Research tendency

A total of 443 articles were selected focusing on gut phage from January 1, 2008, to June 5, 2023. The deadline for article selection was June 2023, and the whole year of publications in 2023 were not complete, so all line charts covered 2008 to 2023 only. Since 2013, the annual number of articles on gut phage had an upward trend, and the number of articles from 2021 to 2022 had the largest increase (Additional file 1: Fig. S2 A).

From January 1, 2008, to June 30, 2023, a total of 630 articles on phage and gut bacteria were selected. In the two periods of 2010–2012 and 2017–2022, the annual number of publications on phage and bacteria showed an increasing trend. Moreover, 2017 is an important time node, as the number of articles in the field decreased in 2016–2017, while the number of articles surged in 2017–2018 (Additional file 1: Fig. S2 B).

Compared with the other two topics, the number of articles on phage and tumor is relatively small from January 1, 2008, to June 21, 2023, with 141 articles. From 2014 to 2019, the number of annual publications on phage and tumor increased steadily. Furthermore, 2020 is also an important time node, because the number of articles declined in 2019–2020, while the number of articles surged in 2020–2021 (Additional file 1: Fig. S2 C).

Collaboration networkGut phage

The articles on gut phage for this study were collected from 59 countries/regions, with a network density of 0.0479 (Fig. 2 A). From 2008 to 2023, the United States of America (USA), China, and France were the most frequent publishers, with 173 (39.05%), 63 (14.22%) and 43 (9.71%) articles, respectively (Table 1). The number of articles in the USA had a significant advantage, with a half-life of 10.5, which indicated that the USA had achieved excellent results in the quantity and quality of articles in the field of gut phage research. Additionally, Switzerland, Canada, USA, etc. tended to conduct collaborative research with other countries/regions. For example, Switzerland had international cooperation with 8 countries/regions, such as Russia, while Canada had international cooperation with 5 countries/regions, such as PRC.

Fig. 2

Cooperative network analysis of gut phage. A Cooperation network map for countries/regions. B Cooperation network map for institutions. C Cooperation network map for authors

Table 1 Top 5 of most productive countries,regions on gut phage

A total of 295 institutions and 436 authors were screened for visual analysis. Harvard University (29 articles), UDICE -French research universities (29 articles), University of California System (28 articles), University College Cork (25 articles), Universite Paris Cite (20 articles) were the top 5 most frequently published institutions (Fig. 2 B). Most institutions were universities. Hill, Colin,Ross (12 articles), R Paul,Shkoporov (10 articles), Andrey N (7 articles), Debarbieux, Laurent (7 articles) were the top 4 most frequently published authors (Fig. 2 C).

Phage and bacteria

A total of 58 countries, including USA, China and Canada, were collected from January 1, 2008, to June 20, 2023 (Fig. 3 A). The USA ranked first with 193 articles (31.64%), followed by China with 92 articles (15.08%), and Canada with 48 articles (7.87%) ranked third. There were 16 important countries/regions with high centrality, including France, Canada, England and USA. Some developed countries, including the USA, Canada, Russia and France, started research earlier and carried out extensive international cooperation. For example, Canada had cooperation with 7 countries/regions, such as Finland, Poland and Chile. In terms of number, centrality and half-life of articles, USA and China occupied a dominant position in the quantity and quality of articles published in this field (Table 2).

Fig. 3

Cooperative network analysis of phage and bacteria. A Cooperation network map for countries/regions. B Cooperation network map for institutions. C Cooperation network map for authors

Table 2 Top 6 of most productive countries/regions on phage and bacteria

There were 331 nodes, 512 connections, and a network density of 0.0094 for institutions (Fig. 3 B). Ten institutions, including The Centre National de la Recherche Scientifique (CNRS), University of California System, and University of Guelph, played an important connecting role in the network of institutional cooperation. Among the 10 institutions in the forefront of annual article production (Table 3), 5 belonged to France (50%), 2 to the USA (20%), 2 to Poland (20%), and 1 to Finland (10%).

Table 3 Top 7 of most productive institutions on phage and bacteria

There were 471 nodes, 475 connections, and a network density of 0.0043 for authors (Fig. 3 C). The productive authors include Wegrzyn Grzegorz, Bloch Sylwia, and Wu Vivian C H, and 14 others with at least 5 articles.

Phage and tumor

Articles on phage and tumor from 36 countries/regions, such as USA and PRC, were collected (Fig. 4 A). The USA held the top spot with 48 articles, followed by PRC with 36 articles and England with 16 articles (Table 4). Notably, the USA had an important influence in the network of national cooperation network, so it played a bridging role. What’s more, based on publication frequency and half-life, USA and China served as trailblazers in the field of phage and tumor research.

