Gut Pathogens

Rezasoltani, Sama; Azizmohammad Looha, Mehdi; Asadzadeh Aghdaei, Hamid; Jasemi, Seyedesomayeh; Sechi, Leonardo Antonio; Gazouli, Maria; Sadeghi, Amir; Torkashvand, Shirin; Baniali, Reyhaneh; Schlüter, Hartmut; Zali, Mohammad Reza; Feizabadi, Mohammad Mehdi

2024 Gut Pathogens

doi: 10.1186/s13099-024-00604-0pmid: 38378690

BackgroundColorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening utilizing innovative biomarkers, is pivotal for mitigating CRC incidence. This study aims to scrutinize the fecal and salivary microbiomes of CRC-positive individuals (CPs) in comparison to CRC-negative counterparts (CNs) to enhance early CRC diagnosis through microbial biomarkers.Material and methodsA total of 80 oral and stool samples were collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, encompassing both CPs and CNs undergoing screening. Microbial profiling was conducted using 16S rRNA sequencing assays, employing the Nextera XT Index Kit on an Illumina NovaSeq platform.ResultsDistinct microbial profiles were observed in saliva and stool samples of CPs, diverging significantly from those of CNs at various taxonomic levels, including phylum, family, and species. Saliva samples from CPs exhibited abundance of Calothrix parietina, Granulicatella adiacens, Rothia dentocariosa, and Rothia mucilaginosa, absent in CNs. Additionally, Lachnospiraceae and Prevotellaceae were markedly higher in CPs' feces, while the Fusobacteria phylum was significantly elevated in CPs' saliva. Conversely, the non-pathogenic bacterium Akkermansia muciniphila exhibited a significant decrease in CPs' fecal samples compared to CNs.ConclusionThrough meticulous selection of saliva and stool microbes based on Mean Decrease GINI values and employing logistic regression for saliva and support vector machine models for stool, we successfully developed a microbiota test with heightened sensitivity and specificity for early CRC detection.

Wang, Sui; Kou, Guan-Jun; Zhao, Xiao-Han; Huang, Gang; Wang, Jue-Xin; Tian, Lin; Zuo, Xiu-Li; Li, Yan-Qing; Wang, Jia-Yong; Yu, Yan-Bo

2024 Gut Pathogens

doi: 10.1186/s13099-024-00617-9pmid: 38678229

BackgroundPeutz–Jeghers syndrome (PJS) is a rare genetic disorder characterized by the development of pigmented spots, gastrointestinal polyps and increased susceptibility to cancers. Currently, most studies have investigated intestinal microbiota through fecal microbiota, and there are few reports about mucosa-associated microbiota. It remains valuable to search for the key intestinal microbiota or abnormal metabolic pathways linked to PJS.AimThis study aimed to assess the structure and composition of mucosa-associated microbiota in patients with PJS and to explore the potential influence of intestinal microbiota disorders and metabolite changes on PJS.MethodsThe bacterial composition was analyzed in 13 PJS patients and 12 controls using 16S rRNA gene sequencing (Illumina MiSeq) for bacteria. Differential analyses of the intestinal microbiota were performed from the phylum to species level. Liquid chromatography-tandem mass spectrometry (LC‒MS) was used to detect the differentially abundant metabolites of PJS patients and controls to identify different metabolites and metabolic biomarkers of small intestinal mucosa samples.ResultsHigh-throughput sequencing confirmed the special characteristics and biodiversity of the mucosa microflora in patients with PJS. They had lower bacterial biodiversity than controls. The abundance of intestinal mucosal microflora was significantly lower than that of fecal microflora. In addition, lipid metabolism, amino acid metabolism, carbohydrate metabolism, nucleotide metabolism and other pathways were significantly different from those of controls, which were associated with the development of the enteric nervous system, intestinal inflammation and development of tumors.ConclusionThis is the first report on the mucosa-associated microbiota and metabolite profile of subjects with PJS, which may be meaningful to provide a structural basis for further research on intestinal microecology in PJS.

