Inflammatory bowel disease is associated with increased gut‐to‐blood penetration of short‐chain fatty acids: A new, non‐invasive marker of a functional intestinal lesion

Abstract

New Findings What is the central question of this study?‘Leaky gut’ has been found in intestinal and extra‐intestinal diseases. However, functional evaluation of intestinal permeability is not widely used as a diagnostic marker, possibly owing to significant limitations of currently used permeability assays. There is an unmet need for development of a new, non‐invasive test to assess intestinal function. What is the main finding and its importance?We show that an increased blood‐to‐stool ratio of the concentration of gut bacteria‐produced short‐chain fatty acids may be used as a marker of gut permeability. Our findings lay the groundwork for establishing a new, non‐invasive, risk‐free diagnostic tool in diseases associated with intestinal barrier malfunction, such as inflammatory bowel disease. Abstract Intestinal diseases, such as inflammatory bowel disease (IBD), are characterized by an impaired gut–blood barrier commonly referred to as ‘leaky gut’. Therefore, functional evaluation of the gut–blood barrier is a promising diagnostic marker. We hypothesized that short‐chain fatty acids (SCFAs) produced by gut bacteria might serve as a marker in IBD. Animal experiments were performed on male Sprague–Dawley rats with acetic acid‐induced colitis and in sham control animals. The gut–blood barrier permeability was determined by assessing the ratios of the following: (i) portal blood concentration of SCFAs (Cp) to faecal concentration of SCFAs (Cf); (ii) systemic blood concentration of SCFAs (Cs) to faecal concentration of SCFAs (Cf); and (iii) Cp and Cs of fluorescein isothiocyanate (FITC)–dextran administered into the colon. As a clinical study, we evaluated Cs, Cf and the Cs/Cf ratio of SCFAs in six paediatric patients with IBD, assessed as mild/moderate/severe by the Paediatric Ulcerative Colitis Activity Index (PUCAI) and the Paediatric Crohn's Disease Activity Index (PCDAI) at the time of sample collection, and nine age‐matched healthy control subjects. Rats with histologically confirmed IBD had significantly increased ratios of Cp/Cf and Cs/Cf for SCFAs. This was positively correlated with the plasma FITC–dextran concentration. Likewise, IBD patients showed a significantly higher Cs/Cf ratio for SCFAs, including acetic, valeric, isocaproic, caproic and propionic acids, in comparison to control subjects. In conclusion, in the rats and in paediatric patients with IBD we found an increased blood‐to‐stool ratio of SCFAs, suggesting an increased gut‐to‐blood penetration of SCFAs. These findings pave the way for a new, non‐invasive diagnostic tool in IBD and other diseases accompanied by intestinal barrier malfunction.

Alterations in fecal short chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) in men with benign prostatic hyperplasia (BPH) and metabolic syndrome (MetS)

“…Many studies have confirmed that SCFAs are involved in the pathophysiology of IBD and may be a prognostic marker of the disease state [ 76 ]. Jaworska et al [ 76 ] demonstrated that compared with healthy individuals, the ratio of acids in serum to acids in feces (acetate, valerate, isocaproic, caproic and propionic acids) is statistically significantly higher in patients with IBD. These data indicate that SCFAs may be involved in the disturbance of the intestinal barrier function [ 76 ].…”

“…Jaworska et al [ 76 ] demonstrated that compared with healthy individuals, the ratio of acids in serum to acids in feces (acetate, valerate, isocaproic, caproic and propionic acids) is statistically significantly higher in patients with IBD. These data indicate that SCFAs may be involved in the disturbance of the intestinal barrier function [ 76 ]. The research by Huda-Jaujan et al [ 38 ] also confirmed the role of SCFAs in the pathogenesis of IBD.…”

Plasma Short-Chain Fatty Acids and Their Derivatives in Women with Gestational Diabetes Mellitus

“…A study by Jaworska et al [58] showed that the amount of SCFA in plasma is due not only to how much the bacteria produce, but also to intestinal permeability. Its increase can be a symptom of intestinal malfunction, which is characteristic not only of diabetes mellitus, obesity and hypertension, but also of IBD.…”

Heart Failure Disturbs Gut–Blood Barrier and Increases Plasma Trimethylamine, a Toxic Bacterial Metabolite

“…This notion is based on the following findings: First, the SHHF had the same concentration of TMA in the colon content (which excludes differences in bacterial production of TMA) but a significantly higher level of TMA in the plasma. Hence, in comparison to WKY, SHHF showed a significantly higher blood-to-stool ratio of the bacterial metabolite concentration, a marker of gut–blood barrier permeability [ 15 ]. Second, the SHHF showed significant structural and functional disturbances in the intestinal wall in the form of reduced intestinal blood flow, decreased thickness of the colonic mucosa and disturbances in tight junction (TJ) proteins.…”

“…Therefore, in the present study, to establish the permeability of the gut to TMA in the present study, we used an indirect method; i.e., we calculated a systemic blood-to-stool ratio of the concentration of TMA. The latter method was previously validated in our lab for other gut microbiota products [ 15 ].…”