Critically ill patients are physiologically unstable and recent studies indicate that the intestinal microbiota could be involved in the health decline of such patients during ICU stays. This study aims to assess the intestinal microbiota in critically ill patients with and without sepsis and to determine its impact on outcome variables, such as medical complications, ICU stay time, and mortality. A multi-center study was conducted with a total of 250 peri-rectal swabs obtained from 155 patients upon admission and during ICU stays. Intestinal microbiota was assessed by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. Linear mixed models were used to integrate microbiota data with more than 40 clinical and demographic variables to detect covariates and minimize the effect of confounding factors. We found that the microbiota of ICU patients with sepsis has an increased abundance of microbes tightly associated with inflammation, such as Parabacteroides, Fusobacterium and Bilophila species. Female sex and aging would represent an increased risk for sepsis possibly because of some of their microbiota features. We also evidenced a remarkable loss of microbial diversity, during the ICU stay. Concomitantly, we detected that the abundance of pathogenic species, such as Enterococcus spp., was differentially increased in sepsis patients who died, indicating these species as potential biomarkers for monitoring during ICU stay. We concluded that particular intestinal microbiota signatures could predict sepsis development in ICU patients. We propose potential biomarkers for evaluation in the clinical management of ICU patients.

Objective: To determine the concentration of stool short-chain fatty acids (SCFAs) in critically ill patients with sepsis and to compare the results between the critically ill patient and the control group. Methods: This descriptive, multicenter, observational study was conducted in five health institutions. Over a 6-month study period, critically ill patients with sepsis who were admitted to the intensive care unit (ICU) and met the inclusion criteria were enrolled, and a control, paired by age and sex, was recruited for each patient. A spontaneous stool sample was collected from each participant and a gas chromatograph coupled to a mass spectrometer (Agilent 7890/MSD 5975 C) was used to measure the concentrations SCFAs. Results: The final sample included 44 patients and 45 controls. There were no differences in the age and sex distributions between the groups (p > 0.05). According to body mass index (BMI), undernutrition was more prevalent among critically ill patients, and BMI in control subjects was most frequently classified as overweight (p ¼ 0.024). Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were significantly lower in the critically ill patient group than in the control group (p ¼ 0.000). No association with outcome variables (complications, ICU stay, and discharge condition) was found in the patients, and patients diagnosed with infection on ICU admission showed significant decreases in butyric and isobutyric acid concentrations with respect to other diagnostic criteria (p < 0.05). Conclusions:The results confirm significantly lower concentrations of stool SCFAs in critically ill patients with sepsis than in control subjects. Due to its role in intestinal integrity, barrier function, and anti-inflammatory effect, maintaining the concentration of SCFAs may be important in the ICU care protocols of the critical patient.

Background Aging generates changes in the gut microbiota, affecting its functionality. Little is known about gut microbiota in critically ill older adults. The objective of this study was to describe the profile of gut microbiota in a cohort of critically ill older adults. Methods This observational study was conducted in five health institutions. Over a 6-month study period, critically ill patients over 18 years old who were admitted to the intensive care unit were enrolled. Fecal microbiota profiles were determined from 155 individuals, over 60 years old (n = 72) and under 60 years old (n = 83). Gut microbiota was analyzed by sequencing the V3-V4 region of the 16S rRNA gene. Alpha and beta diversity, operational taxonomic units and the interaction of gut microbiota with variables under study were analyzed. Amplicon sequence variants (ASVs) specifically associated with age were recovered by including gender, discharge condition, BMI, ICU stay and antibiotics as covariates in a linear mixed model. Results In older adults, sepsis, malnutrition, antibiotic prescription and severity (APACHE and SOFA scores) were higher than in the group under 60 years of age. Alpha diversity showed lower gut microbiota diversity in those over 60 years of age (p < 0.05); beta diversity evidenced significant differences between the groups (PERMANOVA = 1.19, p = 0.038). The microbiota of the adults under 60 years old showed greater abundance of Murdochiella, Megasphaera, Peptoniphilus and Ezakiella, whereas those over 60 years old Escherichia-Shigella and Hungatella were more abundant. Conclusion The gut microbial community was altered by different factors; however, age significantly explained the variability in critically ill patients. A lower presence of beneficial genera and a higher abundance of pathogens was observed in adults over 60 years old.

