Septic acute kidney injury and gut microbiome: Should we change our approach? / Lesión renal aguda secundaria a sepsis y microbioma intestinal: ¿debemos modificar nuestro enfoque?

Incidence of acute kidney injury (AKI) remained relatively stable over the last decade and the adjusted risks for it and mortality are similar across different continents and regions. Also, the mortality of septic-AKI can reach 70% in critically-ill patients. These sole facts can give rise to a question: is there something we do not understand yet? Currently, there are no specific therapies for septic AKI and the treatment aims only to maintain the mean arterial pressure over 65mmHg by ensuring a good fluid resuscitation and by using vasopressors, along with antibiotics. On the other hand, there is an increased concern about the different hemodynamic changes in septic AKI versus other forms and the link between the gut microbiome and the severity of septic AKI. Fortunately, progress has been made in the form of administration of pre- and probiotics, short chain fatty acids (SCFA), especially acetate, and also broad-spectrum antibiotics or selective decontaminants of the digestive tract in a successful attempt to modulate the microbial flora and to decrease both the severity of AKI and mortality. In conclusion, septic-AKI is a severe form of kidney injury, with particular hemodynamic changes and with a strong link between the kidney and the gut microbiome. By modulating the immune response we could not only treat but also prevent severe forms. The most difficult part is to categorize patients and to better understand the key mechanisms of inflammation and cellular adaptation to the injury, as these mechanisms can serve in the future as target therapies.(AU)

La incidencia de la lesión renal aguda (LRA) se ha mantenido relativamente estable a lo largo de la última década, con unos riesgos ajustados de padecer y morir a consecuencia de esta enfermedad similares en los distintos continentes y regiones. La mortalidad asociada a la LRA secundaria a sepsis puede llegar a 70% en los pacientes que se encuentran en estado crítico. Estos hechos, por sí mismos, deben llevarnos a plantearnos la siguiente pregunta: ¿se nos escapa algo que aún no comprendemos? Actualmente no se dispone de terapias específicas para la LRA secundaria a sepsis y el tratamiento se centra únicamente en mantener la presión arterial media por encima de los 65mmHg mediante una rehidratación adecuada, vasopresores y antibióticos. Asimismo, cada vez existe mayor interés por las diferentes alteraciones hemodinámicas que se producen en comparación con otras formas de la enfermedad, así como por la relación existente entre el microbioma intestinal y la gravedad. Afortunadamente, se ha avanzado notablemente en la forma en la que se administran los prebióticos y los probióticos, los ácidos grasos de cadena corta (AGCC), especialmente el acetato, los antibióticos de amplio espectro o los detoxificantes selectivos del tracto digestivo, en un intento exitoso de modular la flora microbiana y disminuir tanto la gravedad de la LRA como su mortalidad. En conclusión, la LRA secundaria a sepsis es una forma grave de lesión renal que provoca unos cambios hemodinámicos específicos y en la que se observa una estrecha relación entre la función renal y el microbioma intestinal. La modulación de la respuesta inmunitaria no solo permitiría tratar esta enfermedad, sino también prevenir las formas graves de la misma. La parte más difícil de este enfoque radica en clasificar correctamente a los pacientes y comprender mejor los mecanismos clave de la inflamación y la adaptación celular a la lesión, ya que estos pueden convertirse en futuras dianas terapéuticas.(AU)

The urogenital microbiome in chronic kidney disease patients on peritoneal dialysis / El microbioma urogenital en pacientes con enfermedad renal crónica en diálisis peritoneal

Introduction and objectives: Diabetes, dyslipidemia, older age, gender, urinary tract infections, and recent antibiotic intake have been associated with a decrease in the urobiome richness and other fluctuations in this microbiome. Gut and blood microbiome have been reported to be altered in patients with chronic kidney disease (CKD), and specifically in peritoneal dialysis (PD) patients. Still, there are currently no studies describing the urogenital microbiome in CKD-PD patients. In this study we characterized the urobiome profile in 46 PD patients and analyzed its clinical and inflammatory parameters. Materials and methods: Mid-stream urine, fecal and blood samples were collected from 46 patients undergoing PD at Centro Hospitalar Universitário de São João (CHUSJ) in Porto, Portugal. Exclusion criteria were age under 18 years old, inability to give informed consent, history of infection in the last three months, and antibiotic intake in the last three months. The microbiome communities were analyzed by amplification and sequencing of the V3–V4 region of the bacterial 16S rRNA gene. Correlations with the patients’ clinical data and inflammatory profile were performed. Results: CKD-PD patients presented a unique urobiome profile dominated by Bacillota, Actinomycetota and Pseudomonadota and characterized by a lower Shannon diversity than fecal and blood microbiome. The taxonomic profiles of urogenital samples were organized in multiple subtypes dominated by populations of Lactobacillus, Staphylococcus, Streptococcus, Gardnerella, Prevotella, Escherichia-Shigella, being similar to other non-PD-CKD patients. Gender, sCD14, residual diuresis and history of peritonitis were significantly associated to variations in the urobiome. Although not reaching statistical significance, diabetes and the time on PD also showed association with particular taxonomic groups... (AU)

