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Review
. 2022 Nov 4;14(21):4660.
doi: 10.3390/nu14214660.

Novel Therapeutic Approaches for Mitigating Complications in Short Bowel Syndrome

Jeffery Bettag  1 , Loren Po  1 , Cassius Cunningham  1 , Rahul Tallam  1 , Kento Kurashima  1 , Aakash Nagarapu  1 , Chelsea Hutchinson  2 , Sylvia Morfin  1 , Mustafa Nazzal  2 , Chien-Jung Lin  1 , Amit Mathur  1 , Rajeev Aurora  1 , Ajay K Jain  1
Affiliations
Review

Novel Therapeutic Approaches for Mitigating Complications in Short Bowel Syndrome

Jeffery Bettag et al. Nutrients. .

Abstract

Short bowel syndrome (SBS) is a particularly serious condition in which the small intestine does not absorb sufficient nutrients for biological needs, resulting in severe illness and potentially death if not treated. Given the important role of the gut in many signaling cascades throughout the body, SBS results in disruption of many pathways and imbalances in various hormones. Due to the inability to meet sufficient nutritional needs, an intravenous form of nutrition, total parental nutrition (TPN), is administered. However, TPN presents difficulties such as severe liver injury and altered signaling secondary to the continued lack of luminal contents. This manuscript aims to summarize relevant studies into the systemic effects of TPN on systems such as the gut-brain, gut-lung, and gut-liver axis, as well as present novel therapeutics currently under use or investigation as mitigation strategies for TPN induced injury.

Keywords: FGF19; FXR; GLP; Omega 3; gut brain axis; gut-liver axis; lipids; parenteral nutrition; short bowel syndrome.

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Conflict of interest statement

Ajay K. Jain is a consultant for Mirum Pharmaceuticals. The remaining authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Total Parenteral nutrition Associated injury. (A) During regular enteral nutrition, luminal bile acids activate gut farnesoid X receptor (FXR), releasing fibroblast growth factor 19 (FGF19). (B) FGF19 regulates hepatic cholesterol 7α-hydroxylase (CYP7A1), fat, and glucose metabolism. (C) Gut TGR5 activation by bile acids releases glucagon-like peptide-1 (GLP-1) and GLP-2. (D) GLP-1 modulates hepatic steatosis, insulin, and glucose; GLP-2 modulates gut growth. (E) Gut microbes deconjugate primary bile acids (FXR agonists) to secondary bile acids (TGR5 agonists). (F) Gut microbes also regulate cytokines, interleukins (ILs), and tumor necrosis factor-α (TNF-α), modulating liver and gut injury. FGFR4, FGF receptor 4. “Reproduced with permission from American Society for Parenteral and Enteral Nutrition, Nutrition in clinical practice; published by SAGE Publications, Inc., 2020”.
Figure 2
Figure 2
Generalized diagram of effects of TPN on various gut-organ axes.
See this image and copyright information in PMC

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