Oral iron supplementation after antibiotic exposure induces a deleterious recovery of the gut microbiota

Abstract Background Oral iron supplementation is commonly prescribed for anemia and may play an important role in the gut microbiota recovery of anemic individuals who received antibiotic treatment. This study aims to investigate the effects of iron supplementation on gut microbiota recovery after antibiotics exposure. Results Mice were subjected to oral antibiotic treatment with neomycin and metronidazole and were fed diets with different concentrations of iron. The composition of the gut microbiota was followed throughout treatment by 16S rRNA sequencing of DNA extracted from fecal samples. Gut microbiota functions were inferred using PICRUSt2, and short-chain fatty acid concentration in fecal samples was assessed by liquid-chromatography mass spectrometry. Iron supplementation after antibiotic exposure shifted the gut microbiota composition towards a Bacteroidetes phylum-dominant composition. At the genus level, the iron-supplemented diet induced an increase in the abundance of Parasutterella and Bacteroides, and a decrease of Bilophila and Akkermansia. Parasutterella excrementihominis, Bacteroides vulgatus, and Alistipes finegoldii, were more abundant with the iron excess diet. Iron-induced shifts in microbiota composition were accompanied by functional modifications, including an enhancement of the biosynthesis of primary bile acids, nitrogen metabolism, cyanoamino acid metabolism and pentose phosphate pathways. Recovery after antibiotic treatment increased propionate levels independent of luminal iron levels, whereas butyrate levels were diminished by excess iron. Conclusions Oral iron supplementation after antibiotic therapy in mice may lead to deleterious changes in the recovery of the gut microbiota. Our results have implications on the use of oral iron supplementation after antibiotic exposure and justify further studies on alternative treatments for anemia in these settings.

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A34 ANTIBIOTIC TREATMENT AND ORAL IRON SUPPLEMENTATION SHAPE THE COMPOSITION, RECOVERY AND FUNCTION OF THE GUT MICROBIOTA

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.033 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 134-135

Author(s):

T Cuisiniere ◽

M Oliero ◽

R Hajjar ◽

A Calve ◽

G Fragoso ◽

...

Keyword(s):

Gut Microbiota ◽

Antibiotic Treatment ◽

Iron Supplementation ◽

Bacterial Species ◽

Recovery Period ◽

Iron Concentration ◽

Pentose Phosphate ◽

Oral Iron ◽

Antibiotic Exposure ◽

Recherche Médicale

Abstract Background Colorectal cancer (CRC) induces anemia in a large proportion of patients and is usually treated with oral iron supplementation. Surgery, the main treatment for CRC, is routinely accompanied by prophylactic antibiotics to avoid infection. However, the combined effect of antibiotics and luminal iron in the gut on the microbiota and intestinal homeostasis remains unknown. Aims We aim to characterize the dynamics of gut microbiota composition and recovery from antibiotic exposure under iron-sufficient and iron-supplemented diets in mice. We will investigate how microbial shifts induced by antibiotics and iron influence the function of the gut microbiota and metabolites in the gut. Methods Mice were subjected to antibiotic treatment with different concentrations of dietary iron. The composition of the gut microbiota and its recovery after these interventions were assessed in stool samples by 16S rRNA sequencing before and after antibiotic exposure and during the recovery period. Gut microbiota functions were inferred by using the PICRUSt2 prediction tool, and short chain fatty acid (SCFA) concentration in feces were assessed by liquid-chromatography mass spectrometry. Results Recovery from antibiotics under high luminal iron concentration shifted the gut microbiota toward a Bacteroidetes phylum-dominant composition. Four bacterial species characterized as CRC markers and/or CRC initiators were significantly more abundant, and nitrogen and pentose phosphate metabolism were higher after recovery under oral iron supplementation. Antibiotic exposure induced a long-term increase in SCFAs linked to gut inflammation, propionate and succinate, and was independent of luminal iron concentration. For mice recovering from antibiotics under high luminal iron concentration, they showed a lack of recovery in baseline levels of butyrate, a SCFA that inhibits cancer cell proliferation in the gut. Conclusions Gut microbiota recovery from antibiotic exposure under oral iron supplementation is frequent in CRC patients, but is also common in the general population. This study identifies possible deleterious effects of the concomitance of these two disruptive agents of the gut microbiota and may lead to modifications in the management of anemia in patients with CRC. Funding Agencies CIHR Bourse de Mérite Rougier-Armandie en recherche médicale de la Faculté de médecine

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

Pediatric Research ◽

10.1038/s41390-021-01494-7 ◽

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.

