Microbiology

Article Gastroenterology & Hepatology

Allogeneic hematopoietic cell transplantation, the microbiome, and graft-versus-host disease

Yannouck F. van Lier, Jael Vos, Bianca Blom, Mette D. Hazenberg

Summary: Patients with hematological malignancies often undergo allogeneic hematopoietic cell transplantation (HCT) to cure their condition. HCT can disrupt the intestinal microbiota, leading to poor transplant outcomes and graft-versus-host disease (GvHD). Strategies such as dietary interventions, antibiotic stewardship, and fecal microbiota transplantation are being explored to prevent or treat microbiota injury and GvHD. This review provides insights into the role of microbiome in GvHD pathogenesis and summarizes interventions for microbiota injury prevention and treatment.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Kinetic and mechanistic diversity of intestinal immune homeostasis characterized by rapid removal of gut bacteria

Da-Jung Jung, Ledia Gebremedhin, Byoungsook Goh, Ji-Sun Yoo, Francesca Gazzaniga, Dennis L. Kasper, Sungwhan F. Oh

Summary: Symbiotic microbiota play a critical role in maintaining host immune homeostasis in a cell-specific manner. Germ-free animals have been the gold standard for excluding microbial components but complete removal of gut microbiota from birth can impair physiological development. Using an improved regimen, we were able to rapidly remove gut microbiota and maintain sterility in animals without any adverse reactions. This method allowed us to observe kinetic differences among colonic lymphocyte subsets that are not observed in traditional germ-free animal models. Additionally, we were able to distinguish between direct stimulation and homeostatic cues of microbiota contribution to effector cell function.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Shorter sleep time relates to lower human defensin 5 secretion and compositional disturbance of the intestinal microbiota accompanied by decreased short-chain fatty acid production

Yu Shimizu, Ryodai Yamamura, Yuki Yokoi, Tokiyoshi Ayabe, Shigekazu Ukawa, Koshi Nakamura, Emiko Okada, Akihiro Imae, Takafumi Nakagawa, Akiko Tamakoshi, Kiminori Nakamura

Summary: Sleep is crucial for our health, and insufficient sleep can increase the risk of diseases due to imbalanced intestinal microbiota. However, the mechanisms through which short sleep leads to dysbiosis remain unknown. This study aims to investigate the effects of short sleep on HD5 secretion and the intestinal microbiota.

GUT MICROBES (2023)

Review Gastroenterology & Hepatology

Succinate metabolism and its regulation of host-microbe interactions

Yi-han Wei, Xi Ma, Jiang-Chao Zhao, Xiu-Qi Wang, Chun-Qi Gao

Summary: This review focuses on the role of succinate, a metabolite produced by both host cells and gut microbes, in activating intestinal mucosal cells and regulating the gut-immune tissue axis. It also explores its function as a mediator of microbiota-host crosstalk and its potential in regulating intestinal microbiota homeostasis. The review provides insights into feasible ways to modulate succinate levels and highlights succinate as a potential target for microbial therapeutics for humans.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Microbial metabolites in colorectal tumorigenesis and cancer therapy

Yali Liu, Harry Cheuk-Hay Lau, Jun Yu

Summary: Trillions of microbes in the human gastrointestinal tract form an ecological community known as the gut microbiota, which plays a crucial role in dietary digestion and produces various metabolites. However, these microbial metabolites have been found to be correlated with the development of colorectal cancer (CRC) and can also impact the efficacy of cancer treatments. This review discusses the role of metabolites derived from microbes-mediated metabolism of dietary components and their influence on CRC development, as well as their impacts on chemotherapy and immunotherapy. Targeting metabolites may be a promising therapeutic approach for improving patient outcome in CRC.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Limosilactobacillus reuteri normalizes blood-brain barrier dysfunction and neurodevelopment deficits associated with prenatal exposure to lipopolysaccharide

Jing Lu, Xiaobing Fan, Lei Lu, Yueyue Yu, Erica Markiewicz, Jessica C. Little, Ashley M. Sidebottom, Erika C. Claud