Mo, Chunyan; Lou, Xiran; Xue, Jinfang; Shi, Zhuange; Zhao, Yifang; Wang, Fuping; Chen, Guobing

2024 Gut Pathogens

doi: 10.1186/s13099-024-00635-7pmid: 39097746

Intestinal barriers play a crucial role in human physiology, both in homeostatic and pathological conditions. Disruption of the intestinal barrier is a significant factor in the pathogenesis of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. The profound influence of the gut microbiota on intestinal diseases has sparked considerable interest in manipulating it through dietary interventions, probiotics, and fecal microbiota transplantation as potential approaches to enhance the integrity of the intestinal barrier. Numerous studies have underscored the protective effects of specific microbiota and their associated metabolites. In recent years, an increasing body of research has demonstrated that Akkermansia muciniphila (A. muciniphila, Am) plays a beneficial role in various diseases, including diabetes, obesity, aging, cancer, and metabolic syndrome. It is gaining popularity as a regulator that influences the intestinal flora and intestinal barrier and is recognized as a ‘new generation of probiotics’. Consequently, it may represent a potential target and promising therapy option for intestinal diseases. This article systematically summarizes the role of Am in the gut. Specifically, we carefully discuss key scientific issues that need resolution in the future regarding beneficial bacteria represented by Am, which may provide insights for the application of drugs targeting Am in clinical treatment.

Kot, Karolina; Michaliszyn, Adam; Kalisińska, Elżbieta; Lepczyńska, Małgorzata

2024 Gut Pathogens

doi: 10.1186/s13099-024-00613-zpmid: 38570865

Blastocystis sp. is one of the most frequently detected protozoa during stool specimen examination. In the last decade, the studies about the pathogenic potential of Blastocystis sp. have intensified. Additionally, treatment approaches against this parasite are still disputable. The study aimed to investigate the in vitro activity of the substances of natural origin against two subtypes (ST) of Blastocystis sp.—ST3 and ST7. Garlic and turmeric extracts exhibited the highest inhibitory effect in relation to the ST3 viability. While horseradish and turmeric were found to be the most effective extracts to the ST7 viability. The study showed that ginger, garlic, horseradish, and turmeric extracts have potent antimicrobial activity against Blastocystis ST3 and ST7, with the half-maximal inhibitory concentration (IC50) ranging from 3.8 to 4.8 µg/ml and from 3.3 to 72.0 µg/ml, respectively, and thus may be useful in the prevention and control of Blastocystis infections. Additionally, this research confirmed that Blastocystis ST7 is more resistant to the selected plant extracts treatment than Blastocystis ST3 which in consequence may bring some difficulties in its eradication.

Dovrolis, Nikolas; Gazouli, Maria; Rigal, François; Whittaker, Robert J.; Matthews, Thomas J.; Georgiou, Konstantinos; Theodoropoulos, George; Triantis, Kostas A.

2024 Gut Pathogens

doi: 10.1186/s13099-024-00631-xpmid: 38972996

It has recently been proposed that the study of microbial dynamics in humans may gain insights from island biogeographical theory. Here, we test whether the diversity of the intratumoral microbiota of colorectal cancer tumors (CRC) follows a power law with tumor size akin to the island species-area relationship. We confirm a direct correlation between the quantity of Amplicon Sequence Variants (ASVs) within CRC tumors and tumor sizes, following a (log)power model, explaining 47% of the variation. Understanding the processes involved, potentially through the analogy of tumors and islands, may ultimately contribute to future clinical and therapeutic strategies.

Varghese, Tintu; Mills, James A. Platts; Revathi, R.; Antoni, Sebastien; Soeters, Heidi M.; Emmanuel Njambe, Tondo Opute; Houpt, Eric R.; Tate, Jacqueline E.; Parashar, Umesh D.; Kang, Gagandeep