Introducción y objetivos: Diabetes, dislipemia, edad avanzada, género, infecciones del tracto urinario y toma reciente de antibióticos, entre otras, se han asociado a una disminución en la riqueza del urobioma y a otras fluctuaciones de dicho microbioma.Recientemente, se han descrito alteraciones en losmicrobiomas intestinal y en sangreen pacientes con enfermedad renal crónica (ERC) y, específicamente, en pacientes en diálisis peritoneal (DP).A pesar de ello, aún no existen estudios que describan el microbioma urogenital en pacientes en DP. En el presente trabajo, caracterizamos el urobioma en 46 pacientes en DP. Pacientes y métodos: Se recogieron muestras de orina (micción espontánea), heces y sangre de 46 pacientes en DP del Centro HospitalarUniversitário de São João en Oporto, Portugal. Los criterios de exclusión fueron edad menor a 18 años, incapacidad para entenderel consentimiento informado, e historia de infección y toma de antibióticos en los últimos 3 meses. Las comunidades microbiológicas fueron analizadas por amplificación y secuenciación de las regiones V3-V4 del 16S rRNA bacteriano. Se realizaron correlaciones con los datos clínicos y el perfil inflamatorio de los pacientes. Resultados: Los pacientes en DP presentaron un urobioma único dominado por Bacillota, Actinomycetota yPseudomonadota, y caracterizado por una menor diversidad de Shannon que los microbiomas en sangre e intestinal. Los perfiles taxonómicos de las muestras urogenitales se organizaron en múltiples subtipos dominados por poblaciones de Lactobacillus, Staphylococcus, Streptococcus, Gardnerella, Prevotella, Escherichia-Shigella, siendo similar al descrito para otros pacientes con ERC no en DP.Género, factor sCD14, diuresis residual yantecedentes de peritonitis se asociaron de forma significativa a cambios en el urobioma... (AU)

Clonal relationship, virulence genes, and antimicrobial resistance of Morganella morganii isolated from community-acquired infections and hospitalized patients: a neglected opportunistic pathogen

Morganella morganii is a bacterium belonging to the normal intestinal microbiota and the environment; however, in immunocompromised individuals, this bacterium can become an opportunistic pathogen, causing a series of diseases, both in hospitals and in the community, being urinary tract infections more prevalent. Therefore, the objective of this study was to evaluate the prevalence, virulence profile, and resistance to antimicrobials and the clonal relationship of isolates of urinary tract infections (UTI) caused by M. morganii, both in the hospital environment and in the community of the municipality of Londrina-PR, in southern Brazil, in order to better understand the mechanisms for the establishment of the disease caused by this bacterium. Our study showed that M. morganii presents a variety of virulence factors in the studied isolates. Hospital strains showed a higher prevalence for the virulence genes zapA, iutA, and fimH, while community strains showed a higher prevalence for the ireA and iutA genes. Hospital isolates showed greater resistance compared to community isolates, as well as a higher prevalence of multidrug-resistant (MDR) and extended-spectrum beta lactamase (ESBL)-producing isolates. Several M. morganii isolates from both sources showed high genetic similarity. The most prevalent plasmid incompatibility groups detected were FIB and I1, regardless of the isolation source. Thus, M. morganii isolates can accumulate virulence factors and antimicrobial resistance, making them a neglected opportunistic pathogen. (AU)

Gut microbiome resilience of green-lipped mussels, Perna canaliculus, to starvation

Host gut microbiomes play an important role in animal health and resilience to conditions, such as malnutrition and starvation. These host-microbiome relationships are poorly understood in the marine mussel Perna canaliculus, which experiences significant variations in food quantity and quality in coastal areas. Prolonged starvation may be a contributory factor towards incidences of mass mortalities in farmed mussel populations, resulting in highly variable production costs and unreliable market supplies. Here, we examine the gut microbiota of P. canaliculus in response to starvation and subsequent re-feeding using high-throughput amplicon sequencing of the 16S rRNA gene. Mussels showed no change in bacterial species richness when subjected to a 14-day starvation, followed by re-feeding/recovery. However, beta bacteria diversity revealed significant shifts (PERMANOVA p-value < 0.001) in community structure in the starvation group and no differences in the subsequent recovery group (compared to the control group) once they were re-fed, highlighting their recovery capability and resilience. Phylum-level community profiles revealed an elevation in dominance of Proteobacteria (ANCOM-BC p-value <0.001) and Bacteroidota (ANCOM-BC p-value = 0.04) and lower relative abundance of Cyanobacteria (ANCOM-BC p-value = 0.01) in the starvation group compared to control and recovery groups. The most abundant genus-level shifts revealed relative increases of the heterotroph Halioglobus (p-value < 0.05) and lowered abundances of the autotroph Synechococcus CC9902 in the starvation group. Furthermore, a SparCC correlation network identified co-occurrence of a cluster of genera with elevated relative abundance in the starved mussels that were positively correlated with Synechococcus CC9902... (AU)

Gut microbiota composition in pediatric populations with obesity: a systematic review / Composición de la microbiota intestinal en población pediátrica con obesidad: una revisión sistemática

