BACKGROUND/OBJECTIVES: Indole-3-propionic acid (IPA) is a tryptophan-derived microbial metabolite that has been associated with protective effects against inflammatory and metabolic diseases. However, there is a lack of knowledge regarding the effects of IPA under physiological conditions and at the intestinal level.MATERIALS/METHODS: Human intestinal epithelial Caco-2 cells were treated for 2, 24, and/ or 72 h with IPA or its precursors – indole, tryptophan, and propionate – at 1, 10, 100, 250, or 500 μM to assess cell viability, integrity, differentiation, and proliferation. RESULTS: IPA induced cell proliferation and this effect was associated with a higher expression of extracellular signal-regulated kinase 2 (ERK2) and a lower expression of c-Jun. Although indole and propionate also induced cell proliferation, this involved ERK2 and c-Jun independent mechanisms. On the other hand, both tryptophan and propionate increased cell integrity and reduced the expression of claudin-1, whereas propionate decreased cell differentiation. CONCLUSIONS In conclusion, these findings suggested that IPA and its precursors distinctly contribute to the proliferation, differentiation, and barrier function properties of human intestinal epithelial cells. Moreover, the pro-proliferative effect of IPA in intestinal epithelial cells was not explained by its precursors and is rather related to its whole chemical structure.Maintaining IPA at physiological levels, e.g., through IPA-producing commensal bacteria, may be important to preserve the integrity of the intestinal barrier and play an integral role in maintaining metabolic homeostasis.

BACKGROUND: Lung cancer (LC) is the leading cause of cancer death. Patients treated with chemotherapy are at risk of developing chemotherapy-induced febrile neutropenia (FN), a potentially life-threatening complication. The aims of this study were (1) to characterize FN admissions of patients with LC in a pulmonology department, and (2) to determine associations between patient profiles, first-line antibiotic failure (FLAF) and mortality. METHODS: Retrospective observational case-series, based on the analysis of medical records of LC patients that required hospitalization due to chemotherapy-induced FN. RESULTS: A total of 42 cases of FN were revised, corresponding to 36 patients, of which 86.1% were male, with a mean age of 66.71±9.83 years. Most patients had a performance status (PS) equal or less than 1, and metastatic disease was present in 40.5% (n=17). Respiratory tract infections accounted for 42.9% (n=18) of FN cases, and multidrug-resistant Staphylococcus aureus was the most isolated agent. The mortality rate was 16.7% (n=7), and the FLAF was 26.2% (n=11). Mortality was associated with a PS≥2 (P=0.011), infection by a Gram-negative agent (P=0.001) and severe anemia (P=0.048). FLAF was associated with longer hospitalizations (P=0.020), PS≥2 (P=0.049), respiratory infections (P=0.024), and infection by a Gram-negative (P=0.003) or multidrug-resistant agent (P=0.014). CONCLUSIONS Lower PS, severe anemia, and infections by Gram-negative or multi-resistant agents seem to be associated with worse outcomes in FN patients.
Aged ; Anti-Bacterial Agents/adverse effects* ; Female ; Hospitalization ; Humans ; Lung Neoplasms/drug therapy* ; Male ; Methicillin-Resistant Staphylococcus aureus ; Middle Aged ; Retrospective Studies