The Impact of the Intestinal Microbiota in Therapeutic Responses Against Cancer

Studying potential dietary exposure to antimicrobial drug residues via meat and dairy products is essential to ensure human health and consumer safety. When studying how antimicrobial residues in food impact the development of antimicrobial drug resistance and disrupt normal bacteria community structure in the intestine, there are diverse methodological challenges to overcome. In this study, traditional cultures and molecular analysis techniques were used to determine the effects of tetracycline at chronic subinhibitory exposure levels on human intestinal microbiota using an in vitro continuous flow bioreactor. Six bioreactor culture vessels containing human fecal suspensions were maintained at 37 °C for 7 days. After a steady state was achieved, the suspensions were dosed with 0, 0.015, 0.15, 1.5, 15, or 150 µg/mL tetracycline, respectively. Exposure to 150 µg/mL tetracycline resulted in a decrease of total anaerobic bacteria from 1.9 × 107 ± 0.3 × 107 down to 2 × 106 ± 0.8 × 106 CFU/mL. Dose-dependent effects of tetracycline were noted for perturbations of tetB and tetD gene expression and changes in acetate and propionate concentrations. Although no-observed-adverse-effect concentrations differed, depending on the traditional cultures and the molecular analysis techniques used, this in vitro continuous flow bioreactor study contributes to the knowledge base regarding the impact of chronic exposure of tetracycline on human intestinal microbiota.

Download Full-text

Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage

Cell Communication and Signaling ◽

10.1186/s12964-021-00712-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Camille Ternet ◽

Christina Kiel

Keyword(s):

Colorectal Cancer ◽

Signaling Pathways ◽

Intestinal Microbiota ◽

Critical Role ◽

Neuroendocrine Cells ◽

Cell Junction ◽

Intestinal Cell ◽

Intestinal Homeostasis ◽

Cell Functions ◽

The Impact

AbstractThe intestinal epithelium acts as a physical barrier that separates the intestinal microbiota from the host and is critical for preserving intestinal homeostasis. The barrier is formed by tightly linked intestinal epithelial cells (IECs) (i.e. enterocytes, goblet cells, neuroendocrine cells, tuft cells, Paneth cells, and M cells), which constantly self-renew and shed. IECs also communicate with microbiota, coordinate innate and adaptive effector cell functions. In this review, we summarize the signaling pathways contributing to intestinal cell fates and homeostasis functions. We focus especially on intestinal stem cell proliferation, cell junction formation, remodelling, hypoxia, the impact of intestinal microbiota, the immune system, inflammation, and metabolism. Recognizing the critical role of KRAS mutants in colorectal cancer, we highlight the connections of KRAS signaling pathways in coordinating these functions. Furthermore, we review the impact of KRAS colorectal cancer mutants on pathway rewiring associated with disruption and dysfunction of the normal intestinal homeostasis. Given that KRAS is still considered undruggable and the development of treatments that directly target KRAS are unlikely, we discuss the suitability of targeting pathways downstream of KRAS as well as alterations of cell extrinsic/microenvironmental factors as possible targets for modulating signaling pathways in colorectal cancer.

Download Full-text

The impact of Opisthorchis felineus infection and praziquantel treatment on the intestinal microbiota in children

Acta Tropica ◽

10.1016/j.actatropica.2021.105835 ◽

2021 ◽

Vol 217 ◽

pp. 105835

Author(s):

Tatiana S. Sokolova ◽

Vyacheslav A. Petrov ◽

Irina V. Saltykova ◽

Yulia B. Dorofeeva ◽

Alexander V. Tyakht ◽

...