Summary: Maternal immune activation (MIA) derived from late gestational infection increases the risk of neurodevelopmental deficits in offspring. This study shows that MIA induced underdevelopment and dysfunction of the blood-brain barrier (BBB) in prewean mice, leading to impaired spatial learning later in life. Maternal supplementation of Limosilactobacillus reuteri (L. reuteri) rescued BBB development and cognitive function associated with BBB dysfunction.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Machine learning model for predicting age in healthy individuals using age-related gut microbes and urine metabolites

Seung-Ho Seo, Chang-Su Na, Seong-Eun Park, Eun-Ju Kim, Woo-Seok Kim, ChunKyun Park, Seungmi Oh, Yanghee You, Mee-Hyun Lee, Kwang-Moon Cho, Sun Jae Kwon, Tae Woong Whon, Seong Woon Roh, Hong-Seok Son

Summary: Age-related changes in gut microbes and urine metabolites were studied in 568 healthy individuals. The richness and evenness of fecal microbiota increased with age, and 16 genera showed significant abundance differences between young and old groups. Additionally, 17 urine metabolites contributed to the age-related differences. Bacteroides and Prevotella 9 were found to be correlated with some urine metabolites. The machine learning algorithm XGBoost achieved the best age prediction performance, with a mean absolute error of 5.48 years. Including urine metabolite data improved the accuracy to 4.93 years. This study highlights the potential of using gut microbiota and urine metabolic profiles for age prediction in healthy individuals.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

The claim of primacy of human gut Bacteroides ovatus in dietary cellobiose degradation

Meixia Li, Yeqing Wang, Ciliang Guo, Sheng Wang, Liangzhen Zheng, Yifan Bu, Kan Ding

Summary: A demonstration of cellulose degrading bacterium from human gut challenged the belief that humans cannot degrade cellulose. However, research on the molecular level of cellulose degradation by human gut microbiota is still incomplete. Using cellobiose as a model, we investigated the molecular mechanism behind cellulose degradation by key members of the human gut microbiota, such as Bacteroides ovatus (BO). Our results showed that a new polysaccharide utilization locus (PUL) from BO was involved in cellobiose capturing and degradation, and two new cellulases on the cell surface, BACOVA_02626 (GH5) and BACOVA_02630 (GH5), were responsible for cellobiose degradation into glucose. Studies on mice also revealed that cellobiose reshaped the gut microbiota composition and potentially modified bacterial metabolic functions. These findings provide further evidence of cellulose degradation by human gut microbes and contribute new insights to cellulose research.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes

Laila Silamikele, Rihards Saksis, Ivars Silamikelis, Patricija Pauline Kotovica, Monta Briviba, Ineta Kalnina, Zane Kalnina, Davids Fridmanis, Janis Klovins

Summary: This study investigated the spatial variation of the gut microbiome in a mouse model of type 2 diabetes induced by a high-fat diet. The results showed that metformin treatment significantly altered the gut microbiome diversity in different intestinal parts, with the most pronounced effect in the small intestine. The abundance of Lactococcus increased remarkably, while the abundance of Lactobacillus was lower in male mice compared to female mice. Diet type and intestinal layer also had significant effects on microbiome composition.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Crohn's disease proteolytic microbiota enhances inflammation through PAR2 pathway in gnotobiotic mice

Alba Santiago, Amber Hann, Marco Constante, Sara Rahmani, Josie Libertucci, Kyle Jackson, Gaston Rueda, Laura Rossi, Ramachandran Rithwick, Wolfram Ruf, Jon Schertzer, Alberto Caminero, Premysl Bercik, Heather Jean Galipeau, Elena Francisca Verdu

Summary: Emerging evidence suggests that microbial proteolytic activity is implicated in ulcerative colitis (UC), but its role in Crohn's disease (CD) remains unclear. This study investigated the effects of colonizing germ-free mice with CD microbiota and healthy control microbiota. It was found that CD proteolytic microbiota increased colitis severity through a PAR2 pathway. These findings highlight the proinflammatory nature of CD proteolytic microbiota and its role in exacerbating colitis.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Epithelial talin-1 protects mice from citrobacter rodentium-induced colitis by restricting bacterial crypt intrusion and enhancing t cell immunity