The increasing prevalence of obesity among children and adolescent’s wide is a public health problem, resulting from the interaction of genetic, environmental and lifestyle factors. Obesity can lead to dysbiosis of the gut microbiota. This systematic review aims to gather scientific information available on the composition of gut microbiota in children/ adolescents with overweight/obesity. Research studies were identified through a scientific database (PubMed). The key words used were “Obese” OR “Overweight” AND “adolescent” OR “children” AND “microbiota”. Observational and intervention studies in children/adolescents having either overweight or obesity were included in this review, belonging to the last ten years – from December 2012 to October 2022. The initial search resulted in 409 references, 379 of them were excluded because the participants had major pathologies other than obesity or overweight. From the remaining articles, others were excluded due to not providing information on the number of participants, or not including data on microbiota composition. A total of 16 articles were selected: 12 observational studies and 4 intervention studies. Among the observational studies that compared overweight/obesity vs. normal weight or metabolically unhealthy obese vs. metabolically healthy obese children/adolescents, at least two studies found higher levels of Firmicutes, Proteobacteria, Bacteroidales, Adlercreutzia, Bifidobacterium, Escherichia coli, and Clostridium. Moreover, lower abundances of Bacteroidetes, Verrucomicrobia, Bacteroides, and Akkermansia were observed. Regarding intervention studies consisting of supplementation of oligofructose- enriched inulin and a weight reduction program, higher proportions of Actinobacteria were observed after the intervention. Clostridia was also found in higher abundances after interventions that used a combined strength and endurance training program and a weight reduction program. The findings suggest that obesity decreased microbiota diversity and increases species associated with inflammation. The results are consistent with previous studies in adults. This information will be useful for designing dietary interventions to prevent or reverse dysbiosis in individuals with obesity.(AU)

La creciente prevalencia de obesidad en niños y adolescentes es un problema de salud pública, resultado de la interacción de factores genéticos, ambientales y de estilo de vida. La obesidad puede provocar una disbiosis de la microbiota intestinal. Esta revisión sistemática tiene como objetivo recopilar información científica disponible sobre la composición de la microbiota intestinal en niños/adolescentes con sobrepeso/obesidad. Los estudios de investigación se identificaron a través de una base de datos científica (PubMed). Las palabras clave utilizadas fueron “obeso” O “Sobrepeso” Y “adolescente” O “niños” Y “microbiota”. En esta revisión se incluyeron estudios observacionales y de intervención en niños/adolescentes con sobrepeso u obesidad, pertenecientes a los últimos diez años, de diciembre de 2012 a octubre de 2022. La búsqueda inicial resultó en 409 referencias, de las cuales 379 fueron excluidas porque los participantes tenían patologías mayores además de la obesidad o el sobrepeso. De los artículos restantes, se excluyeron otros por no proporcionar información sobre el número de participantes o por no incluir datos sobre la composición de la microbiota. Se seleccionaron un total de 16 artículos: 12 estudios observacionales y 4 estudios de intervención. Entre los estudios observacionales que compararon el sobrepeso/obesidad frente al peso normal o los niños y adolescentes obesos metabólicamente no saludables frente a los obesos metabólicamente sanos, al menos dos estudios encontraron niveles más altos de Firmicutes, Proteobacterias, Bacteroidales, Adlercreutzia, Bifidobacterium, Escherichia coli y Clostridium. Además, se observaron menores abundancias de Bacteroidetes, Verrucomicrobia, Bacteroides y Akkermansia. En cuanto a los estudios de intervención consistentes en suplementación con inulina enriquecida con oligofructosa y un programa de reducción de peso, se observaron mayores proporciones de Actinobacteria después de la intervención. Los clostridios también se encontraron en mayor abundancia después de las intervenciones que utilizaron un programa combinado de entrenamiento de fuerza y resistencia y un programa de reducción de peso. Los hallazgos sugieren que la obesidad disminuye la diversidad de la microbiota y aumenta las especies asociadas con la inflamación. Los resultados son consistentes con estudios previos en adultos. Esta información será útil para diseñar intervenciones dietéticas que prevengan o reviertan la disbiosis en individuos con obesidad.(AU)

Effects of effective microorganisms on the physiological status, intestinal microbiome, and serum metabolites of Eriocheir sinensis / Efectos de microorganismos eficaces sobre el estado fisiológico, el microbioma intestinal y los metabolitos séricos de Eriocheir sinensis

The compound known as effective microorganisms (EMs) is widely used in aquaculture to improve water quality, but how they affect the health of Chinese mitten crab (Eriocheir sinensis) is unclear, especially in terms of intestinal microbiota and serum metabolites. In this study, we fed juvenile crabs with an EM-containing diet to explore the effects of EM on the physiological status, intestinal microbiome, and metabolites of E. sinensis. The activities of alanine aminotransferase and alkaline phosphatase were significantly enhanced by EM, indicating that EM supplementation effectively enhanced the antioxidant capacity of E. sinensis. Proteobacteria, Tenericutes, Firmicutes, Bacteroidetes, and Actinobacteria were the main intestinal microbes in both the control and EM groups. Linear discriminant effect size analysis showed that Fusobacteriaceae, Desulfovibrio, and Morganella were biomarkers in the control group, and Exiguobacterium and Rhodobacteraceae were biomarkers in the EM group. Metabolomics analysis revealed that EM supplementation increased cellular energy sources and decreased protein consumption, and oxidative stress. Together, these results indicate that EM can optimize the intestinal microbiome and serum metabolites, thereby benefiting the health of E. sinensis.(AU)

