[Nutrition and mental health in athletes]. / Nutrition et santé mentale des athlètes.

In the world of top-level sport, optimising athletic performance does not rely solely on physical training. Taking into account the intestine-brain axis offers new ways of optimising sports preparation, partly thanks to the role of the intestinal microbiota on performance and well-being.

The effect of Escherichia coli ZP strain with a conjugation-based colicin E7 delivery on growth performance, hematological, biochemical, and histological parameters, gut microbiota, and nonspecific immunity of broilers.

The Escherichia coli ZP strain (ZP) was constructed based on the known probiotic E. coli strain Nissle 1917. It was genetically modified to carry the colicin E7 synthesis gene encoding DNase on a conjugative plasmid and the colicin E7 immunity gene in the chromosome. The aim of this study was to evaluate the effects of the daily ZP per oral administration (5 × 108 or 5 × 1010 CFU per bird) on the growth performance, hematological, biochemical, histological parameters, gut microbiota, and nonspecific immunity of the 4-24 days old broilers. The ZP administration increased the abundance of genera Bacillus, Butyrivibrio, and Clostridium and did not influence the weight gain of 4-16 days old broilers. The biochemical parameters were within normal ranges for poultry in experimental and control groups. The ZP administration had no effect on the erythrocyte numbers, hemoglobin and immunoglobulin Y concentrations, but significantly increased the serum lysozyme concentration, leukocyte numbers, and reactive oxygen species production by phagocytes compared with the control group. It did not cause inflammatory changes in intestinal mucosa, Peyer's patches, and spleen. Thus, the ZP had no detrimental effects on broiler health and could be an efficient probiotic for the broiler colibacillosis prophylaxis.

Association Between Gut Microbiota and Insulin Therapy in Women With Gestational Diabetes Mellitus.

OBJECTIVES: At the time of diagnosis, the blood glucose of women with gestational diabetes mellitus (GDM) who require subsequent insulin treatment does not differ from that of women with adequate diet control. Hence, in this study, we aimed to determine the role of maternal gut microbiota as a marker of insulin necessity in GDM and to identify the effect of insulin therapy on gut microbiota composition in mothers with GDM and their newborns. METHODS: Seventy-one pregnant women were enrolled into the study, including 38 GDM and 33 non-GDM participants. During the follow-up period, 8 of the 38 GDM subjects required insulin therapy (GDM-I group), whereas 30 of the 38 GDM cases with sufficient glycemic control by diet alone (GDM-D group). Maternal blood and feces were obtained at the time of GDM diagnosis (pretreatment; 24 to 28 weeks of gestation) and before delivery (posttreatment; ≥37 weeks of gestation). Meconium and first feces of the newborns were also collected. RESULTS: Pretreatment, the glycemic profile did not differ between the GDM-D and GDM-I groups. However, the proportions of Clostridiales, Lactobacillus and Bacteroidetes were higher in the GDM-I group than in the non-GDM and GDM-D groups. After treatment, gut microbiota composition showed no difference between non-GDM and GDM-I groups. Interestingly, a higher Firmicutes/Bacteroidetes (F/B) ratio was displayed in GDM-D mothers at posttreatment, and this was also observed in both meconium and first feces of GDM-D newborns. CONCLUSION: Insulin therapy changed maternal gut microbiota composition, which could be transferable to the mothers' newborns.

Trimethylamine N-oxide promotes hyperlipidemia acute pancreatitis via inflammatory response.

Trimethylamine N-oxide (TMAO), a metabolite of gut microbiota, is involved in the regulation of lipid metabolism and inflammatory response; however, the role of TMAO in hyperlipidemia acute pancreatitis (HAP) is not clear. In this study, HAP mice were used as an animal model to explore the effects and possible mechanism of TMAO on HAP, which may provide new ideas for the treatment of HAP. Results found that the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, nonestesterified fatty acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, α-amylase, TMAO, and flavin-containing monooxygenase 3 were significantly increased, the levels of high-density lipoprotein cholesterol and insulin were significantly decreased, and there was an obvious pancreatic injury and inflammatory response in the model group. The choline analogue 3,3-dimethyl-1-butanol (DMB) treatment reversed the changes of serum biochemical parameters, alleviated the pancreatic tissue injury, and reduced the levels of inflammatory cytokines. Further studies of toll-like receptor (TLR)/p-glycoprotein 65 (p65) pathway found that the expressions of TLR2, TLR4, and p-p65/p65 in the model group were significantly increased, which was more obvious after Escherichia coli (Migula) Castellani & Chalmers treatment, while activation of the TLR/p65 pathway was inhibited by DMB. The results indicated that TMAO promotes HAP by promoting inflammatory response through TLR/p65 signaling pathway, suggesting that TMAO may be a potential target of HAP.

Green banana flour supplementation improves obesity-associated systemic inflammation and regulates gut microbiota profile in mice fed high-fat diets.