Fig. 4

Cooperative network analysis of phage and tumor. A Cooperation network map for countries/regions. B Cooperation network map for institutions. C Cooperation network map for authors

Table 4 Top 5 of most productive countries/regions on phage and tumor

There were 240 nodes, 510 connections, and a network density of 0.0178 for institutions (Fig. 4 B). Among them, a total of 7 institutions, including Imperial College London, Harvard University and Polish Academy of Sciences, published at least 5 articles.

There were 372 nodes, 903 connections, and a network density of 0.0131 for authors (Fig. 4 C). Hajitou Amin was the most productive author with considerable article quality and conducted extensive cooperation with other authors. Hajitou Amin had an early insight into the ability of phages to target tumors, and used them as vectors to deliver tumor necrosis factor, CRISPR-Cas9 transgene boxes, etc., for immunotherapy and gene delivery of various cancers such as melanoma [25, 35, 36].

Reference co-citation and research hotspotGut phage

There were 668 nodes, 1,414 connections, and a network density of 0.0063, and 13 clusters were presented, including #0 eggerthella lenta, #1 virus-bacteria linkages, #2 phage resistance, #3 human gut, #4 phage translocation, #5 vancomycin-resistant enterococcus faecalis, #6 correlation, #7 crassphage, #8 carrier state lifecycle, #9 probiotic bacteria, #10 microbiome, #11 campylobacter jejuni, and #12 symnioses (Fig. 5 A). #9 probiotic bacteria and #11 campylobacter jejuni started early, while #0 eggerthella lenta, #1 virus-bacteria linkages, and #2 phage resistance have received attention in recent years (Fig. 5 B).

Fig. 5

Reference co-citation analysis of gut phage. A Reference clustering map. B Reference co-citation time diagram. C The top 25 co-cited references with the strongest burst intensity

Totally, 6 citations burst starting in 2021 and beyond (Fig. 5 C). These citations explored the phage-dominated viral genome to discover its diversity and individual specificity and investigated potential associations among bacteriome, metabolome, and viriome [37,38,39,40]. For example, the citation (strength = 8.13) by Ann C Gregory et al. described a human enterovirus database (GVB) of 1,986 individuals from 16 countries, which confirmed the individual specificity of phages and revealed the shift in viral diversity from infancy to old age[39].

Phage and bacteria

The top 13 clusters were presented from 740 co-cited articles, including #0 bacteriophage, #1 jumbo phage, #2 shiga toxin, #3 feces, #4 human gut microbiome, #5 bacteriophage t4, #6 d6, #7 virulence, #8 h7, #9 genome analysis, #10 microbiota, #11 diarrhea, and #12 peptidoglycan hydrolase (Fig. 6 A). Among them, #1 jumbo phage, #4 human gut microbiome, #7 virulence, and #8 h7 were expected to attract more investment in future research. Additionally, #0 e. coli o157:h7 and #5 bacteriophage t4 started early with relatively profound research foundation (Fig. 6 B).

Fig. 6

Reference co-citation analysis of phage and bacteria. A Reference clustering map. B Reference co-citation time diagram. C The top 25 co-cited references with the strongest burst intensity

The timeline of the top 25 co-cited articles on phage and bacteria with the strongest bursts was shown in Fig. 6 C. The citation written by Alejandro Reyes et al. had the strongest burst strength (6.45) and focused on the concept of gut virome early [41]. Articles that might reveal the potential future research hotspots (burst end = 2023) mainly concentrated on the further exploration and application of phage properties. First, the current research on the characteristics of phages seemed to be more focused on the study of its survival mechanism and comparison between individuals, including its mechanism of targeting host and avoiding attack [42, 43], as well as the high individual specificity of the phage-dominated virome [37], which provides the premise of multi-disciplinary application of phages. Besides, based on the impacts of phage on gut bacteria and even gut microbiome, the application of phages was expected to attract more attention, such as the treatment of bacterial infection and food safety problems [44,45,46].

Phage and tumor

There were 465 nodes, 1,199 connections, and a network density of 0.0111 for citation on phage and tumor (Fig. 7 A). The top 13 clusters included #0 esophageal diseases, #1 ge11, #2 melanoma, #3 temozolomide, #4 crispr-cas9, #5 nanoparticle, #6 cec, #7 coli phagelysate, #8 combined therapy, #9 aptamers, #10 hpv vaccine, #11 immune checkpoint inhibitor, and #12 collagen. #2 melanoma, #3 temozolomide, #8 combined therapy, and #9 aptamers started early with a relatively in-depth study while #5 nanoparticle and #7 coli phagelysate appeared recently and could be the focus of the future research (Fig. 7 B).