Keyword(s):

Intestinal Microbiota ◽

Opisthorchis Felineus ◽

Praziquantel Treatment ◽

The Impact

Download Full-text

Intestinal microbiota and its effect on the immune system — A nested case-cohort study on prevention of atopy among small children in Trondheim: The IMPACT study

Contemporary Clinical Trials ◽

10.1016/j.cct.2006.02.009 ◽

2006 ◽

Vol 27 (4) ◽

pp. 389-395 ◽

Cited By ~ 18

Author(s):

Torbjørn Øien ◽

Ola Storrø ◽

Roar Johnsen

Keyword(s):

Cohort Study ◽

Immune System ◽

Intestinal Microbiota ◽

Impact Study ◽

Small Children ◽

System A ◽

The Impact

Download Full-text

Intestinal Microbiota and Allergy. Probiotics and Prebiotics in Prevention and Treatment of Allergic Diseases

Педиатрическая фармакология ◽

10.15690/pf.v16i1.1999 ◽

2019 ◽

Vol 16 (1) ◽

pp. 7-18 ◽

Cited By ~ 3

Author(s):

Svetlana G. Makarova ◽

Leyla S. Namazova-Baranova ◽

Oksana A. Ereshko ◽

Dmitry S. Yasakov ◽

Pavel E. Sadchikov

Keyword(s):

Immune Response ◽

Clinical Trials ◽

Intestinal Microbiota ◽

Practical Interest ◽

Allergic Diseases ◽

Evidence Based ◽

Prevention And Treatment ◽

The Impact ◽

Positive Results ◽

Intestinal Microbiocenosis

Intestinal microbiota is the factor that identifies considerably the human health. The impact of the microbial factor on a child begins long before his birth. Children have certain features in forming of immune response and intestinal microbiocenosis even before birth. Decline in diversity of intestinal microbiota is common in children with allergic disease even during first months of life, before allergic pathology development. Capabilities for microbiota development adjustment are sufficiently restricted. However it is clinically proven that early (within the first hours of life) breastfeeding attachment, breastfeeding itself within at least first 6 months of life, the use of prebiotics in milk formulas as well as the use of probiotics can give positive results on allergy management. In this review we present results of recent metaanalyses and consensus papers of international medical communities about use of probiotics and prebiotics in prevention and treatment of allergic diseases. Despite great scientific and practical interest to this topic, authors of metaanalyses bring our attention to the lack of evidence-based clinical trials.

Download Full-text

Heat Stress Alters the Intestinal Microbiota and Metabolomic Profiles in Mice

Frontiers in Microbiology ◽

10.3389/fmicb.2021.706772 ◽

2021 ◽

Vol 12 ◽

Cited By ~ 1

Author(s):

Chaoyue Wen ◽

Siyu Li ◽

Jiaojiao Wang ◽

Yimin Zhu ◽

Xin Zong ◽

...

Keyword(s):

Heat Stress ◽

Fatty Acid ◽

High Temperature ◽

Intestinal Microbiota ◽

High Throughput Sequencing ◽

Acid Metabolism ◽

Core Body Temperature ◽

Control Group ◽

Serum Biochemical ◽

The Impact

BackgroundHeat stress has negative effects on the intestinal health of humans and animals. However, the impact of heat stress on intestinal microbial and metabolic changes remains elusive. Here, we investigated the cecal microbial and metabolic profiles in mice in response to heat stress.MethodsThe mouse heat stress model was constructed by simulating a high-temperature environment. Twenty mice were randomly assigned to two groups, the control group (CON, 25°C) and the heat treatment group (HS, 40°C from 13:00 to 15:00 every day for 7 days). Serum and cecal contents were collected from the mice for serum biochemical analysis, 16S rRNA high-throughput sequencing, and non-targeted metabolomics.ResultsBoth core body temperature and water intake were significantly increased in the HS group. Serum biochemical indicators were also affected, including significantly increased triglyceride and decreased low-density lipoprotein in the heat stress group. The composition and structure of intestinal microbiota were remarkably altered in the HS group. At the species level, the relative abundance of Candidatus Arthromitus sp. SFB-mouse-Japan and Lactobacillus murinus significantly reduced, while that of Lachnospiraceae bacterium 3-1 obviously increased after HS. Metabolomic analysis of the cecal contents clearly distinguished metabolite changes between the groups. The significantly different metabolites identified were mainly involved in the fatty acid synthesis, purine metabolism, fatty acid metabolism, cyanoamino acid metabolism, glyceride metabolism, and plasmalogen synthesis.ConclusionIn summary, high temperature disrupted the homeostatic balance of the intestinal microbiota in mice and also induced significant alterations in intestinal metabolites. This study provides a basis for treating intestinal disorders caused by elevated temperature in humans and animals and can further formulate nutritional countermeasures to reduce heat stress-induced damage.

