scholarly journals Long-Term Iron Deficiency and Dietary Iron Excess Exacerbate Acute Dextran Sodium Sulphate-Induced Colitis and Are Associated with Significant Dysbiosis

2021 ◽  
Vol 22 (7) ◽  
pp. 3646
Author(s):  
Awad Mahalhal ◽  
Michael D. Burkitt ◽  
Carrie A. Duckworth ◽  
Georgina L. Hold ◽  
Barry J. Campbell ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Iron Supplementation ◽  
Sodium Sulphate ◽  
Dietary Iron ◽  
Chronic Colitis ◽  
Dextran Sodium Sulphate ◽  
Acute Colitis ◽  
Long Term Changes ◽  
The Impact

Background: Oral iron supplementation causes gastrointestinal side effects. Short-term alterations in dietary iron exacerbate inflammation and alter the gut microbiota, in murine models of colitis. Patients typically take supplements for months. We investigated the impact of long-term changes in dietary iron on colitis and the microbiome in mice. Methods: We fed mice chow containing differing levels of iron, reflecting deficient (100 ppm), normal (200 ppm), and supplemented (400 ppm) intake for up to 9 weeks, both in absence and presence of dextran sodium sulphate (DSS)-induced chronic colitis. We also induced acute colitis in mice taking these diets for 8 weeks. Impact was assessed (i) clinically and histologically, and (ii) by sequencing the V4 region of 16S rRNA. Results: In mice with long-term changes, the iron-deficient diet was associated with greater weight loss and histological inflammation in the acute colitis model. Chronic colitis was not influenced by altering dietary iron however there was a change in the microbiome in DSS-treated mice consuming 100 ppm and 400 ppm iron diets, and control mice consuming the 400 ppm iron diet. Proteobacteria levels increased significantly, and Bacteroidetes levels decreased, in the 400 ppm iron DSS group at day-63 compared to baseline. Conclusions: Long-term dietary iron alterations affect gut microbiota signatures but do not exacerbate chronic colitis, however acute colitis is exacerbated by such dietary changes. More work is needed to understand the impact of iron supplementation on IBD. The change in the microbiome, in patients with colitis, may arise from the increased luminal iron and not simply from colitis.

scholarly journals Long-term iron deficiency and iron supplementation exacerbate acute DSS-induced colitis and are associated with significant dysbiosis

2019 ◽  
Author(s):  
Awad Mahalhal ◽  
Michael D. Burkitt ◽  
Carrie A. Duckworth ◽  
Georgina L. Hold ◽  
Barry J. Campbell ◽  
...  
Keyword(s):  
Iron Supplementation ◽  
Sodium Sulphate ◽  
Oral Iron ◽  
Dietary Iron ◽  
Chronic Colitis ◽  
Acute Colitis ◽  
Long Term Changes ◽  
Gastrointestinal Side Effects ◽  
The Impact

AbstractPatients taking oral iron supplementation often suffer from gastrointestinal side effects. We have previously shown that acute alterations in oral iron exacerbate dextran sodium sulphate (DSS) induced colitis and are associated with dysbiosis. As patients take iron supplementation for long periods, we asked whether this too would influence colitis and the microbiome. We assessed the impact of long-term changes in dietary iron, by feeding chow containing 100ppm, 200ppm and 400ppm (reflecting a deficient, normal or supplemented diet, respectively) for up to 9 weeks to female wild-type C57BL/6 (WT) mice in presence or absence of chronic colitis, or acute colitis induced after 8 weeks, induced by DSS. Assessment was made based on (i) clinical and histological severity of colitis, and (ii) faecal microbial diversity, as assessed by sequencing the V4 region of16SrRNA. In mice with long term changes to their dietary iron, reduced iron intake (100ppm iron diet) was associated with increased weight loss and histology scoring in the acute colitis model. Chronic colitis was not influenced by altering dietary iron however there was a clear change in the faecal microbiome in the 100 and 400ppm iron DSS-treated groups and in controls consuming the 400ppm iron diet. Proteobacteria levels increased significantly at day-63 compared to baseline and Bacteroidetes levels decreased in the 400ppm iron DSS group at day-63 compared to baseline; mirroring our previously published work in acute colitis. Long term dietary iron alterations clearly affects gut microbiota signatures but do not appear to exacerbate chronic colitis. However, acute colitis is exacerbated by changes in dietary iron. More work is needed to understand the impact of iron supplementation of the pathologenesis of IBD and rise that possiblity that the change in the microbiome, in patients with colitis, is a consequence of the increase in luminal iron and not simply the presence of colitis.