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

Microbiology Research ◽

10.3390/microbiolres12020033 ◽

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.

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Emergence of nosocomial associated opportunistic pathogens in the gut microbiome after antibiotic treatment

Antimicrobial Resistance and Infection Control ◽

10.1186/s13756-021-00903-0 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Isaac Raplee ◽

Lacey Walker ◽

Lei Xu ◽

Anil Surathu ◽

Ashok Chockalingam ◽

...

Keyword(s):

Gut Microbiota ◽

Antibiotic Therapy ◽

Antibiotic Treatment ◽

Nosocomial Infections ◽

Pathogenic Bacteria ◽

Antibiotic Administration ◽

Oral Antibiotic ◽

Opportunistic Pathogens ◽

Taxonomic Assignment ◽

Antibiotic Resistant

Abstract Introduction According to the Centers for Disease Control’s 2015 Hospital Acquired Infection Hospital Prevalence Survey, 1 in 31 hospital patients was infected with at least one nosocomial pathogen while being treated for unrelated issues. Many studies associate antibiotic administration with nosocomial infection occurrence. However, to our knowledge, there is little to no direct evidence of antibiotic administration selecting for nosocomial opportunistic pathogens. Aim This study aims to confirm gut microbiota shifts in an animal model of antibiotic treatment to determine whether antibiotic use favors pathogenic bacteria. Methodology We utilized next-generation sequencing and in-house metagenomic assembly and taxonomic assignment pipelines on the fecal microbiota of a urinary tract infection mouse model with and without antibiotic treatment. Results Antibiotic therapy decreased the number of detectable species of bacteria by at least 20-fold. Furthermore, the gut microbiota of antibiotic treated mice had a significant increase of opportunistic pathogens that have been implicated in nosocomial infections, like Acinetobacter calcoaceticus/baumannii complex, Chlamydia abortus, Bacteroides fragilis, and Bacteroides thetaiotaomicron. Moreover, antibiotic treatment selected for antibiotic resistant gene enriched subpopulations for many of these opportunistic pathogens. Conclusions Oral antibiotic therapy may select for common opportunistic pathogens responsible for nosocomial infections. In this study opportunistic pathogens present after antibiotic therapy harbored more antibiotic resistant genes than populations of opportunistic pathogens before treatment. Our results demonstrate the effects of antibiotic therapy on induced dysbiosis and expansion of opportunistic pathogen populations and antibiotic resistant subpopulations of those pathogens. Follow-up studies with larger samples sizes and potentially controlled clinical investigations should be performed to confirm our findings.

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Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period

Translational Psychiatry ◽

10.1038/s41398-020-01073-0 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Gilliard Lach ◽

Christine Fülling ◽

Thomaz F. S. Bastiaanssen ◽

Fiona Fouhy ◽

Aoife N. O’ Donovan ◽

...

Keyword(s):

Gene Expression ◽

Gut Microbiota ◽

Antibiotic Treatment ◽

Brain Function ◽

Early Life ◽

Microbiota Composition ◽

Microbial Composition ◽

Extrinsic Factors ◽

Neurobehavioral Effects ◽

Adolescent Period

Abstract The gut microbiota is an essential regulator of many aspects of host physiology. Disruption of gut microbial communities affects gut-brain communication which ultimately can manifest as changes in brain function and behaviour. Transient changes in gut microbial composition can be induced by various intrinsic and extrinsic factors, however, it is possible that enduring shifts in the microbiota composition can be achieved by perturbation at a timepoint when the gut microbiota has not fully matured or is generally unstable, such as during early life or ageing. In this study, we investigated the effects of 3-week microbiota depletion with antibiotic treatment during the adolescent period and in adulthood. Following a washout period to restore the gut microbiota, behavioural and molecular hallmarks of gut-brain communication were investigated. Our data revealed that transient microbiota depletion had long-lasting effects on microbiota composition and increased anxiety-like behaviour in mice exposed to antibiotic treatment during adolescence but not in adulthood. Similarly, gene expression in the amygdala was more severely affected in mice treated during adolescence. Taken together these data highlight the vulnerability of the gut microbiota during the critical adolescent period and the long-lasting impact manipulations of the microbiota can have on gene expression and behaviour in adulthood.