The effect of metformin combined with liraglutide on gut microbiota of Chinese patients with type 2 diabetes / El efecto de la metformina combinada con liraglutida sobre la microbiota intestinal de pacientes chinos con diabetes tipo 2

Background: Metformin (MET) is a first-line therapy for type-2 diabetes mellitus (T2DM). Liraglutide (LRG) is a glucagon-like peptide-1 receptor agonist used as a second-line therapy in combination with MET. Methods: We performed a longitudinal analysis comparing the gut microbiota of overweight and/or pre-diabetic participants (NCP group) with that of each following their progression to T2DM diagnosis (UNT group) using 16S ribosomal RNA gene sequencing of fecal bacteria samples. We also examined the effects of MET (MET group) and MET plus LRG (MET+LRG group) on the gut microbiota of these participants following 60 days of anti-diabetic drug therapy in two parallel treatment arms. Results: In the UNT group, the relative abundances of Paraprevotella (P = 0.002) and Megamonas (P = 0.029) were greater, and that of Lachnospira (P = 0.003) was lower, compared with the NCP group. In the MET group, the relative abundance of Bacteroides (P = 0.039) was greater, and those of Paraprevotella (P = 0.018), Blautia (P = 0.001), and Faecalibacterium (P = 0.005) were lower, compared with the UNT group. In the MET+LRG group, the relative abundances of Blautia (P = 0.005) and Dialister (P = 0.045) were significantly lower than in the UNT group. The relative abundance of Megasphaera in the MET group was significantly greater than in the MET+LRG group (P = 0.041). Conclusions: Treatment with MET and MET+LRG results in significant alterations in gut microbiota, compared with the profiles of patients at the time of T2DM diagnosis. These alterations differed significantly between the MET and MET+LRG groups, which suggests that LRG exerted an additive effect on the composition of gut microbiota.(AU)

A Study of the Relationship between Inflammatory Immune Function and Intestinal Flora in Adolescent Patients with First-Episode Depression

Background: Depression has become one of the most common mood disorders in adolescents, with an increasing incidence each year. Abnormal activation of peripheral immunity causes an increase in pro-inflammatory factors, which in turn affects neuroendocrine dysfunction and alters neurobiochemistry, leading to depression. In this study, we aimed to explore the relationship between inflammatory immune function and intestinal flora in adolescents with first-episode depression. Methods: A total of 170 cases of adolescent patients with first-episode depression who attended our hospital from January 2020 to March 2023 were retrospectively selected as the observation group. Simultaneously, 170 individuals who underwent a healthy physical examination during the same period were chosen as the control group. The enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of monoamine neurotransmitters 5-hydroxytryptamine (5-HT), substance P (SP), neuropeptide Y (NPY), serum tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 in the patients. Flow cytometry was utilized to assess the levels of T-lymphocytes CD3+, CD4+, and CD8+ cells. The levels of 16S ribosomal RNA (16SrRNA) method were used to determine the intestinal flora of the subjects in both groups. Inflammatory factor levels, immune function, and intestinal flora expression were observed, and correlation analysis was performed. Results: The levels of 5-HT and NPY in the observation group were lower than those in the control group. The SP level was significantly higher in the observation group compared to the control group (p < 0.05). The observation group demonstrated significantly higher TNF-α, IL-1β, and IL-6 levels than the control group (p < 0.05). The values of CD3+, CD4+, CD4+/CD8+ in the observation group were lower than those in the control group (p < 0.05), whereas the CD8+ values were notably higher (p < 0.05). ... (AU)

The significance of appendectomy in the context of colorectal cancer: impacts on gut microbiota and beyond

Colorectal cancer (CRC) remains one of the most common malignancies globally, of which the initiative factors are multiple and complex. More recently, the major roles played by gut microbiota in the carcinogenesis of CRC have been uncovered, which indicates that dysbiosis caused by specific bacterial or fungal species may contribute to the malignant progression of CRC. Meanwhile, appendix, classically identified as an evolutionary relict with negligible physiological functions, has been found to play crucial roles in the immune modulation process and microbiome composition of gut by its lymphoid tissue features. In addition, appendectomy, a common surgical operation modality, has also been found to be closely correlated with the clinical outcomes of multiple diseases, including CRC. Naturally, these evidence collectively point to a possibility that the appendectomy may influence the pathological process of CRC through its impacts on gut microbiome. (AU)

Abundancia de Akkermansia muciniphila según el IMC en pacientes con trastornos gastrointestinales: estudio piloto de cohorte transversal / Akkermansia muciniphila abundance according to BMI in patients with GI disorders: cross-sectional cohort pilot study

En los últimos años, Akkermansia muciniphila ha ganado prominencia en la investigación científica debido a su posible contribución a la regulación de la respuesta inmunológica, la sensibilidad a la insulina, la prevención de enfermedades inflamatorias y la salud metabólica. En concreto, su abundancia se ha correlacionado inversamente con el peso corporal y su presencia podría tener un efecto beneficioso en la regulación del metabolismo. El objetivo del presente estudio fue examinar si A. muciniphila estaba asociada con el IMC en personas con trastornos gastrointestinales. Los resultados sugieren que la abundancia de A. muciniphila es muy baja en pacientes con trastornos gastrointestinales (1,35%) y menor en personas con sobrepeso u obesidad, aunque los resultados no fueron significativos. Este estudio no pudo confirmar de forma estadísticamente significativa la hipótesis de la relación entre Akkermansia y el sobrepeso o la obesidad. Lo cual puede sugerir o una potencia del efecto menor del mismo al esperado, o la no relación directa o causal.(AU)