ResumenAntecedentes: diversos estudios han mostrado cambios en la microbiota intestinal (MI) y los áci-dos grasos de cadena corta (AGCC) en pacientes críticos con síndrome de respuesta inflamatoria sistémica (SRIS). Objetivo: revisar la evidencia sobre el papel de la MI y los AGCC en pacientes críticos y su modulación con prebióticos, probióticos y simbióticos. Materiales y métodos: búsque-da de artículos en bases de datos bibliográficas Pubmed, Science Direct, Ovid, Medline y Scopus, utilizando como descriptores microbiota, paciente crítico, unidad de cuidados intensivos, síndrome de respuesta inflamatoria sistémica, ácidos grasos de cadena corta, probióticos, prebióticos y simbióticos. Resultados: la MI en pacientes críticos está disminuida tanto en número de bacterias como en diversidad, lo cual puede resultar en una desregulación de la respuesta inmune sistémica ante la invasión de microorganismos patógenos. Los cambios en los AGCC en pacientes críticos se atribuyen a una disminución de bacterias anaerobias obligadas y sustratos de fermentación necesarios para su producción. La modulación de la MI con probióticos, prebióticos y simbióticos sugiere mejoría en la función intestinal. Conclusiones: la MI y los AGCC en pacientes críticos se encuentran alterados, de ahí que mantener el equilibrio en el entorno intestinal probablemente desempeñe una función clave para disminuir complicaciones y mejorar su pronóstico.Palabras clave: paciente crítico, microbiota, ácidos grasos de cadena corta, síndrome de respuesta inflamatoria sistémica, probióticos, prebióticos, simbióticos. Gut Microbiota and Short-Chain Fatty Acids in Critically Ill Patients AbstractBackground: Different studies have shown changes in gut microbiota and short-chain fatty acids in critically ill patients with Systemic Inflammatory Response Syndrome (SIRS). Aim: To review the evidence about the role of gut microbiota and SCFAs in critically patients and its modulation with prebiotics, probiotics and symbiotic. Materials and Methods: A search of the literature in Pubmed, Science Direct, Ovid, Medline and Scopus databases was conducted. The terms used were microbiota, critically ill, intensive care unit, systemic inflammatory response syndrome, short-chain fatty acids, prebiotics, probiotics and symbiotic. Results: The intestinal microbiota in critically ill patients is reduced in number and diversity, which can lead to dysregulation of the systemic immune response to the pathogenic invasion. Changes in SCFAs in critically ill patients are attributed to a decrease of obligate anaerobic bacteria and the fermentation substrates required for its production. The gut microbiota modulation with prebiotics, probiotics and symbiotic suggest improvement in bowel function. Conclusions: Gut microbiota and SCFAs are altered in critically ill patients; therefore, maintaining the intestinal environment is key for reducing complications and improving prognosis.

Adenaria floribunda is a native species found in tropical regions of South America used as a traditional medicine. Ultrasound-assisted extraction (UAE) is an extraction process known to increase the extraction yield, reduce extraction times, and use low temperatures. This study aims to obtain water-based extracts from A. floribunda stems using UAE, hot water extraction (HWE), and Soxhlet extraction and perform an economic analysis. The global extraction yield (GEY) and total phenolic compounds (TPC) of extracts ranged from 5.24% to 10.48% and from 1.9 ± 0.44 mg GAE g−1 DW to 6.38 ± 0.28 mg GAE g−1, respectively. Gallic acid, catechin, and ferulic acid were identified in the extract using HPLC-UV. Results indicate that Soxhlet extraction has the best performance regarding GEY and TPC. However, after performing an economic assessment, the cost of manufacturing (COM) of Soxhlet extraction (US$ 5.8 flask−1) was higher than the UAE (US$ 3.86 flask−1) and HWE (US$ 3.92 flask−1). The sensitivity results showed that obtaining extracts from A. floribunda by UAE and HWE is economically feasible when the selling price is above US$ 4 flask−1. Soxhlet extraction is a feasible technique when the selling price is above US$ 7 flask−1.