2024 Gut Pathogens

doi: 10.1186/s13099-024-00599-8pmid: 38600552

Malnourished children are at higher risk of mortality and morbidity following diarrheal illness and certain enteropathogens have been associated with malnutrition in children. Very few studies have comprehensively looked at the etiology of diarrhea in malnourished children and most have used conventional diagnostic methods with suboptimal sensitivity. We used a highly sensitive molecular approach against a broad range of pathogens causing diarrhea and examined their association with malnutrition. In addition, we looked at the pathogen diversity of pediatric diarrhea, three years after the nationwide rotavirus vaccine introduction to understand the evolving landscape of pathogens, which is crucial for planning strategies to further reduce the diarrhea burden. Clinical details and diarrheal stool samples were collected from hospitalized children aged < 5 years from three sentinel sites in India for a period of one year. The samples were tested by qPCR for 16 established causes of diarrhea using TaqMan Array Cards. A total of 772 children were enrolled, from whom 482 (62.4%) stool specimens were tested. No specific pathogen was associated with diarrhea among children with acute or chronic malnutrition compared to those with better nutritional status. Overall, adenovirus was the leading pathogen (attributable fraction (AF) 16.9%; 95% CI 14.1 to 19.2) followed by rotavirus (AF 12.6%; 95% CI 11.8 to 13.1) and Shigella (AF 10.9%; 95% CI 8.4 to 16.4). The majority of diarrhea requiring hospitalization in children aged < 2 years could be attributed to viruses, while Shigella was the most common pathogen among children aged > 2 years. These data on the prevalence and epidemiology of enteropathogens identified potential pathogens for public health interventions.

Mannstadt, Insa; Choy, Alexa M.; Li, Jianhua; Green, Daniel A.; Freedberg, Daniel E.

2024 Gut Pathogens

doi: 10.1186/s13099-024-00638-4pmid: 39215373

BackgroundThe use of gastrointestinal disease multiplex polymerase chain reaction (GI PCR) testing has become common for suspected gastrointestinal infection. Patients often test positive for multiple pathogens simultaneously through GI PCR, although the clinical significance of this is uncertain.MethodsThis retrospective cohort study investigated risk factors and clinical outcomes associated with detection of multiple (as opposed to single) pathogens on GI PCR. We included adult patients who underwent GI PCR testing from 2020 to 2023 and had one or more pathogens detected. We compared patients with multiple versus those with single pathogens and hypothesized that immunosuppression would be a risk factor for detection of multiple pathogens. We further hypothesized that, during the 90 days after GI PCR testing, patients with multiple pathogens would have worse clinical outcomes such as increased rates of emergency department (ED) visits, death, hospitalization, or ambulatory care visits.ResultsGI PCR was positive in 1341 (29%) of tested patients; 356 patients had multiple pathogens and 985 had one pathogen. The most common pathogens included Enteropathogenic Escherichia coli (EPEC, 27%), norovirus (17%), and Enteroaggregative E. coli (EAEC, 14%) in both multi- and singly positive patients. Immunosuppression was not associated with multiple pathogens (adjusted odds ratio [aOR] 1.35, 95% CI 0.96, 1.86). The factors most associated with multiple pathogens were Hispanic ethnicity (OR 1.86, 95% CI 1.42, 2.45) and chronic kidney disease (OR 1.69, 95% CI 1.13, 2.49). Patients with multiple pathogens were more likely to have ED visits during the 90 days after GI PCR testing (40% vs. 32%, p < 0.01), but they were not more likely to die, be hospitalized, or to have ambulatory medical visits.ConclusionsImmunosuppression was not associated with detection of multiple as opposed to single pathogens on GI PCR testing. There were worse clinical outcomes associated with detection of multiple pathogens, although these effects were modest.

Abdoli, Amir; Olfatifar, Meysam; Eslahi, Aida Vafae; Moghadamizad, Zeinab; Samimi, Rasoul; Habibi, Mohammad Amin; Kianimoghadam, Amir Sam; Badri, Milad; Karanis, Panagiotis

2024 Gut Pathogens

doi: 10.1186/s13099-024-00602-2pmid: 38282036

BackgroundPatients with mental disorders have a high risk of intestinal parasitic infection due to poor hygiene practices. Hence, to better clarify this overlooked phenomenon, the current study is conducted to determine the global prevalence of protozoan parasite infections in patients with mental disorders and investigate the associated risk factors.MethodsSeveral databases (PubMed, Scopus, Web of Science, ProQuest, and Google Scholar) were searched for papers published until December 2022. The fixed effect meta-analysis was used to estimate the overall odds ratio (OR) and pooled prevalence was estimated using a random-effects model with a 95% confidence interval (CI).ResultsTotally, 131 articles (91 case–control and 40 cross-sectional studies) met the eligibility criteria. Patients with mental disorders were significantly at higher risk for protozoan parasites than healthy controls (OR: 2.059, 1.830–2.317). The highest pooled OR (2.485, 1.413–4.368) was related to patients with neurodevelopmental disorders, and the highest pooled prevalence was detected in patients with neurodevelopmental disorders (0.341, 0.244–0.446), followed by bipolar and related disorders (0.321, 0.000–0.995). Toxoplasma gondii was the most prevalent protozoan parasite (0.343, 0.228–0.467) in cross-sectional studies and the highest pooled OR was related to Cyclospora cayetanensis (4.719, 1.352–16.474) followed by Cryptosporidium parvum (4.618, 2.877–7.412).ConclusionOur findings demonstrated that individuals afflicted with mental disorders are significantly more susceptible to acquiring protozoan parasites in comparison to healthy individuals. Preventive interventions, regular screening, and treatment approaches for parasitic diseases should be considered for patients with mental disorders.