In recent years, Akkermansia muciniphila has gained prominence in scientific research due to its potential contribution to the regulation of immune response, insulin sensitivity, prevention of inflammatory diseases, and metabolic health. Specifically, its abundance has been inversely correlated with body weight, and its presence may have a beneficial effect on metabolism regulation. The aim of this study was to examine whether A. muciniphila was associated with BMI in individuals with gastrointestinal disorders. The results suggest that the abundance of A. muciniphila is very low in patients with gastrointestinal disorders (1.35%) and lower in individuals with overweight or obesity, although the results were not significant. This study could not confirm in a statistically significant way the hypothesis of the relationship between Akkermansia and overweight or obesity. Which may suggest either a lower power of the effect than expected, or no direct or causal relationship.(AU)

Gut microbiota disruption during sepsis and the influence of innate metabolites on sepsis prognosis / Alteración de la microbiota intestinal durante la sepsis y influencia de los metabolitos innatos en el pronóstico de la sepsis

Sepsis causes high mortality in intensive care units. Although there have been many studies on the gut microbiota in patients with sepsis, the impact of sepsis on the gut microbiota has not been directly determined because the treatment of sepsis also affects the gut microbiota. Therefore, we designed this animal experiment to explore gut microbiota alterations during sepsis. Mice were divided into two groups, mice that survived less than 3 days and mice that survived more than 3 days. Fecal samples collected on the day of cecal ligation and puncture (CLP), as well as on the 3rd and 7th days after CLP, were subjected to microbial community analysis and nontargeted metabolomics analysis. The results showed significantly lower bacterial diversity in fecal samples after CLP. At the genus level, the fecal samples obtained on the 3rd and 7th days after CLP exhibited significantly increased relative abundances of Bacteroides, Helicobacter, etc., and significantly decreased relative abundances of Alloprevotella, Prevotella, etc. Innate metabolite levels were significantly different in mice that survived less than 3 days and mice that survived more than 3 days. In conclusion, CLP-induced sepsis in mice changes the structure of the gut microbiome, and innate metabolites affect the prognosis of septic mice.(AU)

The intestinal microbiota of a Risso’s dolphin (Grampus griseus): possible relationships with starvation raised by macro-plastic ingestion / La microbiota intestinal del delfín gris (Grampus griseus): posibles relaciones con la inanición provocada por la ingestión de macroplásticos

Ingesting marine plastics is increasingly common in cetaceans, but little is known about their potential effects. Here, by utilizing 16S rRNA gene sequencing, we profiled the intestinal bacterial communities of a stranded Risso’s dolphin (Grampus griseus) which died because of the ingestion of rubber gloves. In this study, we explored the potential relationships between starvation raised by plastic ingestion with the dolphin gut microbiota. Our results showed significant differences in bacterial diversity and composition among the different anatomical areas along the intestinal tract, which may be related to the intestinal emptying process under starvation. In addition, the intestinal bacterial composition of the Risso’s dolphin showed both similarity and divergence to that of other toothed whales, suggesting potential roles of both host phylogeny and habitat shaping of the cetacean intestinal microbiome. Perhaps, the microbiota is reflecting a potentially disordered intestinal microbial profile caused by the ingestion of macro-plastics which led to starvation. Moreover, two operational taxonomic units (0.17% of the total reads) affiliated with Actinobacillus and Acinetobacter lwoffii were detected along the intestinal tract. These bacterial species may cause infections in immunocompromised dolphins which are malnourished. This preliminary study profiles the intestinal microbiota of a Risso’s dolphin, and provides an additional understanding of the potential relationships between starvation raised by ingesting macro-plastics with cetacean gut microbiota.(AU)

Early gut microbiological changes and metabolomic changes in patients with sepsis: a preliminary study / Cambios microbiológicos intestinales tempranos y cambios metabólicos en pacientes con sepsis: un estudio preliminar

The gut microbiota is closely related to the development of sepsis. The aim of this study was to explore changes in the gut microbiota and gut metabolism, as well as potential relationships between the gut microbiota and environmental factors in the early stages of sepsis. Fecal samples were collected from 10 septic patients on the first and third days following diagnosis in this study. The results showed that in the early stages of sepsis, the gut microbiota is dominated by microorganisms that are tightly associated with inflammation, such as Escherichia-Shigella, Enterococcus, Enterobacteriaceae, and Streptococcus. On sepsis day 3 compared to day 1, there was a significant decrease in Lactobacillus and Bacteroides and a significant increase in Enterobacteriaceae, Streptococcus, and Parabacteroides. Culturomica_massiliensis, Prevotella_7 spp., Prevotellaceae, and Pediococcus showed significant differences in abundance on sepsis day 1, but not on sepsis day 3. Additionally, 2-keto-isovaleric acid 1 and 4-hydroxy-6-methyl-2-pyrone metabolites significantly increased on sepsis day 3 compared to day 1. Prevotella_7 spp. was positively correlated with phosphate and negatively correlated with 2-keto-isovaleric acid 1 and 3-hydroxypropionic acid 1, while Prevotella_9 spp. was positively correlated with sequential organ failure assessment score, procalcitonin and intensive care unit stay time. In conclusion, the gut microbiota and metabolites are altered during sepsis, with some beneficial microorganisms decreasing and some pathogenic microorganisms increasing. Furthermore, Prevotellaceae members may play different roles in the intestinal tract, with Prevotella_7 spp. potentially possessing beneficial health properties and Prevotella_9 spp. potentially playing a promoting role in sepsis.(AU)