Fig. 7

Reference co-citation analysis of phage and tumor. A Reference clustering map. B Reference co-citation time diagram. C The top 25 co-cited references with the strongest burst intensity

A total of 7 citation burst started in 2021 and lasted until the search deadline, which had a certain directional effect on future research hotspots (Fig. 7 C). The potential of phages in the diagnosis and treatment of cancer such as CRC has been emphasized, and the changes of intestinal mucosa have been revealed to be related to phages [5, 10, 16, 47,48,49]. For example, the citation by Lasha Gogokhia et al. (strength = 2.11) revealed that phages promoted mucosal IFN-γ through a TLR9-dependent pathway, which enhanced mucosal immunity and exacerbated the occurrence of colitis [10]. Rebekah M. Dedrick et al. reported for the first time a case study (strength = 2.07) of the use of engineered phages in human treatment of drug-resistant mycobacterium abscess with clinical improvements such as liver function recovery, which strongly suggested the potential of effective combination of phage and genetic engineering technology in clinical practice [49].

Keyword co-occurrence and burstGut phage

The top 13 clusters were presented from 394 keyword nodes (Q = 0.7519), including #0 phageome, #1 community, #2 antibiotic reststance, #3 dynamics, #4 enterococcus, #5 shiga toxin, #6 escherichia coli, #7 volunteers, #8 ulcerative colitis, #9 capsid proteins, #10 alignment, #11 in vitro, and #12 animal models (Fig. 8 A).

Fig. 8

Keyword analysis of gut phage. A Keyword clustering map. B Keyword time diagram. C The top 25 keywords with the strongest burst intensity

Some keywords, such as “escherichia coli”, “identification” and “therapy”, appeared early, while others, such as “gut virome”, emerged in recent years (Fig. 8 B). The top 25 keywords with the strongest citation bursts were presented in Fig. 8 C. “Phage therapy” (strength = 3.46), “viral community” (strength = 3.76), “infection” (strength = 3.19), etc. were the hot spots of early research, while “gut microbiome” (strength = 2.94), “database” (strength = 3.83), “microbiota” (strength = 3.12), “expansion” (strength = 2.89), and “mice” (strength = 2.18) would be the future research hot spots.

Phage and bacteria

The top 13 clusters were presented from 413 keyword nodes (Q = 0.6972), including #0 operon, #1 antimicrobial resistance, #2 phage therapy, #3 rna polymerase, #4 shiga toxin, #5 bacteriophage t4, #6 biocontrol, #7 outbreak, #8 gut microbiota, #9 escherichia coli, #10 mutants, #11 antagonistic coevolution, and #12 mung bean seeds (Fig. 9 A). “Escherichia coli” had the highest frequency of 177, ranking the first keyword, followed by identification with a frequency of 81, and “bacteriophage” and “phage” with a frequency of 61.

Fig. 9

Keyword analysis of phage and bacteria. A Keyword clustering map. B Keyword time diagram. C The top 25 keywords with the strongest burst intensity

Moreover, “escherichia coli”, “identification”, “protein”, “phage”, etc. were the earliest hotspot keywords since 2008, while “antimicrobial resistance (amr)”, “stability” and “1st step transfer dna” had emerged recently (Fig. 9 B). Among the keywords of high burst intensity, the keywords of burst beginning in 2021 or later were noticed, including “alignment” (strength = 2.93), “lipopolysaccharide” (strength = 2.6), “microbiota” (strength = 2.4), “human gut” (strength = 2.34), “escherichia coli 0157” (strength = 2.34), and “gut microbiota” (strength = 2.93) (Fig. 9 C).

Phage and tumor

There were 322 keyword nodes in total, and 13 clusters are presented (Q = 0.7077) including #0 gene therapy, #1 hpv vaccine, #2 virome, #3 short-wavelength infrared imaging, #4 cancer, #5 cancer gene therapy, #6 nanoparticle, #7 m13 bacteriophage, #8 carbohydrates, #9 biomaterials, #10 microbial network, #11 phage idiotype vaccination, and #12 immune checkpoint inhibitor (Fig. 10 A).

Fig. 10

Keyword analysis of phage and tumor. A Keyword clustering map. B Keyword time diagram. C The top 25 keywords with the strongest burst intensity

Key words, including “delivery” (frequency = 19), “cancer” (frequency = 19), “expression” (frequency = 17), “cells” (frequency = 15), “therapy” (frequency = 12) and “colorectal cancer” (frequency = 18), had deep research foundation, and still are the topic of the current study (Fig. 10 B). Among the keywords with high burst intensity with the burst start time of 2021 and beyond, “colorectal cancer” (strength = 3.7) ranked first, followed by “proteins” (strength = 2.84) and “phage therapy” (strength = 3.7) (Fig. 10 C).