Yvonne L. L. Latour, Margaret M. M. Allaman, Daniel P. P. Barry, Thaddeus M. M. Smith, Kamery J. J. Williams, Kara M. M. McNamara, Justin Jacobse, Jeremy A. A. Goettel, Alberto G. G. Delgado, M. Blanca Piazuelo, Shilin Zhao, Alain P. P. Gobert, Keith T. T. Wilson

Summary: Lack of talin-1 in intestinal epithelial cells increases susceptibility to colonic disease caused by pathogenic Escherichia coli, leading to decreased survival, increased colonization, colon weight, and histologic colitis. Loss of talin-1 in colonic epithelial cells impairs recruitment and activation of T cells, exacerbating colonic mucosal hyperplasia and cell crowding in the glands.

GUT MICROBES (2023)

Review Gastroenterology & Hepatology

The emerging role of the gut mycobiome in liver diseases

Natalia Szostak, Marek Figlerowicz, Anna Philips

Summary: In recent years, the role of gut microbiota in human health and disease has gained increasing attention. However, most studies on the gut microbiome primarily focus on bacteria and neglect the fungi that exist in the human intestines. This review highlights the importance of the gut mycobiome in liver homeostasis and its perturbations, emphasizing the compositional changes of fungi in liver diseases and providing new insights for liver research and potential therapeutic targets.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Genome-wide multi-omics analysis reveals the nutrient-dependent metabolic features of mucin-degrading gut bacteria

Kyoung Su Kim, Eunike Tiffany, Ji-Young Lee, Ara Oh, Hyeon-Su Jin, Ji-Sun Kim, Jung-Sook Lee, Myung Hee Nam, Soo-Jong Hong, Sowon Park, Hong Koh, Bong-Soo Kim, Yun Kyung Lee, Dong-Woo Lee

Summary: In this study, the functional modules of mucin catabolism were assessed through bioinformatics-aided functional annotation. The metabolic pathways of A. muciniphila and R. gnavus were identified and their distinct metabolic features were found to influence the host immune response and gut ecosystem.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Using fecal immmunochemical cartridges for gut microbiome analysis within a colorectal cancer screening program

Stefanie Brezina, Martin Borkovec, Andreas Baierl, Fabienne Bastian, Andreas Futschik, Nikolaus Gasche, Thomas Gruenberger, Michael Hallas, Christian Jannsen, Gernot Leeb, Rebecca Lutz, Barbara Sladek, Andrea Gsur

Summary: The study evaluated the usability of FIT cartridges for microbiome analysis and compared it to Stool Collection and Preservation Tubes. The FIT and Preservation Tube samples had highly similar microbiome profiles, with minor differences between abundances of some bacterial taxa. The results indicate that FIT cartridges are suitable for gut microbiome analysis within CRC screening programs.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Delay in loop ileostomy reversal surgery does not impact upon post-operative clinical outcomes. Complications are associated with an increased loss of microflora in the defunctioned intestine

Emma L. Beamish, Judith Johnson, Barbara Shih, Rebecca Killick, Frank Dondelinger, Ciarra McGoran, Caitlan Brewster-Craig, Albert Davies, Arnab Bhowmick, Rachael J. Rigby

Summary: Loop ileostomy is a common surgical procedure for downstream tissue healing, but the reversal procedure is associated with substantial morbidity. This study investigated the potential influence of delaying ileostomy reversal surgery on clinical and pathological outcomes. The results showed that the length of time a stoma is in place does not impact the likelihood of complications. Microbiota diversity in the functional and defunctioned limb correlated within an individual and was not significantly different between those who experienced complications and those who didn't. Restoring intestinal microbiota numbers prior to reversal surgery may improve clinical outcomes.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Actively replicating gut bacteria identified by 5-ethynyl-2'-deoxyuridine (EdU) click chemistry and cell sorting