Gut microbial metabolites of dietary polyphenols and their potential role in human health and diseases

Polyphenols contribute as one of the largest groups of compounds among all the phytochemicals. Common sources of dietary polyphenols are vegetables, fruits, berries, cereals, whole grains, etc. Owing to their original form, they are difficult to get absorbed. Dietary polyphenols after undergoing gut microbial metabolism form bioaccessible and effective metabolites. Polyphenols and derived metabolites are all together a diversified group of compounds exhibiting pharmacological activities against cardiovascular, cancer, oxidative stress, inflammatory, and bacterial diseases. The formed metabolites are sometimes even more bioavailable and efficacious than the parent polyphenols. Studies on gut microbial metabolism of dietary polyphenols have introduced new approach for the use of polyphenol-rich food in the form of supplementary diet. This review provides insights on various aspects including classification of polyphenols, gut microbiota-mediated metabolism of polyphenols, chemistry of polyphenol metabolism, and pharmacological actions of gut microbial metabolites of polyphenols. It also suggests the use of polyphenols from marine source for the microbial metabolism studies. Till date, gut microbial metabolism of polyphenols from terrestrial sources is extensively studied as compared to marine polyphenols. Marine ecosystem is a profound but partially explored source of phytoconstituents. Among them, edible seaweeds contain high concentration of polyphenols, especially phlorotannins. Hence, microbial metabolism studies of seaweeds can unravel the pharmacological potential of marine polyphenol-derived metabolites. (AU)

Gut microbiota might mediate the benefits of high-fiber/acetate diet to cardiac hypertrophy mice

Continuously prolonged cardiac hypertrophy results in maladaptive myocardial remodeling, which affects cardiac function and can eventually lead to heart failure. Short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate, have been reported to be associated with cardiovascular diseases (CVD). Gut microbiota may mediate between dietary fiber and SCFA effects on cardiac hypertrophy. The mice model of isoproterenol (ISO)-induced cardiac hypertrophy was constructed and verified for physiological, functional, and fibrotic alterations in this study. Both high-fiber and acetate diet improved physiological indexes, ameliorated cardiac functions, and relieved fibrotic alterations in model mice hearts; collectively, cardiac hypertrophy in mice receiving both high-fiber and acetate diet improved. Following 16s rDNA sequencing and integrative bioinformatics, analyses indicated that both high-fiber and acetate diet caused alterations in mice gut microbiota compared with the ISO group, including OTU composition and abundance. In conclusion, high-fiber and acetate diet improve the physiological status, cardiac functions, and fibrotic alterations in ISO-induced hypertrophic mice. Besides, considering the alterations in mice gut microbiota in response to single ISO, both high-fiber and acetate diet treatment, gut microbiota might mediate the favorable benefits of both high-fiber and acetate diet on cardiac hypertrophy. (AU)

Lung microbiome: an emerging player in lung cancer pathogenesis and progression

The microbiome of the lungs, although until recently neglected, is now emerging as a potential contributor to chronic lung diseases, including cancer. Preclinical evidence suggests that the microbial burden of the lungs shapes the host immunity mechanisms and affects local antitumor immune responses. Studies of cohorts of patients with lung cancer reveal that different microbiome profiles are detected in patients with lung cancer compared to controls. In addition, an association between differential lung microbiome composition and distinct responses to immunotherapy has been suggested, yet, with limited data. Scarce evidence exists on the role of the lung microbiome in the development of metastases in the lungs. Interestingly, the lung microbiome is not isolated and interacts with the gut microbiome through a dynamic axis. Future research on the involvement of the lung microbiome in lung cancer pathogenesis and potential therapeutic implications is greatly anticipated (AU)

Estudio piloto para determinar la asociación entre la microbiota intestinal y la fractura de cadera por fragilidad / Pilot study to determine the association between gut microbiota and fragility hip fracture