Download Full-text

Exposure to Arsenite in CD-1 Mice during Juvenile and Adult Stages: Effects on Intestinal Microbiota and Gut-Associated Immune Status

mBio ◽

10.1128/mbio.01418-18 ◽

2018 ◽

Vol 9 (4) ◽

Cited By ~ 16

Author(s):

Kuppan Gokulan ◽

Matthew G. Arnold ◽

Jake Jensen ◽

Michelle Vanlandingham ◽

Nathan C. Twaddle ◽

...

Keyword(s):

Intestinal Microbiota ◽

Immune Status ◽

Arsenic Exposure ◽

Intestinal Bacteria ◽

Repeated Exposure ◽

Potential Toxicity ◽

Microbial Composition ◽

Arsenic Resistance ◽

Immune System Development ◽

The Impact

ABSTRACT Intestinal microbiota composition and gut-associated immune response can contribute to the toxicity of arsenic. We investigated the potential toxicity of short-term arsenic exposure on gut microbiome composition, intestinal immune status, microbial arsenic resistance gene, and arsenic metabolic profiles in adult and developmental stages of CD-1 mice. The potential toxicity of arsenite [As(III)] was determined for two life stages: (i) adult animals at 24 or 48 h after single gavage (0.05 mg/kg body weight [b.w.] [low dose], 0.1 mg/kg b.w. [medium dose], and 0.2 mg/kg b.w. [high dose]) and repeated exposure at 1 mg/liter for 8 days and (ii) postnatal day 10 (PND10) and PND21 after single gavage (0.05 mg/kg b.w.). Dose- and time-dependent responses in bacterial recovery/microbial composition were observed in adults after a single gavage. Repeated exposure caused a transient decrease in the recovery of intestinal bacteria, a shift in the bacterial population with abundance of arsenic resistance genes, and evidence for host metabolism of arsenite into less-reactive trivalent methylated species. Arsenic exposure in adult animals induced high levels of CC chemokines and of proinflammatory and anti-inflammatory cytokine secretion in intestine. Arsenic exposure at PND21 resulted in the development of distinct bacterial populations. Results of this study highlight significant changes in the intestinal microbiome and gut-associated immune status during a single or repeated exposure to arsenic in juvenile and adult animals. The data warrant investigation of the long-term effects of oral arsenic exposure on the microbiome and of immune system development and responses. IMPORTANCE Transformation of organic arsenic to toxic inorganic arsenic (iAs) is likely carried out by intestinal bacteria, and iAs may alter the viability of certain microbial populations. This study addressed the impact of arsenic exposure on intestinal microbiota diversity and host gut-associated immune mediators during early development or adulthood using scenarios of acute or repeated doses. During acute arsenic exposure, animals developed defense functions characterized by higher abundances of bacteria that are involved in arsenic resistance or detoxification mechanisms. Arsenite had a negative effect on the abundance of bacterial species that are involved in the conversion of protein to butyrate, which is an alternative energy source in the intestine. The intestinal mucosal immune cytokine profile reflected a mechanism of protection from arsenic toxicity.

Download Full-text

Influence of the Intestinal Microbiota on Colonization Resistance to Salmonella and the Shedding Pattern of Naturally Exposed Pigs

mSystems ◽

10.1128/msystems.00021-19 ◽

2019 ◽

Vol 4 (2) ◽

Cited By ~ 9

Author(s):

Héctor Argüello ◽

Jordi Estellé ◽

Finola C. Leonard ◽

Fiona Crispie ◽

Paul D. Cotter ◽

...

