS patients.
In both children and adult sufferers of the condition, these findings published in Nature Communications marks a step toward better potential treatment regimens. Celiac sprue, which occurs in 10,000–20,000 US adults and children, is characterized by the injury and the small bowel contraction.
They recommended that children with SBS have poor intestinal function, the children often experience weight loss and require parenteral nutrition and other therapies and treatments, and they are prone to complications such as malnutrition, dehydration, unintentional weight loss, and even death.
Rehabilitative measures such as feeding regimens, medications, operative interventions and, at times, small bowel transplants are only partially curative and are associated with unwanted consequences such as infection and protracted hospital stay.
For their first study, the investigators employed a mouse model of SBS in the hope that SBS as seen in these mice might mirror SBS as seen in man. The researchers looked to see what a bypass near the colon looks like over time and they witnessed that a lot of the small intestinal villi—These are small, fine, fingerlike projections in the ‘small intestine’ into which the nutrients you eat are absorbed—started to grow and become longer naturally.
Hackam added: “The villi were adapting—you could say that they were reaching out for more food.” However, from the above analysis, it can be seen that these villi could not “catch up” or heal according to Hackam.
The researchers then used single cell RNA sequencing to quantify how much of the specific genes are being turned on. It allowed them to define up to ten gene-signalling routes in the model’s intestines and see which genes influenced healing, according to Hackam.
Analysing the zinc transporter gene expression employing quantitative polymerase chain reaction (q PCR)(a gene level estimate that uses quantitative measurement of RNA) it was observed that the levels of these zinc transporter genes in the intestines of these experimental models were 4 or 5 folds greater than in the control subjects.
First week group of mouse who was fed with liquid diet containing low zinc (13.5mg/kg/day zinc acetate) has less weight loss than those received extra zinc (13.38 ± 1.11% of body weight loss while 7.1 ± 1.19% of body weight loss in latter group).
In particular, high-zinc diet was more effective in increasing the odds of survival in rats and improving the absorptive surface area as well as absorptive capacity of the intestine due to longer, healthier-length intestinal villi.
Overall, we found that zinc supplement enhanced the capability of the mice to achieve enhanced recovery and improve their chances of survival,” said Maame Sampah, a research fellow and surgical trainee at Johns Hopkins Children’s Centre where she is conducting research under the supervision of Dr. Hackam and co-author of the research study.
To validate these findings in human biopsy samples, researchers investigated endoscopic or surgical tissue samples from 26 subjects (including 14 with SBS) acquired from Washington University in St Louis between 2008 to 2020.
Hackam adds that the conclusion of the study opens up a lot of hope to patients and their families who are living with SBS. They comprise potential new treatment regimens, wait or further development may reveal them to be safe and or effective.
Reference:
Maame Efua S. Sampah, Moore H, Ahmad R, Johannes Duess, Lu P, Lopez C, et al. Xenotransplanted human organoids identify transepithelial zinc transport as a key mediator of intestinal adaptation. Nature Communication