Introducción: Las fracturas de cadera son la causa más frecuente de ingreso hospitalario en los servicios de ortopedia de Europa y suponen un importante problema sanitario. Por ello, es de gran interés identificar factores de riesgo adicionales que nos ayuden a comprender mejor la fisiopatología de estas fracturas y a mejorar nuestra capacidad preventiva. Existen datos suficientes para apoyar la teoría de la modulación de la masa ósea por la microbiota intestinal (osteomicrobiología); sin embargo, faltan estudios clínicos en humanos que relacionen directamente la microbiota con el riesgo de fractura de cadera. Material y métodos: Estudio observacional, analítico, de casos y controles. La muestra consta de 50 pacientes y se distribuye de la siguiente manera: 25 pacientes ancianos con fractura de cadera por fragilidad y 25 controles sanos sin fractura. Se analizó la microbiota intestinal mediante extracción de ADN de muestras de heces y secuenciación del ADN ribosómico 16S tras la generación de bibliotecas de genes. Resultados: La diversidad alfa reveló una elevación de los estimadores para el nivel taxonómico de clase en el grupo de fracturas de cadera. Los órdenes Bacteroidales, Oscillospirales, Lachnospirales, Peptostreptococcales-Tissierellales y Enterobacterales fueron los órdenes dominantes en ambos grupos. En los pacientes con fractura, se observó un aumento porcentual significativo del orden de Bacteroidales (p<0,001) y Peptostreptococcales-Tissierellales (p<0,005), así como una disminución de las del orden Lachnospirales (p<0,001) respecto a los controles. Conclusiones:Este estudio ha encontrado una asociación entre una microbiota específica en pacientes ancianos con fractura de cadera por fragilidad. Estos hallazgos abren la puerta a nuevas estrategias para prevenir las fracturas de cadera. Es posible que la modificación de la microbiota mediante probióticos se revele como un método eficaz para reducir el riesgo de fractura de cadera.(AU)

Introduction: Hip fractures are the most common cause of hospital admission to orthopaedic departments in Europe and they generate a major health problem. Therefore, it is of great interest to identify additional risk factors that will help us to better understand the pathophysiology of these fractures and improve our preventive capacity. There is sufficient data to support the theory of modulation of bone mass by gut microbiota (osteomicrobiology); however, there is a lack of human clinical studies directly linking microbiota to hip fracture risk. Material and methods: Observational, analytical, case–control study. The sample consisted of 50 patients and it was distributed as follows: 25 elderly patients with fragility hip fracture and 25 subjects without fracture. The intestinal microbiota was determined by DNA extraction from stool samples and 16S ribosomal DNA sequencing after generation of gene libraries. Results: Alpha diversity revealed an elevation of the estimators for the taxonomic class level in the hip fracture group. The orders Bacteroidales, Oscillospirales, Lachnospirales, Peptostreptococcales-Tissierellales and Enterobacterales were the dominant orders in both groups. In patients with fracture, a significant percentage increase in the orders Bacteroidales (p<.001) and Peptostreptococcales-Tissierellales (p<.005) was observed, as well as a decrease in the orders Lachnospirales (p<.001) compared to controls. Conclusions: This study has found an association between a specific microbiota in elderly patients with fragility hip fracture. These findings open the door to new strategies to prevent hip fractures. Modification of the microbiota through probiotics may prove to be an effective method to reduce the risk of hip fracture.(AU)

[Translated article] Pilot study to determine the association between gut microbiota and fragility hip fracture / Estudio piloto para determinar la asociación entre la microbiota intestinal y la fractura de cadera por fragilidad

Introducción: Las fracturas de cadera son la causa más frecuente de ingreso hospitalario en los servicios de ortopedia de Europa y suponen un importante problema sanitario. Por ello, es de gran interés identificar factores de riesgo adicionales que nos ayuden a comprender mejor la fisiopatología de estas fracturas y a mejorar nuestra capacidad preventiva. Existen datos suficientes para apoyar la teoría de la modulación de la masa ósea por la microbiota intestinal (osteomicrobiología); sin embargo, faltan estudios clínicos en humanos que relacionen directamente la microbiota con el riesgo de fractura de cadera. Material y métodos: Estudio observacional, analítico, de casos y controles. La muestra consta de 50 pacientes y se distribuye de la siguiente manera: 25 pacientes ancianos con fractura de cadera por fragilidad y 25 controles sanos sin fractura. Se analizó la microbiota intestinal mediante extracción de ADN de muestras de heces y secuenciación del ADN ribosómico 16S tras la generación de bibliotecas de genes. Resultados: La diversidad alfa reveló una elevación de los estimadores para el nivel taxonómico de clase en el grupo de fracturas de cadera. Los órdenes Bacteroidales, Oscillospirales, Lachnospirales, Peptostreptococcales-Tissierellales y Enterobacterales fueron los órdenes dominantes en ambos grupos. En los pacientes con fractura, se observó un aumento porcentual significativo del orden de Bacteroidales (p<0,001) y Peptostreptococcales-Tissierellales (p<0,005), así como una disminución de las del orden Lachnospirales (p<0,001) respecto a los controles. Conclusiones:Este estudio ha encontrado una asociación entre una microbiota específica en pacientes ancianos con fractura de cadera por fragilidad. Estos hallazgos abren la puerta a nuevas estrategias para prevenir las fracturas de cadera. Es posible que la modificación de la microbiota mediante probióticos se revele como un método eficaz para reducir el riesgo de fractura de cadera.(AU)