Keyword(s):

Public Health ◽

16S Rrna ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Current Control ◽

Growing Pigs ◽

Microbiota Composition ◽

Core Microbiome ◽

The Core ◽

The Impact

ABSTRACT Salmonella colonization and infection in production animals such as pigs are a cause for concern from a public health perspective. Variations in susceptibility to natural infection may be influenced by the intestinal microbiota. Using 16S rRNA compositional sequencing, we characterized the fecal microbiome of 15 weaned pigs naturally infected with Salmonella at 18, 33, and 45 days postweaning. Dissimilarities in microbiota composition were analyzed in relation to Salmonella infection status (infected, not infected), serological status, and shedding pattern (nonshedders, single-point shedders, intermittent-persistent shedders). Global microbiota composition was associated with the infection outcome based on serological analysis. Greater richness within the microbiota postweaning was linked to pigs being seronegative at the end of the study at 11 weeks of age. Members of the Clostridia, such as Blautia, Roseburia, and Anaerovibrio, were more abundant and part of the core microbiome in nonshedder pigs. Cellulolytic microbiota (Ruminococcus and Prevotella) were also more abundant in noninfected pigs during the weaning and growing stages. Microbial profiling also revealed that infected pigs had a higher abundance of Lactobacillus and Oscillospira, the latter also being part of the core microbiome of intermittent-persistent shedders. These findings suggest that a lack of microbiome maturation and greater proportions of microorganisms associated with suckling increase susceptibility to infection. In addition, the persistence of Salmonella shedding may be associated with an enrichment of pathobionts such as Anaerobiospirillum. Overall, these results suggest that there may be merit in manipulating certain taxa within the porcine intestinal microbial community to increase disease resistance against Salmonella in pigs. IMPORTANCE Salmonella is a global threat for public health, and pork is one of the main sources of human salmonellosis. However, the complex epidemiology of the infection limits current control strategies aimed at reducing the prevalence of this infection in pigs. The present study analyzes for the first time the impact of the gut microbiota in Salmonella infection in pigs and its shedding pattern in naturally infected growing pigs. Microbiome (16S rRNA amplicon) analysis reveals that maturation of the gut microbiome could be a key consideration with respect to limiting the infection and shedding of Salmonella in pigs. Indeed, seronegative animals had higher richness of the gut microbiota early after weaning, and uninfected pigs had higher abundance of strict anaerobes from the class Clostridia, results which demonstrate that a fast transition from the suckling microbiota to a postweaning microbiota could be crucial with respect to protecting the animals.

Download Full-text

Considerations for the design and conduct of human gut microbiota intervention studies relating to foods

European Journal of Nutrition ◽

10.1007/s00394-020-02232-1 ◽

2020 ◽

Vol 59 (8) ◽

pp. 3347-3368

Author(s):

J. R. Swann ◽

M. Rajilic-Stojanovic ◽

A. Salonen ◽

O. Sakwinska ◽

C. Gill ◽

...

Keyword(s):

Gut Microbiota ◽

Intestinal Microbiota ◽

Intervention Studies ◽

Health Claims ◽

Host Responses ◽

Human Gut ◽

Eligibility Criteria ◽

Functional Changes ◽

Human Gut Microbiota ◽

The Impact

AbstractWith the growing appreciation for the influence of the intestinal microbiota on human health, there is increasing motivation to design and refine interventions to promote favorable shifts in the microbiota and their interactions with the host. Technological advances have improved our understanding and ability to measure this indigenous population and the impact of such interventions. However, the rapid growth and evolution of the field, as well as the diversity of methods used, parameters measured and populations studied, make it difficult to interpret the significance of the findings and translate their outcomes to the wider population. This can prevent comparisons across studies and hinder the drawing of appropriate conclusions. This review outlines considerations to facilitate the design, implementation and interpretation of human gut microbiota intervention studies relating to foods based upon our current understanding of the intestinal microbiota, its functionality and interactions with the human host. This includes parameters associated with study design, eligibility criteria, statistical considerations, characterization of products and the measurement of compliance. Methodologies and markers to assess compositional and functional changes in the microbiota, following interventions are discussed in addition to approaches to assess changes in microbiota–host interactions and host responses. Last, EU legislative aspects in relation to foods and health claims are presented. While it is appreciated that the field of gastrointestinal microbiology is rapidly evolving, such guidance will assist in the design and interpretation of human gut microbiota interventional studies relating to foods.

Download Full-text