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Deep Transcranial Magnetic Stimulation Affects Gut Microbiota Composition in Obesity: Results of Randomized Clinical Trial

International Journal of Molecular Sciences ◽

10.3390/ijms22094692 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4692

Author(s):

Anna Ferrulli ◽

Lorenzo Drago ◽

Sara Gandini ◽

Stefano Massarini ◽

Federica Bellerba ◽

...

Keyword(s):

Transcranial Magnetic Stimulation ◽

Gut Microbiota ◽

Magnetic Stimulation ◽

Bacterial Species ◽

Hospital Setting ◽

Personal Genome ◽

Microbiota Composition ◽

Fecal Samples ◽

Gut Microbiota Composition

Growing evidence highlights the crucial role of gut microbiota in affecting different aspects of obesity. Considering the ability of deep transcranial magnetic stimulation (dTMS) to modulate the cortical excitability, the reward system, and, indirectly, the autonomic nervous system (ANS), we hypothesized a potential role of dTMS in affecting the brain-gut communication pathways, and the gut microbiota composition in obesity. In a hospital setting, 22 subjects with obesity (5 M, 17 F; 44.9 ± 2.2 years; BMI 37.5 ± 1.0 kg/m2) were randomized into three groups receiving 15 sessions (3 per week for 5 weeks) of high frequency (HF), low frequency (LF) dTMS, or sham stimulation. Fecal samples were collected at baseline and after 5 weeks of treatment. Total bacterial DNA was extracted from fecal samples using the QIAamp DNA Stool Mini Kit (Qiagen, Italy) and analyzed by a metagenomics approach (Ion Torrent Personal Genome Machine). After 5 weeks, a significant weight loss was found in HF (HF: −4.1 ± 0.8%, LF: −1.9 ± 0.8%, sham: −1.3 ± 0.6%, p = 0.042) compared to LF and sham groups, associated with a decrease in norepinephrine compared to baseline (HF: −61.5 ± 15.2%, p < 0.01; LF: −31.8 ± 17.1%, p < 0.05; sham: −35.8 ± 21.0%, p > 0.05). Furthermore, an increase in Faecalibacterium (+154.3% vs. baseline, p < 0.05) and Alistipes (+153.4% vs. baseline, p < 0.05) genera, and a significant decrease in Lactobacillus (−77.1% vs. baseline, p < 0.05) were found in HF. Faecalibacterium variations were not significant compared to baseline in the other two groups (LF: +106.6%, sham: +27.6%; p > 0.05) as well as Alistipes (LF: −54.9%, sham: −15.1%; p > 0.05) and Lactobacillus (LF: −26.0%, sham: +228.3%; p > 0.05) variations. Norepinephrine change significantly correlated with Bacteroides (r2 = 0.734; p < 0.05), Eubacterium (r2 = 0.734; p < 0.05), and Parasutterella (r2 = 0.618; p < 0.05) abundance variations in HF. In conclusion, HF dTMS treatment revealed to be effective in modulating gut microbiota composition in subjects with obesity, reversing obesity-associated microbiota variations, and promoting bacterial species representative of healthy subjects with anti-inflammatory properties.

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Modifying the Gut Microbiome Through Diet or Antibiotics Alters Bone Phenotypes in Older Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzab054_039 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1184-1184

Author(s):

Kelsey Smith ◽

Macy Castaneda ◽

Chia-Fang Tsai ◽

Sarah Francisco ◽

Jacob Nixon ◽

...