Wang, Kuan-Chieh; Chu, Chun-Hao; Chiang, Che-Ming; Zeng, Fu-Ruei; Huang, Ching-Wen; Lin, Chien-Ming

2024 Gut Pathogens

doi: 10.1186/s13099-024-00621-zpmid: 38824586

BackgroundIntussusception, a common cause of abdominal pain in children, often lacks clear underlying causes and is mostly idiopathic. Recurrence, though rare, raises clinical concerns, with rates escalating after each episode. Factors like pathological lead points and Henoch-Schönlein purpura (HSP) are associated with recurrent cases. On the other hand, the prevalence of Helicobacter pylori (H. pylori), often asymptomatic, in children has been declining. Although its infection is reported to be linked with HSP, its role in recurrent intussusception remains unexplored. Further research is needed to understand the interplay among H. pylori (culprit pathogen), HSP (trigger), and intractable intussusception so as to develop effective management strategies.Case presentationA two-year-old girl experienced four atypical episodes of intussusception at distinct locations, which later coincided with HSP. Despite treatment with steroids, recurrent intussusception persisted, suggesting that HSP itself was not a major cause for intractable presentations. Subsequent identification of H. pylori infection and treatment with triple therapy resulted in complete resolution of her recalcitrant intussusception.ConclusionThis instructive case underscored a sequence wherein H. pylori infection triggered HSP, subsequently resulting in recurrent intussusception. While H. pylori infection is not common in young children, the coexistence of intractable intussusception and steroid-resistant recurrent HSP necessitates consideration of H. pylori infection as a potential underlying pathogen.

Huang, Guoxin; Zheng, Yilin; Zhang, Ni; Huang, Guohai; Zhang, Weijin; Li, Qingnan; Ren, Xuecong

2024 Gut Pathogens

doi: 10.1186/s13099-024-00632-wpmid: 39060944

BackgroundSulfate-reducing bacteria (SRB) is a potential pathogen usually detected in patients with gastrointestinal diseases. Hydrogen sulfide (H2S), a metabolic byproduct of SRB, was considered the main causative agent that disrupted the morphology and function of gut epithelial cells. Associated study also showed that flagellin from Desulfovibrio vulgaris (DVF), the representative bacterium of the Desulfovibrio genus, could exacerbate colitis due to the interaction of DVF and LRRC19, leading to the secretion of pro-inflammatory cytokines. However, we still have limited understanding about the change of gut microbiota (GM) composition caused by overgrowth of SRB and its exacerbating effects on colitis.ResultsIn this study, we transplanted D. vulgaris into the mice treated with or without DSS, and set a one-week recovery period to investigate the impact of D. vulgaris on the mice model. The outcomes showed that transplanted D. vulgaris into the normal mice could cause the gut inflammation, disrupt gut barrier and reduce the level of short-chain fatty acids (SCFAs). Moreover, D. vulgaris also significantly augmented DSS-induced colitis by exacerbating the damage of gut barrier and the secretion of inflammatory cytokines, for instance, IL-1β, iNOS, and TNF-α. Furthermore, results also showed that D. vulgaris could markedly change GM composition, especially decrease the relative abundance of SCFAs-producing bacteria. Additionally, D. vulgaris significantly stimulated the growth of Akkermansia muciniphila probably via its metabolic byproduct, H2S, in vivo.ConclusionsCollectively, this study indicated that transplantation of D. vulgaris could cause gut inflammation and aggravate the colitis induced by DSS.