Leveraging the microbiome in the treatment of sepsis: potential pitfalls and new perspectives

Biemond, Jason J.; McDonald, Braedon; Haak, Bastiaan W.

doi:10.1097/mcc.0000000000001019

Cited by 3 publications

(3 citation statements)

References 60 publications

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“…Third, the production of beneficial microbial products (e.g., SCFAs) is reduced. These metabolites may be involved in the initiation of the innate and adaptive immune system to protect distant organs from infection ( 48 ). Fourth, once sepsis is established, the gut microbiome deteriorates and leads to increased susceptibility to visceral organ dysfunction ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota and sepsis and sepsis-related death: a Mendelian randomization investigation

Shang,

Zhang,

Qian

et al. 2024

Front. Immunol.

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BackgroundIt is unclear what the causal relationship is between the gut microbiota and sepsis. Therefore, we employed Mendelian randomization (MR) to determine whether a causal link exists between the two.MethodsThis study used publicly available genome-wide association studies (GWAS) summary data of gut microbiota, sepsis, sepsis (critical care), and sepsis (28-day death in critical care) to perform a two-sample MR analysis. To ensure the robustness of the results, we also conducted a sensitivity analysis.ResultsFor sepsis susceptibility, inverse variance weighted (IVW) estimates revealed that Victivallales (OR = 0.86, 95% CI, 0.78–0.94, p = 0.0017) was protective against sepsis, while Lentisphaerae (OR = 0.89, 95% CI, 0.80–0.99), Gammaproteobacteria (OR = 1.37, 95% CI, 1.08–1.73), Clostridiaceae1 (OR = 1.21, 95% CI, 1.04–1.40), RuminococcaceaeUCG011 (OR = 1.10, 95% CI, 1.01–1.20), Dialister (OR = 0.85, 95% CI, 0.74–0.97), and Coprococcus2 (OR = 0.81, 95% CI, 0.69–0.94) presented a suggestive association with the development of sepsis (all p < 0.05). For sepsis (critical care), IVW estimates indicated that Lentisphaerae (OR = 0.70, 95% CI, 0.53–0.93), Victivallales (OR = 0.67, 95% CI, 0.50–0.91), Anaerostipes (OR = 0.49, 95% CI, 0.31–0.76), LachnospiraceaeUCG004 (OR = 0.51, 95% CI, 0.34–0.77), and Coprococcus1 (OR = 0.66, 95% CI, 0.44–0.99) showed a suggestive negative correlation with sepsis (critical care) (all p < 0.05). For sepsis (28-day death in critical care), IVW estimates suggested that four bacterial taxa had a normally significant negative correlation with the risk of sepsis-related death, including Victivallales (OR = 0.54, 95% CI, 0.30–0.95), Coprococcus2 (OR = 0.34, 95% CI, 0.14–0.83), Ruminiclostridium6 (OR = 0.43, 95% CI, 0.22–0.83), and Coprococcus1 (OR = 0.45, 95% CI, 0.21–0.97), while two bacterial taxa were normally significantly positively linked to the risk of sepsis-related death, namely, Mollicutes (OR = 2.03, 95% CI, 1.01–4.08) and Bacteroidales (OR = 2.65, 95% CI, 1.18–5.96) (all p < 0.05). The robustness of the above correlations was verified by additional sensitivity analyses.ConclusionThis MR research found that several gut microbiota taxa were causally linked to the risk of sepsis, sepsis in critical care, and sepsis-related 28-day mortality in critical care.

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Section: Discussionmentioning

confidence: 99%

Gut microbiota and sepsis and sepsis-related death: a Mendelian randomization investigation

Shang,

Zhang,

Qian

et al. 2024

Front. Immunol.

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“…Haak et al [7] and Bos et al [8] focus on the emerging role of the microbiome in critical illness. The gut microbiome of most critically ill patients undergoes significant changes due to various internal (e.g.…”

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confidence: 99%

“…Haak et al [7] give an overview of the current understanding of microbiota-based therapies in sepsis and argue that -despite the recent negative study results -it is important to continue working towards integrating these approaches into clinical practice. The development and use of next-generation probiotics may offer a new and effective way to manipulate bacterial communities and potentially improve patient outcomes in sepsis [7,12]. Bos et al [8] discuss the growing understanding of the gutlung axis, including the potential impact of the gut microbiome, on lung function in critical illness.…”

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confidence: 99%

The power of the gut in critical care

Wiersinga

2023

Current Opinion in Critical Care

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Nutritional and metabolic modulation of inflammation in critically ill patients: a narrative review of rationale, evidence and grey areas

Rousseau,

Martindale

2024

Ann. Intensive Care

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Background Inflammation is the hallmark of critical illness and triggers the neuro-endocrine stress response and an oxidative stress. Acute inflammation is initially essential for patient’s survival. However, ongoing or exaggerated inflammation, due to persistent organ dysfunction, immune dysfunction or poor inflammation resolution, is associated to subsequent hypermetabolism and hypercatabolism that severely impact short and long-term functional status, autonomy, as well as health-related costs. Modulation of inflammation is thus tempting, with the goal to improve the short- and long-term outcomes of critically ill patients. Findings Inflammation can be modulated by nutritional strategies (including the timing of enteral nutrition initiation, the provision of some specific macronutrients or micronutrients, the use of probiotics) and metabolic treatments. The most interesting strategies seem to be n-3 polyunsaturated fatty acids, vitamin D, antioxidant micronutrients and propranolol, given their safety, their accessibility for clinical use, and their benefits in clinical studies in the specific context of critical care. However, the optimal doses, timing and route of administration are still unknown for most of them. Furthermore, their use in the recovery phase is not well studied and defined. Conclusion The rationale to use strategies of inflammation modulation is obvious, based on critical illness pathophysiology and based on the increasingly described effects of some nutritional and pharmacological strategies. Regretfully, there isn’t always substantial proof from clinical research regarding the positive impacts directly brought about by inflammation modulation. Some arguments come from studies performed in severe burn patients, but such results should be transposed to non-burn patients with caution. Further studies are needed to explore how the modulation of inflammation can improve the long-term outcomes after a critical illness.

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Leveraging the microbiome in the treatment of sepsis: potential pitfalls and new perspectives

Cited by 3 publications

References 60 publications

Gut microbiota and sepsis and sepsis-related death: a Mendelian randomization investigation

Gut microbiota and sepsis and sepsis-related death: a Mendelian randomization investigation

The power of the gut in critical care

Nutritional and metabolic modulation of inflammation in critically ill patients: a narrative review of rationale, evidence and grey areas

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