Introduction: Hip fractures are the most common cause of hospital admission to orthopaedic departments in Europe and they generate a major health problem. Therefore, it is of great interest to identify additional risk factors that will help us to better understand the pathophysiology of these fractures and improve our preventive capacity. There is sufficient data to support the theory of modulation of bone mass by gut microbiota (osteomicrobiology); however, there is a lack of human clinical studies directly linking microbiota to hip fracture risk. Material and methods: Observational, analytical, case–control study. The sample consisted of 50 patients and it was distributed as follows: 25 elderly patients with fragility hip fracture and 25 subjects without fracture. The intestinal microbiota was determined by DNA extraction from stool samples and 16S ribosomal DNA sequencing after generation of gene libraries. Results: Alpha diversity revealed an elevation of the estimators for the taxonomic class level in the hip fracture group. The orders Bacteroidales, Oscillospirales, Lachnospirales, Peptostreptococcales-Tissierellales and Enterobacterales were the dominant orders in both groups. In patients with fracture, a significant percentage increase in the orders Bacteroidales (p<.001) and Peptostreptococcales-Tissierellales (p<.005) was observed, as well as a decrease in the orders Lachnospirales (p<.001) compared to controls. Conclusions: This study has found an association between a specific microbiota in elderly patients with fragility hip fracture. These findings open the door to new strategies to prevent hip fractures. Modification of the microbiota through probiotics may prove to be an effective method to reduce the risk of hip fracture.(AU)

Prevalencia de síntomas gastrointestinales en trastornos del espectro del autismo: un metaanálisis / Prevalence of gastrointestinal symptoms in autism spectrum disorder: A meta-analysis

Introducción: Se ha descrito una elevada prevalencia de síntomas gastrointestinales (GI) en los niños y adolescentes con trastornos del espectro del autismo (TEA). Además, se ha relacionado la presencia de dichos síntomas con mayor gravedad de la clínica TEA. Sin embargo, la frecuencia de síntomas GI en niños y adolescentes con TEA es muy variable a lo largo de los estudios y no se conoce su verdadera prevalencia. Por tanto, el objetivo del presente trabajo fue estimar la prevalencia de síntomas GI en niños y adolescentes con TEA. Material y método: Se realizó un metaanálisis siguiendo las directrices PRISMA. Se llevó a cabo una búsqueda sistemática rápida de nuevos estudios clínicos y observacionales desde agosto de 2012 en PubMed. Los análisis estadísticos se realizaron con el software R. Resultados: De 91 artículos potencialmente elegibles, solo 8 cumplieron nuestros criterios de inclusión. La prevalencia de síntomas GI osciló entre el 0 y el 69%, con una prevalencia general estimada del 33% (IC del 95%: 13-57%), cifra superior a la reportada por un metaanálisis previo para la población general pediátrica. Esta diferencia es todavía mayor al comparar específicamente los estudios que emplean la versión pediátrica del cuestionario ROMA III (QPGS-ROME III). Conclusiones: Estos resultados confirman la hipótesis de que existe una prevalencia superior de síntomas GI funcionales en el TEA frente a sus coetáneos neurotípicos. (AU)

Introduction: A high prevalence of gastrointestinal (GI) symptoms has been described in children and adolescents with autism spectrum disorder (ASD). In addition, there is evidence that presence of GI symptoms is associated to greater severity of ASD. However, the frequency of GI symptoms in children and adolescents with ASD varies widely across studies, and their true prevalence is unknown. Therefore, the objective of this study was to estimate the prevalence of GI symptoms in children and adolescents with ASD. Material and method: We conducted a meta-analysis following the PRISMA guidelines. We carried out a rapid systematic search for recent clinical and observational studies published from August 2012 in PubMed. The statistical analyses were performed with the software R. Results: Of 91 potentially eligible articles, only 8 met our inclusion criteria. The prevalence of GI symptoms ranged between 0% and 69%, with an estimated general prevalence of 33% (95% CI, 13%-57%), higher than that reported by a previous meta-analysis for the general paediatric population. This difference is even greater in the specific comparison of studies that applied the paediatric version of the ROME III questionnaire (QPGS-ROME III). Conclusions: The results confirmed the hypothesis that there is a higher prevalence of functional GI symptoms in paediatric patients with ASD compared to their neurotypical peers. (AU)

Lactobacillus rhamnosus GG treatment potentiates ethanol-induced behavioral changes through modulation of intestinal epithelium in Danio rerio / El tratamiento con Lactobacillus rhamnosus GG potencia los cambios de comportamiento inducidos por etanol a través de la modulación del epitelio intestinal en Danio rerio

The gut-brain axis directly regulates the brain homeostatic environment; an imbalance in gut microbial composition following ethanol exposure is maleficent. In this context, involvement of probiotics as prophylactic intervention against ethanol-induced neurotoxicity is elusive in the literature. Therefore, the present study was aimed to determine the impact of chronic ethanol exposure on the neurobehavioral response of zebrafish and possible neuroprotection through co-supplementation of probiotic Lactobacillus rhamnosus GG (LGG). Zebrafish were divided into naive, control, ethanol (0.01% v/v), LGG, and ethanol co-supplemented with LGG groups. Neurobehavioral assessment was performed after 7 days of chronic waterborne exposure to ethanol with LGG co-supplementation followed by histopathological studies. The findings indicated that there was a clear alteration in locomotor activity and habitat preference, with animals preferentially migrating toward altered zones on exposure to ethanol. However, co-supplementation of LGG showed restoration against ethanol-induced neurobehavioral and cognitive dysfunction. Brain tissue pyknosis and intestinal epithelial disruption were significantly mitigated on LGG co-supplementation against ethanol in zebrafish. The present study provides a novel approach toward supplementation of probiotics such as LGG in modulation of gut commensal microbiota influencing zebrafish behavior. Moreover, the findings delineate the possible role of probiotics as a curative administration to counter ethanol-persuaded neurological outcomes.(AU)