Contemplating the Bibliometric Data Onto Sepsis and Gut Microbiome: Mapping Trends, Collaborations, and Global Contributions

Sepsis, a life-threatening condition resulting from the body’s dysregulated response to infection (Singer et al. 2016), is a significant contributor to mortality in severe patients, with a mortality rate of up to 29.0%. Septic shock is a severe form of sepsis and is by the means of serious, circulatory, cellular, and metabolic abnormality, because of the hypotension, which is not corrected by the fluid resuscitation, that accounts for the increase in the death rate (Liu et al. 2022). The pathogenesis of sepsis involves a complex interplay of infection, inflammation, immunity, coagulation, and, notably, intestinal dysfunction and flora imbalance (Haak and Wiersinga 2017, Adelman et al. 2020). Among critically ill patients, the gut microbiome has gained prominence in sepsis research, drawing increasing attention from intensive care unit (ICU) physicians seeking ways to enhance gut microbiome health for improved survival in patients with sepsis.

The gut microbiome comprises the interaction between intestinal flora and the host, encompassing the intestine, intestinal epithelial cells, secretions, ingested food, and nutrients (Cresci and Bawden 2015, Heintz-Buschart and Wilmes 2018). Of particular significance is the role of intestinal flora, which plays a crucial rolein nutrient metabolism, digestion, absorption, resistance to external bacterial colonization, anti-tumor activities, and maintenance of the intestinal barrier and immune function (Jandhyala et al. 2015, Hills et al. 2019). The pathogenesis of sepsis involves the interaction of infection, inflammation, immune dysfunction, coagulation defect, and the disrupted blood-gut barrier is the central part of it. In sepsis, gut permeability increases and the gut bacteria and endotoxins can migrate out of the gut into the bloodstream, which sparks the body’s inflammatory reaction and organ dysfunction. The blood-gut barrier’s impairment gives rise to the difficult immune system situation, moreover, the vicious cycle of inflammation – bacterial multiplication – and the further endotoxin that is added into the bloodstream. Thus, the restoration of the blood-gut barrier is being the key issue in treating sepsis as well as the gastrointestinal microbiome as a component that participates in this process providing the default barrier and the health of the mucosal wall (Dubin 2018). Consequently, investigating the relationship between sepsis and the gut microbiome has become a key focus of numerous studies.

Current research on sepsis and the gut microbiome takes various angles, with some studies examining microbiome composition (Miller et al. 2021), others exploring microbiota dynamics (Kullberg et al. 2021), and additional investigations considering broader aspects of flora involvement. While reviews provide comprehensive summaries and analyses of the interplay between sepsis and the gut microbiome (Tourelle et al. 2021, Zanza et al. 2022), a macroscopic analysis of the overall research landscape in this field is lacking.

To address this gap, our study utilizes bibliometric methods in literature research to systematically analyze published works. Through retrieval, statistical processing, and comprehensive analysis of relevant literature, we aim to unveil the current state of research on the gut microbiome of sepsis patients. Bibliometric enables exploration of key aspects such as geographic distribution of research, institutional affiliations, prominent researchers, favored journals, and prevalent keywords within the literature corpus (Brandt et al. 2019). This methodological approach aims to provide an in-depth understanding of the current focus and developmental trajectory in the expansive field of sepsis and gut microbiome research.

The outcomes of this study affirm the increasing research focus on the association between sepsis and the microbiome over the past decade. The upward trajectory in published literature reflects the growing acknowledgment of the clinical importance of investigating infectious diseases, particularly sepsis (Coopersmith et al. 2018). The observed dominance of the United States and China in the quantity of published literature underscores their significant contributions to the field. The United States not only exhibits a substantial publication volume but also a noteworthy centrality score, indicating a considerable influence within the scholarly network. Conversely, while China demonstrates prolific publication, its lower centrality score suggests potential for increased collaborative engagement on the international stage (Rhee et al. 2017).

Analysis of research institutions reveals the prevalence of European and American entities, with the University of California emerging as a central hub for collaborative research in this field. Noteworthy contributors include Fang Min and Wiersinga WJ from the University of Amsterdam, with Prof Wiersinga leading in both publication volume and collaborative endeavors. Journal analysis indicates that while research in this field is present in authoritative journals, there is a prevalent focus on severe diseases, microbiology, and immunology publications (Wiersinga and van der Poll 2022). This thematic alignment underscores the clinical and microbiological dimensions inherent in sepsis and gut microbiome studies. Examining the microecology, our study underscores the pivotal role of gut microbiome in human health. The intricate interplay of microbial entities, including Bacteroides, Bifidobacterium, and Lactobacillus, highlights their diverse contributions to nutrient metabolism, immune function, and intestinal barrier maintenance (Schmidt et al. 2018).