This study evaluated the effect of green banana flour (GBF) consumption on obesity-related conditions in mice fed high-fat diets. GBF was prepared using stage 1 green banana pulp, which was dehydrated and milled. Mice were fed a control diet (n = 20; 10% of energy from lipids) or a high-fat diet (n = 20; 50% of energy from lipids). After 10 weeks, mice were divided into 4 groups based on feed: standard chow (SC; n = 10), standard with 15% GBF (SB; n = 10), high-fat diet (HF; n = 10) and high-fat diet with 15% GBF (HFB; n = 10) for 4 weeks. HFB exhibited lower gains in body weight (-21%; p < 0.01) and in all fat pads (p < 0.01) compared with the HF group. SC, SB, and HFB showed smaller retroperitoneal white adipose tissue diameters (p < 0.001). SB and HFB-treated mice showed lower levels of leptin, IL-6, and TNF-α compared with the SC and HF groups (p < 0.01). In the GBF-fed groups, there was a reduction in the abundance of Firmicutes (SB: -22%; HFB: -23%) and an increase in Bacteroidetes (SB: +25%; HFB: +29%) compared with their counterparts. We demonstrated that GBF consumption attenuated inflammation and improved metabolic status, adipose tissue remodeling, and the gut microbiota profile of obese mice. Novelty: Green banana flour (GBF) consumption, rich in resistant starch, regulates body weight in mice fed high-fat diets. GBF consumption improves fat pad distribution in mice fed high-fat diets. GBF improves obesity-associated systemic inflammation and regulates gut microbiota profile in mice fed high-fat diets.

Feasibility and effects on the gut microbiota of a 12-week high-intensity interval training plus lifestyle education intervention on inactive adults with celiac disease.

This study assessed the feasibility and benefits of high-intensity interval training (HIIT) plus lifestyle education among inactive adults with celiac disease. Forty-one participants were randomized to receive the intervention (HIIT plus lifestyle education; HIIT+) for 12 weeks or waitlist control (WLC). Testing was completed at baseline, immediately post-intervention, and 3 months post-intervention. Generalized estimating equations were used to assess changes in the outcome variables over time between the groups. Mean percent of age-predicted maximum heart rate was 97.9% and average rating of perceived exertion was 6.33 (out of 10) during HIIT intervals. Following the intervention, the HIIT+ showed enrichment in relative abundance of Parabacteroides and Defluviitaleaceae_UCG_011 while WLC showed enrichment in relative abundance of Roseburia intestinalis, Klebsiella, and Adlercreutzia. A unique set of taxa were differentially abundant between the groups at 3 months post-intervention. HIIT+ participants experienced a reduction in resting heart rate (-6.6 bpm) immediately post-intervention compared with WLC. Further research is needed to establish an optimal HIIT protocol that may improve maximal oxygen uptake and metabolic syndrome biomarkers. Findings from this pilot study provide preliminary evidence that an HIIT intervention is feasible for inactive adults with celiac disease and leads to favourable changes in resting heart rate alongside potentially beneficial shifts in gut microbiota. Trial registration number: ClinicalTrials.gov number NCT03520244. Novelty: HIIT leads to potentially beneficial changes in the gut microbiota of adults with celiac disease. An HIIT exercise intervention is feasible and well tolerated for patients with celiac disease.

Gut microbiota dysbiosis in polycystic ovary syndrome: association with obesity - a preliminary report.

The objective was to explore if and how the microbiota changed in polycystic ovary syndrome (PCOS) women compared with healthy women. Eight obese PCOS (PO group), 10 nonobese PCOS (PN group), and nine healthy normal weight women (control) (C group) were enrolled. Insulin (INS), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), and dehydroepiandrosterone (DHEA) were detected with radioimmunoassay. Antimullerian hormone (AMH), fasting glucose, and hemoglobin A1c (HbA1c) were determined by a chemiluminescence immunoassay, glucose oxidase method, and HPLC, respectively. Gut microbiota composition was evaluated by PCR. Alpha diversity was assessed using Chao1 and the Shannon index. PCOS women showed significantly higher T, LH, and LH/FSH and lower FSH levels than the C group (p < 0.05). The AMH level was significantly higher in the PO than in the PN group (p < 0.05). The PO group presented a significantly higher fasting INS level and HMOA-IR scores than the other groups, lower observed SVs and alpha diversity than the C group, higher beta diversity than the PN group (p < 0.05), and decreased abundances of genera (mainly butyrate producers). Regression analysis showed that decreased abundances of several genera were correlated with higher circulating T and impaired glucose metabolism. PCOS is associated with changes in the gut microbiota composition. Obesity has a driving role in the development of dysbiotic gut microbiota in PCOS.

Interplay Between Gut Microbiota and Gastrointestinal Peptides: Potential Outcomes on the Regulation of Glucose Control.

