Acute and long-term effects of antibiotics commonly used in laboratory animal medicine on the fecal microbiota

Abstract Biomedical research relies on the use of animal models, and the animals used in those models receive medical care, including antibiotics for brief periods of time to treat conditions such as dermatitis, fight wounds, and suspected bacterial pathogens of unknown etiology. As many mouse model phenotypes are sensitive to changes in the gut microbiota, our goal was to examine the effect of antibiotics commonly administered to mice. Therefore, four treatment groups (subcutaneous enrofloxacin for 7 days, oral enrofloxacin for 14 days, oral trimethoprim-sulfamethoxazole for 14 days, and topical triple antibiotic ointment for 14 days) alongside a fifth control group receiving no treatment (n = 12/group) were included in our study. Fecal samples were collected prior to treatment, immediately after two weeks of exposure, and four weeks after cessation of treatment, and subjected to 16S rRNA library sequencing. The entire experimental design was replicated in mice from two different suppliers. As expected, several treatments including enrofloxacin and triple antibiotic ointment substantially decreased the amount of DNA recovered from fecal material, as well as the microbial richness. Notably, many of these effects were long-lasting with diminished gut microbiota (GM) richness four weeks following exposure, in both substrains of mice. Trimethoprim-sulfamethoxazole induced minimal to no discernible changes in the taxonomic composition beyond that seen in control mice. Collectively, these data highlight the need to consider the impact on GM of brief and seemingly routine use of antibiotics in the clinical care of research animals.

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Modulation of Gut Microbiota and Oxidative Status by β-Carotene in Late Pregnant Sows

Frontiers in Nutrition ◽

10.3389/fnut.2020.612875 ◽

2020 ◽

Vol 7 ◽

Author(s):

Xupeng Yuan ◽

Jiahao Yan ◽

Ruizhi Hu ◽

Yanli Li ◽

Ying Wang ◽

...

Keyword(s):

Gut Microbiota ◽

Dietary Supplementation ◽

Basal Diet ◽

Fecal Microbiota ◽

Control Group ◽

Metabolic Activities ◽

The Impact ◽

Positive Effect ◽

Β Carotene

Recent evidences suggest that gut microbiota plays an important role in regulating physiological and metabolic activities of pregnant sows, and β-carotene has a potentially positive effect on reproduction, but the impact of β-carotene on gut microbiota in pregnant sows remains unknown. This study aimed to explore the effect and mechanisms of β-carotene on the reproductive performance of sows from the aspect of gut microbiota. A total of 48 hybrid pregnant sows (Landrace × Yorkshire) with similar parity were randomly allocated into three groups (n = 16) and fed with a basal diet or a diet containing 30 or 90 mg/kg of β-carotene from day 90 of gestation until parturition. Dietary supplementation of 30 or 90 mg/kg β-carotene increased the number of live birth to 11.82 ± 1.54 and 12.29 ± 2.09, respectively, while the control group was 11.00 ± 1.41 (P = 0.201). Moreover, β-carotene increased significantly the serum nitric oxide (NO) level and glutathione peroxidase (GSH-Px) activity (P < 0.05). Characterization of fecal microbiota revealed that 90 mg/kg β-carotene increased the diversity of the gut flora (P < 0.05). In particular, β-carotene decreased the relative abundance of Firmicutes including Lachnospiraceae AC2044 group, Lachnospiraceae NK4B4 group and Ruminococcaceae UCG-008, but enriched Proteobacteria including Bilophila and Sutterella, and Actinobacteria including Corynebacterium and Corynebacterium 1 which are related to NO synthesis. These data demonstrated that dietary supplementation of β-carotene may increase antioxidant enzyme activity and NO, an important vasodilator to promote the neonatal blood circulation, through regulating gut microbiota in sows.

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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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Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽

10.3390/biomedicines9020145 ◽

2021 ◽

Vol 9 (2) ◽

pp. 145

Author(s):

Julio Plaza-Díaz ◽

Patricio Solis-Urra ◽

Jerónimo Aragón-Vela ◽

Fernando Rodríguez-Rodríguez ◽

Jorge Olivares-Arancibia ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Liver Steatosis ◽

Intestinal Barrier ◽

Fecal Microbiota ◽

Current Treatment ◽

Immune Defense ◽

Alcoholic Fatty Liver ◽

The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

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

Microbiome ◽

10.1186/s40168-021-01088-9 ◽

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.