Eve T. T. Beauchemin, Claire Hunter, Corinne F. F. Maurice

Summary: The composition of the gut bacterial community is well studied, but the metabolism and replication of these bacteria are not fully understood. In this study, the researchers developed a technique called EdU-click and FACSeq to identify actively replicating gut bacteria. They tested this technique on human gut bacterial isolates and mouse fecal bacteria, and found that certain bacteria, such as Prevotella UCG-001 and Ileibacterium, were enriched in the replicating fraction. They also demonstrated the application of this technique in studying the replication dynamics of gut bacteria exposed to antibiotics. Overall, this technique provides a valuable tool for studying the replication and abundance of gut bacteria in various ecological states.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Fecal virome transfer improves proliferation of commensal gut Akkermansia muciniphila and unexpectedly enhances the fertility rate in laboratory mice

Torben Solbeck Rasmussen, Caroline M. Junker Mentzel, Malene Refslund Danielsen, Rasmus Riemer Jakobsen, Line Sidsel Fisker Zachariassen, Josue Leonardo Castro Mejia, Anders Brunse, Lars Hestbjerg Hansen, Camilla Hartmann Friis Hansen, Axel Kornerup Hansen, Dennis Sandris Nielsen

Summary: This study investigates the use of fecal virome transplantation (FVT) to alter the gut microbiome composition and promote the colonization of conventional probiotics (LGG) and next-generation probiotics (AKM). The results show that FVT did not increase the abundance of these probiotics, but significantly increased the abundance of naturally occurring Akkermansia muciniphila in the gut. Additionally, the FVT-treated mice had a significantly higher fertility rate, suggesting a potential link between the gut microbiome and fertility.

GUT MICROBES (2023)

Review Gastroenterology & Hepatology

Gut microbiota: a non-target victim of pesticide-induced toxicity

Tusha Sharma, Nagabhishek Sirpu Natesh, Ramesh Pothuraju, Surinder K. Batra, Satyanarayana Rachagani

Summary: The human gut microbiota can be disrupted by environmental contaminants such as pesticides, posing potential health risks. The metabolites produced by gut microbiota play a significant role in maintaining host health, and an imbalance in this system can lead to various diseases. Recent studies have shown that pesticides have harmful effects on the host's gut microbiota. Therefore, further research is needed to understand the impact of pesticides on gut microbiota-mediated metabolic changes, which may provide insights into pesticide-induced toxicity.

GUT MICROBES (2023)

Article Gastroenterology & Hepatology

Gut microbiota in nonalcoholic fatty liver disease: a PREDIMED-Plus trial sub analysis

Ana Maria Gomez-Perez, Patricia Ruiz-Limon, Jordi Salas-Salvado, Jesus Vioque, Dolores Corella, Montse Fito, Josep Vidal, Alessandro Atzeni, Laura Torres-Collado, Andrea Alvarez-Sala, Maria Angeles Martinez, Albert Goday, David Benaiges, Jesus Garcia-Gavilan, Maria Rosa Bernal Lopez, Isabel Moreno-Indias, Francisco J. Tinahones

Summary: This study found that the Mediterranean diet and physical activity can change the scores for liver steatosis and liver fibrosis within one year, and these changes are related to changes in gut microbiota. The findings are important for identifying microbiota-based biomarkers for NAFLD and developing strategies to modulate gut microbiota in the treatment of NAFLD.

GUT MICROBES (2023)

Article Immunology

Rational development of multicomponent mRNA vaccine candidates against mpox

Rong-Rong Zhang, Zheng-Jian Wang, Yi-Long Zhu, Wei Tang, Chao Zhou, Suo-Qun Zhao, Mei Wu, Tao Ming, Yong-Qiang Deng, Qi Chen, Ning-Yi Jin, Qing Ye, Xiao Li, Cheng-Feng Qin

Summary: The re-emerging mpox virus has become a public health emergency of international concern and developing a safe and effective mRNA vaccine against it is a top priority. Using a lipid nanoparticle-encapsulated mRNA vaccine platform, a panel of multicomponent MPXV vaccine candidates were constructed and prepared, which elicited strong immune responses in mice. Particularly, the penta- and tetra-component vaccine candidates showed superior capability of inducing neutralizing antibodies and protecting mice from VACV challenge. This study provides critical insights for understanding the protection mechanism of MPXV infection and supports further clinical development of these multicomponent mRNA vaccine candidates.

EMERGING MICROBES & INFECTIONS (2023)