scholarly journals Postoperative Complications Are Associated with Long-Term Changes in the Gut Microbiota Following Colorectal Cancer Surgery

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 246
Author(s):  
Felix C.F. Schmitt ◽  
Martin Schneider ◽  
William Mathejczyk ◽  
Markus A. Weigand ◽  
Jane C. Figueiredo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Postoperative Complications ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Tumor Resection ◽  
Microbial Composition ◽  
Colorectal Cancer Surgery ◽  
Long Term Changes ◽  
Stool Samples

Changes in the gut microbiome have already been associated with postoperative complications in major abdominal surgery. However, it is still unclear whether these changes are transient or a long-lasting effect. Therefore, the aim of this prospective clinical pilot study was to examine long-term changes in the gut microbiota and to correlate these changes with the clinical course of the patient. Methods: In total, stool samples of 62 newly diagnosed colorectal cancer patients undergoing primary tumor resection were analyzed by 16S-rDNA next-generation sequencing. Stool samples were collected preoperatively in order to determine the gut microbiome at baseline as well as at 6, 12, and 24 months thereafter to observe longitudinal changes. Postoperatively, the study patients were separated into two groups—patients who suffered from postoperative complications (n = 30) and those without complication (n = 32). Patients with postoperative complications showed a significantly stronger reduction in the alpha diversity starting 6 months after operation, which does not resolve, even after 24 months. The structure of the microbiome was also significantly altered from baseline at six-month follow-up in patients with complications (p = 0.006). This was associated with a long-lasting decrease of a large number of species in the gut microbiota indicating an impact in the commensal microbiota and a long-lasting increase of Fusobacterium ulcerans. The microbial composition of the gut microbiome shows significant changes in patients with postoperative complications up to 24 months after surgery.

scholarly journals Titanium Dioxide Presents a Different Profile in Dextran Sodium Sulphate-Induced Experimental Colitis in Mice Lacking the IBD Risk Gene Ptpn2 in Myeloid Cells

2021 ◽  
Vol 22 (2) ◽  
pp. 772
Author(s):  
Javier Conde ◽  
Marlene Schwarzfischer ◽  
Egle Katkeviciute ◽  
Janine Häfliger ◽  
Anna Niechcial ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Titanium Dioxide ◽  
Genetic Risk ◽  
Intestinal Inflammation ◽  
Sodium Sulphate ◽  
Food Additive ◽  
Wild Type ◽  
Dextran Sodium Sulphate ◽  
Risk Gene ◽  
The Impact

Environmental and genetic factors have been demonstrated to contribute to the development of inflammatory bowel disease (IBD). Recent studies suggested that the food additive; titanium dioxide (TiO2) might play a causative role in the disease. Therefore, in the present study we aimed to explore the interaction between the food additive TiO2 and the well-characterized IBD risk gene protein tyrosine phosphatase non-receptor type 2 (Ptpn2) and their role in the development of intestinal inflammation. Dextran sodium sulphate (DSS)-induced acute colitis was performed in mice lacking the expression of Ptpn2 in myeloid cells (Ptpn2LysMCre) or their wild type littermates (Ptpn2fl/fl) and exposed to the microparticle TiO2. The impact of Ptpn2 on TiO2 signalling pathways and TiO2-induced IL-1β and IL-10 levels were studied using bone marrow-derived macrophages (BMDMs). Ptpn2LysMCre exposed to TiO2 exhibited more severe intestinal inflammation than their wild type counterparts. This effect was likely due to the impact of TiO2 on the differentiation of intestinal macrophages, suppressing the number of anti-inflammatory macrophages in Ptpn2 deficient mice. Moreover, we also found that TiO2 was able to induce the secretion of IL-1β via mitogen-activated proteins kinases (MAPKs) and to repress the expression of IL-10 in bone marrow-derived macrophages via MAPK-independent pathways. This is the first evidence of the cooperation between the genetic risk factor Ptpn2 and the environmental factor TiO2 in the regulation of intestinal inflammation. The results presented here suggest that the ingestion of certain industrial compounds should be taken into account, especially in individuals with increased genetic risk

scholarly journals Dietary Interventions to Prevent High Fructose Diet-associated Worsening of Colitis and Colitis-associated Tumorigenesis in Mice

2021 ◽  
Author(s):  
Ryohei Nishiguchi ◽  
Srijani Basu ◽  
Hannah A Staab ◽  
Naotake Ito ◽  
Xi Kathy Zhou ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Diet ◽  
Experimental Colitis ◽  
Protective Effects ◽  
Diet Change ◽  
Chronic Colitis ◽  
Acute Colitis ◽  
High Fructose Diet ◽  
High Consumption ◽  
High Fructose

