Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child

Wijeyesekera, Anisha; Wagner, Josef; Goffau, Marcus C. de; Thurston, Sarah; Sabino, Adilson Rodrigues; Zaher, Sara; White, Deborah; Ridout, Jenna; Peters, Mark; Ramnarayan, Padmanabhan; Branco, Ricardo Garcia; Török, M. Estée; Valla, Frédéric V.; Klein, Nigel; Frost, Gary; Parkhill, Julian; Holmes, Elaine; Pathan, Nazima

doi:10.1097/ccm.0000000000003841

Cited by 22 publications

(40 citation statements)

References 32 publications

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“…Studies conducted in mice have shown that gut bacteria alter the distribution of free amino acids in the gastrointestinal tract and affect the bioavailability of amino acids for the host 48 . When the gut microbiota is healthy (eubiotic status), a trophic network is maintained that is suitable for the fermentation of substances present in the intestine, but when the gut microbial balance is disrupted (dysbiotic status), this trophic network is disrupted and the community shows poor fermentation efficiency 49 . Thus, higher concentrations of amino acids in the intestine are thought to be the result of incomplete fermentation.…”

Section: Resultsmentioning

confidence: 99%

Longitudinal evaluation of fecal microbiota transplantation for ameliorating calf diarrhea and improving growth performance

et al. 2021

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Calf diarrhea is associated with enteric infections, and also provokes the overuse of antibiotics. Therefore, proper treatment of diarrhea represents a therapeutic challenge in livestock production and public health concerns. Here, we describe the ability of a fecal microbiota transplantation (FMT), to ameliorate diarrhea and restore gut microbial composition in 57 growing calves. We conduct multi-omics analysis of 450 longitudinally collected fecal samples and find that FMT-induced alterations in the gut microbiota (an increase in the family Porphyromonadaceae) and metabolomic profile (a reduction in fecal amino acid concentration) strongly correlate with the remission of diarrhea. During the continuous follow-up study over 24 months, we find that FMT improves the growth performance of the cattle. This first FMT trial in ruminants suggest that FMT is capable of ameliorating diarrhea in pre-weaning calves with alterations in their gut microbiota, and that FMT may have a potential role in the improvement of growth performance.

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Section: Resultsmentioning

confidence: 99%

Longitudinal evaluation of fecal microbiota transplantation for ameliorating calf diarrhea and improving growth performance

et al. 2021

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“…[ 1 2 3 ] Critical illness is considered one of the major environmental influences that can impact the gut environment. [ 4 ] It is associated with pathophysiological effects causing damage to the intestinal microbiome. These include ischemia, hypoxia and hypotension along with the iatrogenic effects of therapeutic agents and the lack of enteral feeds.…”

Section: Introductionmentioning

confidence: 99%

Nutrition and the gut microbiome during critical illness: A new insight of nutritional therapy

Zaher

2020

Saudi J Gastroenterol

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Changes in the microbiome in response to environmental influences can affect the overall health. Critical illness is considered one of the major environmental factors that can potentially influence the normal gut homeostasis. It is associated with pathophysiological effects causing damage to the intestinal microbiome. Alteration of intestinal microbial composition during critical illness may subsequently compromise the integrity of the intestinal epithelial barrier and intestinal mucosa absorptive function. Many factors can impact the microbiome of critically ill patients including ischemia, hypoxia and hypotension along with the iatrogenic effects of therapeutic agents and the lack of enteral feeds. Factors related to disease state and medication are inevitable and they are part of the intensive care unit (ICU) exposure. However, a nutritional intervention targeting gut microbiota might have the potential to improve clinical outcomes in the critically ill population given the extensive vascular and lymphatic links between the intestines and other organs. Although nutrition is considered an integral part of the treatment plan of critically ill patients, still the role of nutritional intervention is restricted to improve nitrogen balance. What is dismissed is whether the nutrients we provide are adequate and how they are processed and utilised by the host and the microbiota. Therefore, the goal of nutrition therapy during critical illness should be extended to provide good quality feeds with balanced macronutrient content to feed up the entire body including the microbiota and host cells. The main aim of this review is to examine the current literature on the effect of critical illness on the gut microbiome and to highlight the role of nutrition as a factor affecting the intestinal microbiome-host relationship during critical illness.

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“…The gut microbiome of patients in the intensive care unit (ICU) can be vastly differently from those of healthy individuals (8,9). In critically ill patients, dysbiosis, which is a disruption in the microbiome homeostasis, is common.…”

Section: Introductionmentioning

confidence: 99%

“…In critically ill patients, dysbiosis, which is a disruption in the microbiome homeostasis, is common. There is a loss of both alpha and beta diversity, as well as predominance of certain bacterial taxa, in these patients (8)(9)(10). Alpha diversity is a measurement of how rich an ecological bacterial community and beta diversity is the degree of difference of one community from another (11,12).…”

Section: Introductionmentioning

confidence: 99%

Enteral feeding and the microbiome in critically ill children: a narrative review

Fan

Lee²

2021

Transl Pediatr

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This narrative review summarizes our current knowledge on the interplay between enteral nutrition (EN) and gut microbiota in critically ill children, using examples from two commonly encountered diagnoses in the pediatric intensive care unit (PICU): severe sepsis and acute respiratory distress syndrome (ARDS). This review will also highlight potential areas of therapeutic interventions that should be explored in future studies.Background: Critically ill children display extreme dysbiosis in their gut microbiome. Factors within the PICU that are often associated with dysbiosis include the use of broad-spectrum antibiotics, protonpump inhibitors (PPIs), intravenous morphine, and fasting. Dysbiosis can potentially lead to adverse clinical outcomes (e.g., nosocomial infection, and prolonged hospitalization). EN may modulate dysbiosis. The gut microbiota is involved in the breaking down of macronutrients, mainly carbohydrates and proteins.Fermentation of undigestible carbohydrate (e.g., inulin and oligosaccharides), and amino acids by large intestine microbiota produces short chain fatty acids (SCFAs). SCFAs serve as the main fuel source for enterocytes and help to maintain healthy gut lining. Changes to selected components of macronutrients can result in alterations in gut microbiome and have potentially beneficial effects in patients in the PICU.Methods: A comprehensive search of the MEDLINE, Cochrane Library and Google Scholar databases was conducted using appropriate MESH terms and keywords. In this narrative review, we provide a summary of current knowledge on effect of EN on gut microbiota in pediatric studies, but also describes animal-and labbased, as well as adult studies where relevant. Conclusions:The gut microbiome can be altered by dietary modifications and common PICU practices and treatment. Although there are strong associations in restoring eubiosis and improvement in clinical outcomes, proving causality remains challenging. Further microbiome research is needed to provide mechanistic insights into the impact of the ever changing gut microbiome. In the future, new microbiota targeted therapies could potentially be the treatment of challenging PICU conditions and restore homeostasis in these children.

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Multi-Compartment Profiling of Bacterial and Host Metabolites Identifies Intestinal Dysbiosis and Its Functional Consequences in the Critically Ill Child

Abstract: Supplemental Digital Content is available in the text.

Cited by 22 publications

References 32 publications

Longitudinal evaluation of fecal microbiota transplantation for ameliorating calf diarrhea and improving growth performance

Longitudinal evaluation of fecal microbiota transplantation for ameliorating calf diarrhea and improving growth performance

Nutrition and the gut microbiome during critical illness: A new insight of nutritional therapy

Enteral feeding and the microbiome in critically ill children: a narrative review

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