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Abstract 1818: Beneficial Effects of Weight Loss Associated with a High Protein Diet on Cardiovascular Risk Profile, Functional Status and Quality of Life in Obese Heart Failure Patients: A Feasibility Study

Circulation ◽

10.1161/circ.116.suppl_16.ii_387-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Lorraine S Evangelista ◽

David Heber ◽

Zhaoping Li ◽

Michele Hamilton ◽

Gregg C Fonarow

Keyword(s):

Heart Failure ◽

Weight Loss ◽

Body Weight ◽

Functional Status ◽

High Protein ◽

Control Group ◽

Long Term Effects ◽

Weight Changes ◽

Cardiovascular Risks ◽

The Impact

OBJECTIVE: Clinical management of chronic heart failure (HF) related to adequate nutritional intake currently lacks a strong scientific basis. This study was conducted to evaluate the impact of 3 diet interventions on body weight and its potential to reduce cardiovascular risks and improve functional status. METHOD: Fourteen obese HF patients (BMI > 27 kg/m2) were randomized to1 of 3 diets: high protein (HP); low fat (LF) or average diet/control group (CG). Body anthropometrics (weight, BMI, waist circumference), indices of cardiovascular risks including (% body fat, blood pressure, cholesterol, triglycerides), and measures of functional status (6-minute walk, max VO2) were obtained at baseline and after a 12-week nutritional support program. Statistics included two-way RMANOVA. RESULTS: There were no significant differences in age (59±10 years), gender (78% male), NYHA (43% class II; 57% class III), HF etiology (57% non-ischemic), or ejection fraction (0.26±0.07) between the groups. The HP diet resulted in moderate reductions in body weight (Figure ) and improvements in several health parameters (Table ). CONCLUSION: The data show that in a small group of obese HF patients, a 12-week HP diet resulted in moderate weight loss that was associated with reduced cardiovascular risks and better functional status. However, the long-term effects of a HP diet remain uncertain. Figure Comparison of Weight Changes in the HP, LF and CG from Baseline to 12 Weeks Mean changes in outcomes from baseline to 12 weeks, by diet group and time

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The impact of human-facilitated selection on the gut microbiota of domesticated mammals

FEMS Microbiology Ecology ◽

10.1093/femsec/fiz121 ◽

2019 ◽

Vol 95 (9) ◽

Cited By ~ 8

Author(s):

Giulia Alessandri ◽

Christian Milani ◽

Leonardo Mancabelli ◽

Marta Mangifesta ◽

Gabriele Andrea Lugli ◽

...

Keyword(s):

Gut Microbiota ◽

Horizontal Transmission ◽

Taxonomic Composition ◽

Functional Adaptation ◽

Rrna Gene ◽

Feed Conversion ◽

Shotgun Metagenomics ◽

Domesticated Animals ◽

And Behavior ◽

The Impact

ABSTRACT Domestication is the process by which anthropogenic forces shape lifestyle and behavior of wild species to accommodate human needs. The impact of domestication on animal physiology and behavior has been extensively studied, whereas its effect on the gut microbiota is still largely unexplored. For this reason, 16S rRNA gene-based and internal transcribed spacer-mediated bifidobacterial profiling, together with shotgun metagenomics, was employed to investigate the taxonomic composition and metabolic repertoire of 146 mammalian fecal samples, corresponding to 12 domesticated–feral dyads. Our results revealed that changes induced by domestication have extensively shaped the taxonomic composition of the mammalian gut microbiota. In this context, the selection of microbial taxa linked to a more efficient feed conversion into body mass and putative horizontal transmission of certain bacterial genera from humans were observed in the fecal microbiota of domesticated animals when compared to their feral relatives and to humans. In addition, profiling of the metabolic arsenal through metagenomics highlighted extensive functional adaptation of the fecal microbial community of domesticated mammals to changes induced by domestication. Remarkably, domesticated animals showed, when compared to their feral relatives, increased abundance of specific glycosyl hydrolases, possibly due to the higher intake of complex plant carbohydrates typical of commercial animal feeds.

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2579. Impact on the Gut Microbiota of the Prolonged Antimicrobial Therapy in Patients with Bone and Joint Infection (BJI): Results From the OSIRIS Prospective Study in France

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.2257 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S896-S896

Author(s):

Benoit Levast ◽

Cécile Batailler ◽

Cécile Pouderoux ◽

Lilia Boucihna ◽

Sébastien Lustig ◽

...

