Membership and Behavior of Ultra-Low-Diversity Pathogen Communities Present in the Gut of Humans during Prolonged Critical Illness

Abstract

We analyzed the 16S rRNA amplicon composition in fecal samples of selected patients during their prolonged stay in an intensive care unit (ICU) and observed the emergence of ultra-low-diversity communities (1 to 4 bacterial taxa) in 30% of the patients. Bacteria associated with the genera Enterococcus and Staphylococcus and the family Enterobacteriaceae comprised the majority of these communities. The composition of cultured species from stool samples correlated to the 16S rRNA analysis and additionally revealed the emergence of Candida albicans and Candida glabrata in ~75% of cases. Four of 14 ICU patients harbored 2-member pathogen communities consisting of one Candida taxon and one bacterial taxon. Bacterial members displayed a high degree of resistance to multiple antibiotics. The virulence potential of the 2-member communities was examined in C. elegans during nutrient deprivation and exposure to opioids in order to mimic local conditions in the gut during critical illness. Under conditions of nutrient deprivation, the bacterial members attenuated the virulence of fungal members, leading to a “commensal lifestyle.” However, exposure to opioids led to a breakdown in this commensalism in 2 of the ultra-low-diversity communities. Application of a novel antivirulence agent (phosphate-polyethylene glycol [Pi-PEG]) that creates local phosphate abundance prevented opioid-induced virulence among these pathogen communities, thus rescuing the commensal lifestyle. To conclude, the gut microflora in critically ill patients can consist of ultra-low-diversity communities of multidrug-resistant pathogenic microbes. Local environmental conditions in gut may direct pathogen communities to adapt to either a commensal style or a pathogenic style.

Hospitalization Type and Subsequent Severe Sepsis

“…Rather than measure microbiome composition directly, we studied three major events that result in increasing degrees of probable dysbiosis: (1) hospitalization without infection, (2) hospitalization with infection, and (3) hospitalization with Clostridium difficile infection (CDI) (17)(18)(19). We hypothesized that all hospitalized patients experience diet, sleep, and lifestyle disruptions that perturb microbiome homeostasis (20), as confirmed through direct measurement of fecal diversity in hospitalized patients (17,18).…”

Microbiota intestinal y ácidos grasos de cadena corta en pacientes críticos

“…Zaborin et al (46) evaluaron los cambios ocurridos en la MI a través del tiempo durante enfermedades críticas prolongadas. El estudio se realizó en 14 pacientes que representaban un grupo diverso en una UCI con diferente tiempo de permanencia.…”

“…De igual manera, con ambas técnicas se pudo evidenciar la ineficacia de los tratamientos antibióticos agresivos utilizados para eliminar los patógenos, independientemente de su sensibilidad a los compuestos administrados. Asimismo, los resultados permitieron demostrar que los factores del cuidado crítico usados para el tratamiento de pacientes en UCI (esteroides, hormonas y opioides) pueden inducir virulencia bacteriana (46).…”

“…Se propone que el microbioma intestinal en pacientes críticos puede ser considerado un "órgano dañado", debido a que su masa celular principal, la microbiota normal, está alterada y dominada por microorganismos patógenos que pueden ser una fuente de constante amenaza para su diseminación (46). Con los estudios que buscan establecer la relación entre el microbioma humano y la salud o la predisposición a enfermedades, se espera que 1) proporcionen los conceptos fundamentales para comprender como la MI influye en la enfermedad, 2) contribuyan al desarrollo de técnicas para monitorear la evolución de las enfermedades, 3) proporcionen una base para los tratamientos personalizados, y 4) señalen futuras vías terapéuti-cas (8).…”

Insoluble fiber and intestinal microbiota metabolism

“…Recently, cellulose ameliorated colitis in mice [6], and wheat bran improved quality of life and Crohn's disease symptoms in humans [7]. Regarding microbial gene expression, the phytase activity of wheat bran is unsurpassed [8]; thus, wheat bran may potentially prevent shifts in microbial gene expression toward invasiveness, by boosting phosphate availability [9].…”