Keyword(s):

Gut Microbiota ◽

Bone Tissue ◽

Bone Strength ◽

Antibiotic Treatment ◽

Gut Microbiome ◽

Bone Geometry ◽

The Other ◽

Oral Antibiotic ◽

Tissue Quality ◽

Section Modulus

Abstract Objectives Gut microbiota have been shown to influence bone quality and quantity, both risk determinants for osteoporosis. Previous research in young mice showed oral antibiotic treatment during rapid bone gain impaired bone tissue quality. We sought to determine if modifying the gut microbiome of aged mice through diet or antibiotic treatment affects bone geometry and/or strength. Methods A high (HG) or low glycemic (LG) diet was fed in equal amounts to 12-mo. male mice. The diets differed only by starch composition, which was 100% rapidly digested amylopectin in the HG diet or 30% amylopectin/70% amylose in the LG diet. A third group received the LG diet containing antibiotics (ampicillin and neomycin; LGAbx). Feces were collected at baseline and after 10 months of treatment and 16s rRNA sequencing was performed followed by ecological diversity and differential abundance analysis. Femora were harvested after 12 months of treatment for analysis of bone geometry and strength via mechanical testing and imaging. Results Antibiotic treatment reduced alpha diversity, including an average 92% reduction in observed OTUs from baseline compared with 30% reduction in the other groups. Both diet and antibiotic treatment significantly altered taxonomic composition, including an expansion of Proteobacteria in response to antibiotics. Whole bone strength is determined by a combination of the section modulus (the measure of geometry most closely related to bending strength) and the mechanical properties of the bone tissue itself. In HG-fed mice the section modulus was greater than that of the other groups and the bone showed a correspondingly greater strength. However, in LGAbx-fed mice the whole bone strength was 22% lower than bones with similar section modulus in the LG and HG-fed groups, indicating impaired bone tissue material properties. Conclusions Altering diet resulted in significant changes to bone geometry and strength, while changes in the gut microbiota associated with antibiotic treatment resulted in a reduction to bone strength which could not be explained by bone geometry. Our study indicates that dietary or antibiotics treatments applied to mice later in life can alter bone properties, which suggests that interventions to improve bone strength may be effective in older adults. Funding Sources NIH/NIAMS, BrightFocus Foundation, Stanley N. Gershoff Scholarship.

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Abstract P174: Sex Differences In The Pro-hypertensive Effect Of Carnitine, The Precursor Of Gut-derived Metabolite TMAO

Hypertension ◽

10.1161/hyp.78.suppl_1.p174 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Justine M Abais-Battad ◽

John Henry Dasinger ◽

David L Mattson

Keyword(s):

Gut Microbiota ◽

Antibiotic Treatment ◽

Renal Damage ◽

Elevated Pressure ◽

High Salt ◽

Male Rats ◽

Oral Antibiotic ◽

Gut Inflammation ◽

Reduced Salt ◽

Salt Sensitive Hypertension

Recent evidence reports sexually divergent mechanisms that differentially drive the severity of hypertension. Our data show that female Dahl Salt-Sensitive (SS) rats are significantly protected from salt-induced hypertension and renal injury and have stark differences in gut microbiota composition compared to males. Gut-derived metabolites are increasingly being recognized as mechanistic links between the gut microbiota and hypertension. One such metabolite is trimethylamine N-oxide (TMAO), which is derived from the bacterial metabolism of carnitine and is gaining notoriety for its role in cardiovascular disease. Metabolomics analysis in high salt-fed SS rats revealed a trend for increased TMAO (1.3-fold, p=0.11) in the serum of males compared to females (n=6). TMAO appears to be specifically derived from gut bacteria since oral antibiotic treatment nearly eliminated circulating TMAO levels in both males and females (99.3% and 88.9% reduction, respectively; p<0.001). Interestingly, antibiotic treatment reduced salt-sensitive hypertension in males but not females. There was also a corresponding increase in the TMAO precursor carnitine (1.9-fold, p<0.01) in the serum of males versus females. Thus, we hypothesized that administration of carnitine (400 mg/kg/day) in the drinking water would exacerbate salt-sensitive hypertension, renal damage, and gut inflammation in male and female SS rats challenged with high salt (4% NaCl). There was a trend for carnitine treatment to exacerbate mean arterial pressure in both males (160±9 vs 146±2 mmHg, n=4-6, p=0.22) and females (155±6 vs 139±2 mmHg, n=2, p=0.14) compared to vehicle. Despite elevated pressure in both sexes, carnitine-treated males exhibited greater increases in albuminuria (340±136 vs 194±29 mg/day, carnitine vs vehicle, p=0.28) than females (55±33 vs 26±5 mg/day). Carnitine treatment also significantly increased the number of CD3+ T cells in the colonic lamina propria (24.3±6.0 vs 2.4±0.5 x 10 6 cells/g tissue, n=5, p<0.05) of male rats compared to vehicle. Together, these data identify gut microbiota-mediated carnitine/TMAO metabolism as a potentially detrimental pathway that promotes greater salt-sensitivity, renal damage, and gut inflammation in males versus females.