Abstract Diet is believed to be an important factor in the pathogenesis of Inflammatory Bowel Disease. High consumption of dietary fructose has been shown to exacerbate experimental colitis, an effect mediated through the gut microbiota. This study evaluated whether dietary alterations could attenuate the detrimental effects of a high fructose diet (HFrD) in experimental colitis. First, we determined whether the pro-colitic effects of a HFrD could be reversed by switching mice from a HFrD to a control diet. This diet change completely prevented HFrD-induced worsening of acute colitis, in association with a rapid normalization of the microbiota. Second, we tested the effects of dietary fiber, which demonstrated that psyllium was the most effective type of fiber for protecting against HFrD-induced worsening of acute colitis, compared to pectin, inulin or cellulose. In fact, supplemental psyllium nearly completely prevented the detrimental effects of the HFrD, an effect associated with a shift in the gut microbiota. We next determined whether the protective effects of these interventions could be extended to chronic colitis and colitis-associated tumorigenesis. Using the azoxymethane/dextran sodium sulfate model, we first demonstrated that HFrD feeding exacerbated chronic colitis and increased colitis-associated tumorigenesis. Using the same dietary changes tested in the acute colitis setting, we also showed that mice were protected from HFrD-mediated enhanced chronic colitis and tumorigenesis, upon either diet switching or psyllium supplementation. Taken together, these findings suggest that high consumption of fructose may enhance colon tumorigenesis associated with long-standing colitis, an effect that could be reduced by dietary alterations.

scholarly journals Antibiotics at birth and later antibiotic courses: effects on gut microbiota

2021 ◽  
Author(s):  
Sofia Ainonen ◽  
Mysore V Tejesvi ◽  
Md. Rayhan Mahmud ◽  
Niko Paalanne ◽  
Tytti Pokka ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Group ◽  
List Type ◽  
Antibiotic Exposure ◽  
Microbiota Composition ◽  
Long Term Effects ◽  
The Impact ◽  
Antibiotic Courses ◽  
Gut Microbiota Composition

Abstract Background Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. Methods This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. Results Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). Conclusions Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. Impact Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

scholarly journals Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota

2021 ◽  
Vol 12 (2) ◽  
pp. 491-502
Author(s):  
Sarah R. Bloor ◽  
Rudolph Schutte ◽  
Anthony R. Hobson
Keyword(s):  
Side Effects ◽  
Gut Microbiota ◽  
Iron Supplementation ◽  
Methanogenic Archaea ◽  
Intravenous Iron ◽  
Oral Iron ◽  
Intestinal Lumen ◽  
Gastrointestinal Side Effects ◽  
Potential Link ◽  
The Impact

Iron deficiency anaemia (IDA) is a worldwide healthcare problem affecting approximately 25% of the global population. The most common IDA treatment is oral iron supplementation, which has been associated with gastrointestinal (GI) side effects such as constipation and bloating. These can result in treatment non-adherence and the persistence of IDA. Intravenous iron does not cause GI side effects, which may be due to the lack of exposure to the intestinal lumen. Luminal iron can cause changes to the gut microbiota, aiding the promotion of pathogenic species and decreasing beneficial protective species. Iron is vital for methanogenic archaea, which rely on iron for growth and metabolism. Increased intestinal methane has been associated with slowing of intestinal transit, constipation, and bloating. Here we explore the literature to understand a potential link between iron and methanogenesis as a novel way to understand the mechanism of oral iron supplementation induced GI side effects.

scholarly journals Depletion of acetate-producing bacteria from the gut microbiota facilitates cognitive impairment through the gut-brain neural mechanism in diabetic mice

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Hong Zheng ◽  
Pengtao Xu ◽  
Qiaoying Jiang ◽  
Qingqing Xu ◽  
Yafei Zheng ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Cognitive Functions ◽  
Neural Mechanism ◽  
Fecal Microbiota ◽  
Protective Role ◽  
Fecal Microbiota Transplant ◽  
Memory Impairments ◽  
The Impact