In the context of sepsis, our analysis reveals distinct alterations in the gut microbiome, characterized by reduced diversity, altered abundance of key microbial groups, and overgrowth of pathogenic bacteria. This dysbiosis correlates positively with the mortality risk in patients exhibiting systemic inflammatory response syndrome and multiple organ dysfunction syndrome (Shimizu et al. 2011). The use of broad-spectrum antibiotics, a common therapeutic approach in sepsis, emerges as a significant factor contributing to gut microbiome imbalance (Condotta et al. 2013). This disruption is not only related to the duration of antibiotic use but also to specific antibiotic types and/or combinations of antibiotics, such as ceftriaxone and imipenem, with implications for the risk of opportunistic infections and antibiotic-associated complications (Haak and Wiersinga 2017). Clinical strategies for mitigating gut microbiome imbalance include judicious antibiotic use, supplementation with microecological agents, early enteral nutrition, and fecal flora transplantation (He et al. 2013, Wang et al. 2019; Ramirez et al. 2020, Johnstone et al. 2021, Cheema et al. 2022). These interventions aim to preserve microbial diversity, restore ecological balance, and improve patient outcomes.

Apart from the bacterial factors in the gut microbiota, the contribution of fungus in keeping the microorganism balance is a very important aspect that should be taken into consideration. Fungal species, primarily Candida, Aspergillus, and Zygomycetes, can considerably affect the intestinal microbiome. For example, Candida albicans is often related to dysbiosis, especially in people with weakened immune systems or those who are on the long-term use of broad-spectrum antibiotics. This non-optimal situation in the microbiota causes hypoproliferation, inflammation as well as negative changes in the intestinal barrier. Besides, the Aspergillus genus, although it isn’t usually mentioned in gut health conversations, has been associated with dysbiosis in serious infections and it can disturb the microbiome community’s normal activities in the gastrointestinal tract. Recognizing the role that fungi play in these processes is critically important if we are to develop successful strategies to fight against dysbiosis in sepsis patients (Chin et al. 2020).

In addition to macroscopic tendencies found in sepsis and gut microbiome research, the discovery of the etiological agents is very important in the differential diagnosis of sepsis microbe contributors. In our bibliometric style, we did not define independent causative pathogens, but prior studies often find that bacterial species, such as Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus are common etiological factors in bacterial sepsis. These pathogens are frequently referred to disturbances in the gut microbiota, which are advantageous for the proliferation of pathogenic species and disadvantageous from the perspective of a high microbial diversity ratio. Bacteria, specifically Candida albicans, are also the predisposing factors for sepsis in cases of immunocompromised patients and they are associated with specific dysbiosis patterns in the gut microbiome (Jawhara 2022). The limitation in the bacterial and fungal etiologies can be the potential information on the dysbiosis and thus, the development of specific therapeutic strategies targeting the patient’s microbes may prove to be the solution.

While this study provides a comprehensive macroscopic overview of the literature, its limitations include the lack of in-depth analysis of individual studies, interventions, and recent advancements. Additionally, the exclusion of non-English literature from the SCI-E database introduces a potential source of omission, emphasizing the need for a more inclusive approach to capture global contributions. The surge in research on the relationship between sepsis and gut microbiome signifies a burgeoning field with evolving clinical implications. The dominance of the United States in this research landscape underscores its leadership role. Future directions should prioritize evidencebased investigations, clinical trials, and prospective studies. Enhanced international collaboration, particularly involving Chinese researchers, holds promise for advancing the understanding and management of sepsis through the lens of gut microbiome dynamics.

Current study delves into the expanding landscape of sepsis and gut microbiome research, analyzing 2485 articles spanning diverse publication types and thematic concentrations. The temporal analysis reveals a consistent increase in publications, reflecting a burgeoning interest and impact within the scientific community. The dominance of the United States in both quantity and centrality underscores its pivotal role, with significant contributions from France, the United Kingdom, and others. Authorship analysis highlights Prof Wiersinga’s prolific output and impact, while institutional dynamics and international collaboration further enrich the scholarly network. The examination of journals and keywords elucidates the thematic focus on microbiome-related concepts. The findings underscore altered gut microbiome dynamics in patients with sepsis, influenced by factors like antibiotic use, with clinical strategies proposed for mitigation. The study’s limitations, including language exclusivity and the need for more detailed analyses, are acknowledged. Moving forward, the emphasis on evidence-based investigations, clinical trials, and international collaboration, particularly involving Chinese researchers, holds promise for advancing understanding and management in this evolving field. In essence, current study provides a nuanced and professionally articulated overview of sepsis and gut microbiome research, paving the way for future exploration and advancements in evidencebased medicine.