Keyword(s):

Gut Microbiota ◽

Fecal Microbiota Transplantation ◽

Joint Infection ◽

Surrogate Marker ◽

Generation Cephalosporin ◽

Fecal Microbiota ◽

Metagenomic Sequencing ◽

Gut Dysbiosis ◽

Prosthetic Joint ◽

The Impact

Abstract Background There is growing interest about the deleterious impact of antibiotics on loss of gut symbiosis, called dysbiosis. As patients with BJI require antibiotics usually during 6 to 12 weeks, it is of interest to determine whether dysbiosis is frequent in this population, and if it could potentially reversible or not. Methods Multicentric prospective cohort study in France (EudraCT 2016-003247-10) including patients with 3 categories of BJI: native, osteosynthesis-related and prosthetic joint infection (PJI). At the time of suspicion (V1), at the end of therapy (V2) and then 2 weeks after stopping therapy (V3), blood and fecal samples were collected. Extracted DNA from stool was sequenced using shotgun metagenomic sequencing based on illumina library and Iseq instrumentation. Data run through a dedicated pipeline in order to produce microbiome indexes such as Sympson or Shannon diversities indexes. Gut microbiome and inflammation markers were analyzed including fecal neopterin, a maker of gut inflammation. Results Concerning the 62 patients included (mean age, 60 years; mean duration of antibiotics, 66 days), 27 had native, 14 had osteosynthesis and 21 had PJI. The most frequently prescribed drug was a fluoroquinolone, followed by a third-generation cephalosporin and vancomycin. Stools from 42 of them were analyzed as per protocol. Overall, the mean Shannon richness index decreased from 0.904 at V1 to 0.845 at V2; the Bray-Curtis index underlined the difference in microbiome reconstitution at V3 in comparison with V1. We report significant microbiome loss of diversity at V2, that was reversible at V3 in patients with native BJI and osteosynthesis-related BJI, but not in patients with PJI (figure). Fecal neopterin increased between V1 and V2 (mean 221.6 and 698.1 pmol/g of feces, respectively) and then decreased at V3 (422.5 pmol/g), and could be a potential surrogate marker of gut dysbiosis. Of note, patients with abnormal CRP at the end of antibiotics had high neopterin values, that raises the hypothesis that abnormal CRP at the end of antibiotics could be in relation with gut dysbiosis rather than uncured BJI. Conclusion The impact of antibiotics on the gut microbiota of patients with BJI seems to be significant, especially in patients with PJI who could be candidate for fecal microbiota transplantation. Disclosures All authors: No reported disclosures.

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Environmental Influences on the Human Gut Microbiota: A Longitudinal Pilot Study

Current Developments in Nutrition ◽

10.1093/cdn/nzab054_006 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 1151-1151

Author(s):

Marina Brown ◽

Ginger Reeser ◽

Leila Shinn ◽

Matthew Browning ◽

Andiara Schwingel ◽

...

Keyword(s):

Gut Microbiota ◽

Dietary Habits ◽

Pilot Trial ◽

Alpha Diversity ◽

Total Sample ◽

Fecal Microbiota ◽

Healthy Eating Index ◽

Garden Soil ◽

Control Group ◽

Soil Dna

Abstract Objectives Urbanization has reduced environmental microorganism exposure, with most Americans spending over 90% of their time indoors. However, gardening remains a viable means of exposure to soil microorganisms and harvesting of edible produce. Accordingly, we aimed to determine relations between gardening, dietary habits, and gut microbiota. Methods Gardening families (N = 10) and non-gardening (control) families (N = 9) were enrolled in a longitudinal pilot trial. Families included two adults and a child (5–18 years) for a total sample size of 54 participants. Fecal samples were collected prior to and at the end of the gardening season. Garden soil samples (n = 9) were collected prior to and at the end of the season. Diet history questionnaires were collected at the beginning and end of the study to measure Healthy Eating Index (HEI) scores. Fecal and soil DNA were extracted, sequenced (V4 region of 16S rDNA gene), and analyzed using DADA2 and QIIME2. Alpha diversity measures were assessed, including Faith's phylogenetic diversity (PD) and observed operational taxonomic units (OTUs). Results Gardening families had significantly more fecal OTUs compared to control families (172.3 ± 44.2 vs. 157.0 ± 44.2, respectively; P = 0.03). Gardening families had greater (P = 0.02) Faith's PD scores and tended (P = 0.08) to have more fecal OTUs than the control group at peak gardening season. In the gardening families, fecal OTUs and Faith's PD were numerically but not statistically greater at the end of the season compared to baseline (all p’s > 0.05). Prior to the gardening season, gardening adults had greater HEI scores compared to control families (57 ± 9.1 vs. 49 ± 8.8, P = 0.03). HEI scores were not different between groups at the end of the study. Conclusions This study revealed that the fecal microbiota of families that garden differs from non-gardening families, and there are detectable changes in the fecal microbial community of gardeners and their family members over the course of the gardening season. Further research is needed to understand the role of diet in these changes and if microbes within the soil move between the soil and gastrointestinal environments. Funding Sources This research was funded by the Christopher Family Foundation Food and Family Grant Program.