Abstract Background Modification of the gut microbiota has been reported to reduce the incidence of type 1 diabetes mellitus (T1D). We hypothesized that the gut microbiota shifts might also have an effect on cognitive functions in T1D. Herein we used a non-absorbable antibiotic vancomycin to modify the gut microbiota in streptozotocin (STZ)-induced T1D mice and studied the impact of microbial changes on cognitive performances in T1D mice and its potential gut-brain neural mechanism. Results We found that vancomycin exposure disrupted the gut microbiome, altered host metabolic phenotypes, and facilitated cognitive impairment in T1D mice. Long-term acetate deficiency due to depletion of acetate-producing bacteria resulted in the reduction of synaptophysin (SYP) in the hippocampus as well as learning and memory impairments. Exogenous acetate supplement or fecal microbiota transplant recovered hippocampal SYP level in vancomycin-treated T1D mice, and this effect was attenuated by vagal inhibition or vagotomy. Conclusions Our results demonstrate the protective role of microbiota metabolite acetate in cognitive functions and suggest long-term acetate deficiency as a risk factor of cognitive decline.

scholarly journals The Impact of Low-Level Iron Supplements on the Faecal Microbiota of Irritable Bowel Syndrome and Healthy Donors Using In Vitro Batch Cultures

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3819
Author(s):  
Carlos Poveda ◽  
Dora I. A. Pereira ◽  
Marie C. Lewis ◽  
Gemma E. Walton
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiota ◽  
Iron Supplementation ◽  
Ferrous Sulphate ◽  
Fluorescence In Situ Hybridisation ◽  
Batch Cultures ◽  
Low Level ◽  
Irritable Bowel ◽  
The Impact

Ferrous iron supplementation has been reported to adversely alter the gut microbiota in infants. To date, the impact of iron on the adult microbiota is limited, particularly at low supplementary concentrations. The aim of this research was to explore the impact of low-level iron supplementation on the gut microbiota of healthy and Irritable Bowel Syndrome (IBS) volunteers. Anaerobic, pH-controlled in vitro batch cultures were inoculated with faeces from healthy or IBS donors along with iron (ferrous sulphate, nanoparticulate iron and pea ferritin (50 μmol−1 iron)). The microbiota were explored by fluorescence in situ hybridisation coupled with flow cytometry. Furthermore, metabolite production was assessed by gas chromatography. IBS volunteers had different starting microbial profiles to healthy controls. The sources of iron did not negatively impact the microbial population, with results of pea ferritin supplementation being similar to nanoparticulate iron, whilst ferrous sulphate led to enhanced Bacteroides spp. The metabolite data suggested no shift to potentially negative proteolysis. The results indicate that low doses of iron from the three sources were not detrimental to the gut microbiota. This is the first time that pea ferritin fermentation has been tested and indicates that low dose supplementation of iron is unlikely to be detrimental to the gut microbiota.

Long‐term changes in the gut microbiota after 14‐day bismuth quadruple therapy in penicillin‐allergic children

Helicobacter ◽  
2020 ◽  
Vol 25 (5) ◽  
Author(s):  
Ying Zhou ◽  
Ziqing Ye ◽  
Junping Lu ◽  
Shijian Miao ◽  
Xiaolan Lu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Quadruple Therapy ◽  
Long Term Changes

scholarly journals Impact of a Model Used to Simulate Chronic Socio-Environmental Stressors Encountered during Spaceflight on Murine Intestinal Microbiota

2020 ◽  
Vol 21 (21) ◽  
pp. 7863
Author(s):  
Corentine Alauzet ◽  
Lisiane Cunat ◽  
Maxime Wack ◽  
Laurence Lanfumey ◽  
Christine Legrand-Frossi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Space Mission ◽  
Psychosocial Stressors ◽  
Mild Stress ◽  
Protective Properties ◽  
Β Diversity ◽  
Intestinal Dysbiosis ◽  
The Impact

During deep-space travels, crewmembers face various physical and psychosocial stressors that could alter gut microbiota composition. Since it is well known that intestinal dysbiosis is involved in the onset or exacerbation of several disorders, the aim of this study was to evaluate changes in intestinal microbiota in a murine model used to mimic chronic psychosocial stressors encountered during a long-term space mission. We demonstrate that 3 weeks of exposure to this model (called CUMS for Chronic Unpredictable Mild Stress) induce significant change in intracaecal β-diversity characterized by an important increase of the Firmicutes/Bacteroidetes ratio. These alterations are associated with a decrease of Porphyromonadaceae, particularly of the genus Barnesiella, a major member of gut microbiota in mice and humans where it is described as having protective properties. These results raise the question of the impact of stress-induced decrease of beneficial taxa, support recent data deduced from in-flight experimentations and other ground-based models, and emphasize the critical need for further studies exploring the impact of spaceflight on intestinal microbiota in order to propose strategies to countermeasure spaceflight-associated dysbiosis and its consequences on health.

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