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Long-Lasting Effects of Early-Life Antibiotic Treatment and Routine Animal Handling on Gut Microbiota Composition and Immune System in Pigs

PLoS ONE ◽

10.1371/journal.pone.0116523 ◽

2015 ◽

Vol 10 (2) ◽

pp. e0116523 ◽

Cited By ~ 44

Author(s):

Dirkjan Schokker ◽

Jing Zhang ◽

Stéphanie A. Vastenhouw ◽

Hans G. H. J. Heilig ◽

Hauke Smidt ◽

...

Keyword(s):

Immune System ◽

Gut Microbiota ◽

Antibiotic Treatment ◽

Early Life ◽

Microbiota Composition ◽

Animal Handling ◽

Gut Microbiota Composition

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Prebiotic supplementation over a cold season and during antibiotic treatment specifically modulates the gut microbiota composition of 3-6 year-old children

Beneficial Microbes ◽

10.3920/bm2018.0116 ◽

2019 ◽

Vol 10 (3) ◽

pp. 253-263 ◽

Cited By ~ 7

Author(s):

S. Soldi ◽

S. Vasileiadis ◽

S. Lohner ◽

F. Uggeri ◽

E. Puglisi ◽

...

Keyword(s):

Gut Microbiota ◽

Antibiotic Treatment ◽

Relative Abundance ◽

Cold Season ◽

Medical Attention ◽

Control Group ◽

Rrna Gene ◽

Healthy Children ◽

Microbiota Composition ◽

Gut Microbiota Composition

Supplementing kindergarten children during a cold season with a prebiotic inulin-type fructans product with shorter and longer fructan chains has been shown to reduce febrile episodes requiring medical attention and to lower the incidence of sinusitis. These beneficial effects may be connected to the specific modulation of children’s gut microbiota. By applying quantitative and qualitative microbiota analysis this study aimed at characterising the gut microbiota composition and at exploring effects of prebiotic intervention on the gut microbiota during a 24-weeks intervention and during antibiotic treatment in healthy children. The study was a randomised, placebo-controlled trial with 258 healthy children aged 3 to 6 years consuming 6 g/day prebiotic inulin-type fructans or maltodextrin. During the course of the study, faecal samples were collected and subject to targeted qPCR analysis and phylogenetic profiling by multiplexed high throughput sequencing of the prokaryotic 16S rRNA gene PCR amplicons. The microbiota composition of the cohort could be clustered into three distinct constellations (enterotypes). Prebiotic intake resulted in a selective modulation of the gut microbiota composition. Relative abundance of Bifidobacterium was significantly higher in the prebiotic group (n=104) compared to control group (n=105) and this effect was found for all three enterotypes. Antibiotic administration decreased the relative abundance of Bifidobacterium in both groups. Nonetheless, children of the prebiotic group receiving antibiotic treatment displayed significantly higher levels of Bifidobacterium than children receiving the placebo control. Prebiotic supplementation induced specific changes in the gut microbiota composition of children aged 3 to 6 years. Moreover, it attenuated antibiotic-induced disturbances in the gut microbiota composition as shown by higher relative abundance of bifidobacteria at the end of the antibiotic treatment in the prebiotic group. With the previously reported benefits on immune function, the study contributes to the evidence on the immune-modulating effects of prebiotics through gut microbiota modifications. The study was registered as NCT03241355 ( https://clinicaltrials.gov/show/NCT03241355 ).

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