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Using Health Information Technology to Engage African American Women on Nutrition and Supplement Use During the Preconception Period

Frontiers in Endocrinology ◽

10.3389/fendo.2020.571705 ◽

2021 ◽

Vol 11 ◽

Author(s):

Paula Gardiner ◽

Timothy Bickmore ◽

Leanne Yinusa-Nyahkoon ◽

Matthew Reichert ◽

Clevanne Julce ◽

...

Keyword(s):

African American ◽

African American Women ◽

Health Risks ◽

Preconception Care ◽

Clinical Care ◽

Stage Of Change ◽

Control Group ◽

Conversational Agent ◽

Supplement Use ◽

The Impact

ImportanceHealthy nutrition and appropriate supplementation during preconception have important implications for the health of the mother and newborn. The best way to deliver preconception care to address health risks related to nutrition is unknown.MethodsWe conducted a secondary analysis of data from a randomized controlled trial designed to study the impact of conversational agent technology in 13 domains of preconception care among 528 non-pregnant African American and Black women. This analysis is restricted to those 480 women who reported at least one of the ten risks related to nutrition and dietary supplement use.InterventionsAn online conversational agent, called “Gabby”, assesses health risks and delivers 12 months of tailored dialogue for over 100 preconception health risks, including ten nutrition and supplement risks, using behavioral change techniques like shared decision making and motivational interviewing. The control group received a letter listing their preconception risks and encouraging them to talk to a health care provider.ResultsAfter 6 months, women using Gabby (a) reported progressing forward on the stage of change scale for, on average, 52.9% (SD, 35.1%) of nutrition and supplement risks compared to 42.9% (SD, 35.4) in the control group (IRR 1.22, 95% CI 1.03–1.45, P = 0.019); and (b) reported achieving the action and maintenance stage of change for, on average, 52.8% (SD 37.1) of the nutrition and supplement risks compared to 42.8% (SD, 37.9) in the control group (IRR 1.26, 96% CI 1.08–1.48, P = 0.004). For subjects beginning the study at the contemplation stage of change, intervention subjects reported progressing forward on the stage of change scale for 75.0% (SD, 36.3%) of their health risks compared to 52.1% (SD, 47.1%) in the control group (P = 0.006).ConclusionThe scalability of Gabby has the potential to improve women’s nutritional health as an adjunct to clinical care or at the population health level. Further studies are needed to determine if improving nutrition and supplement risks can impact clinical outcomes including optimization of weight.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT01827215.

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Colonization of Supplemented Bifidobacterium breve M-16V in Low Birth Weight Infants and Its Effects on Their Gut Microbiota Weeks Post-administration

Frontiers in Microbiology ◽

10.3389/fmicb.2021.610080 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ayako Horigome ◽

Ken Hisata ◽

Toshitaka Odamaki ◽

Noriyuki Iwabuchi ◽

Jin-zhong Xiao ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Gut Microbiota ◽

16S Rrna Gene Sequencing ◽

Fecal Microbiota ◽

Control Group ◽

Rrna Gene ◽

Low Birth Weight Infants ◽

Fecal Samples ◽

Bifidobacterium Breve

The colonization and persistence of probiotics introduced into the adult human gut appears to be limited. It is uncertain, however, whether probiotics can successfully colonize the intestinal tracts of full-term and premature infants. In this study, we investigated the colonization and the effect of oral supplementation with Bifidobacterium breve M-16V on the gut microbiota of low birth weight (LBW) infants. A total of 22 LBW infants (12 infants in the M-16V group and 10 infants in the control group) were enrolled. B. breve M-16V was administrated to LBW infants in the M-16V group from birth until hospital discharge. Fecal samples were collected from each subject at weeks (3.7–9.3 weeks in the M-16V group and 2.1–6.1 weeks in the control group) after discharge. qPCR analysis showed that the administrated strain was detected in 83.3% of fecal samples in the M-16V group (at log10 8.33 ± 0.99 cell numbers per gram of wet feces), suggesting that this strain colonized most of the infants beyond several weeks post-administration. Fecal microbiota analysis by 16S rRNA gene sequencing showed that the abundance of Actinobacteria was significantly higher (P < 0.01), whereas that of Proteobacteria was significantly lower (P < 0.001) in the M-16V group as compared with the control group. Notably, the levels of the administrated strain and indigenous Bifidobacterium bacteria were both significantly higher in the M-16V group than in the control group. Our findings suggest that oral administration of B. breve M-16V led to engraftment for at least several weeks post-administration and we observed a potential overall improvement in microbiota formation in the LBW infants’ guts.

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