A host of gastrointestinal (GI) peptides influence the regulation of vital functions, such as growth, appetite, stress, gut motility, energy expenditure, digestion and inflammation, as well as glucose and lipid homeostasis. Hence, impairments in the synthesis/secretion of glucagon-like peptide-1 (GLP-1), leptin, nesfatin-1, glucose-dependent insulinotropic peptide (GIP), ghrelin (acylated and unacylated forms), oxyntomodulin, vasoactive intestinal peptide, somatostatin, cholecystokinin, peptide tyrosine‒tyrosine, GLP-2 and pancreatic polypeptide were previously associated with the development of obesity-related disorders. It is currently emphasized that the beneficial metabolic outcomes associated with the normalization of the gut microbiota (GM) is influenced by increases in GLP-1 and peptide YY secretion as well as by decreases in acylated ghrelin production. These effects are associated with reductions in body weight and adiposity in combination with the normalization of glucose and lipid metabolism. However, important questions remain unanswered regarding how GLP-1, peptide tyrosine‒tyrosine, acylated ghrelin and other metabolically relevant GI peptides interact with the GM to modulate the host's metabolic functions. In addition, it is likely that the GM and other biologically active GI peptides influence metabolic functions, such as glucose control, although the mechanisms remain ill-defined. In this review, we investigate how GM and GI peptides influence glucose metabolism in experimental models, such as germ-free animals and dietary interventions. Emphasis is placed on pathways through which GM and GI peptides could modulate intestinal permeability, nutrient absorption, short-chain fatty acid production, metabolic endotoxemia, oxidative stress and low-grade inflammation.

Changes in Intestinal Microbiota of Type 2 Diabetes in Mice in Response to Dietary Supplementation With Instant Tea or Matcha.

OBJECTIVE: Gut microbiota plays a key role in metabolism and health in diabetes patients with gastrointestinal microbiota dysbiosis. Thus, regulating the ecological balance of gut microbiota may provide a pathway toward improvement for these patients. Our previous study showed that functional ingredients in tea may inhibit cornstarch digestion in vitro. METHODS: A cornstarch-tea diet was developed, and in this study we investigated the effects of such a diet on blood glucose and gut microbiota in diabetic mice. RESULTS: Diabetes resulted in significant weight loss, hyperphagia and hyperglycemia. 16S rDNA sequencing revealed that in diabetes there is significantly increased Bacteroidaceae, Helicobacteraceae, Ruminococcaceae, Enterobacteriaceae, Rikenellaceae and Saccharibacteria_genera_incertae_sedis, and significantly decreased Lactobacillaceae, Prevotellaceae, Coriobacteriaceae, Verrucomicrobiaceae and Bifidobacteriaceae. The cornstarch‒tea diet resulted in a trend toward reduced blood glucose, with particularly increased levels of Coriobacteriaceae, Lactobacillaceae, Prevotellaceae and Bifidobacteriaceae, and decreased Bacteroidaceae, Ruminococcaceae, Helicobacteraceae and Enterobacteriaceae. CONCLUSIONS: Instant tea and matcha supplementation had beneficial effects on regulation of blood glucose and gut microbiota, reversing the changes in microbiota caused by alloxan injection. The cornstarch‒tea regulation pathway is involved in bacterium group regulation rather than single-species regulation, which suggests that cornstarch combined with tea may be used as a functional food supplement for diabetes patients.

[Intestinal microbiota and allogeneic stem cell transplantation]. / Microbiote intestinal et allogreffe de cellules souches hématopoïétiques.

Allogeneic hematopoïetic stem cell transplantation is one of the most efficient curative treatment for acute leukemia. But it is also a heavy process with an important risk of complications, particularly infection and graft versus host disease. Increasing data in literature show that an alteration of the intestinal microbiota of allogeneic stem cell recipients is associated with these complications. Indeed, treatments used during conditioning regimen lead to an impaired microbiota, which cannot fulfill its protective functions anymore. To limit this microbiota impairment, we could restore a healthy microbiota by a fecal microbiota transplantation, which has already shown its efficiency in the treatment of Clostridium difficile infection. The aim of this review is to describe the intestinal microbiota, the link between microbiota and complications of allogeneic stem cells transplantation, and the recent published data on fecal microbiota transplantation in this field.

Pharmacologic and Nonpharmacologic Therapies for the Gut Microbiota in Type 2 Diabetes.

The gut microbiota is an important regulator of host metabolism. Metagenome analyses have demonstrated that the gut microbiota differs between patients with type 2 diabetes and healthy subjects, and several studies have shown that impaired glucose metabolism is associated with decreased levels of butyrate-producing bacteria. Gut microbiota-produced metabolites, such as short-chain fatty acids, amino acid derivatives and secondary bile acids, participate in metabolic and immunologic processes and, hence, pose putative links between the gut microbiota and glucose homeostasis. Strategies to prevent and treat type 2 diabetes through manipulation of the gut microbiota are being developed. These include replacement of the gut microbiota by fecal transplantation, consumption of fibres to promote the function and growth of beneficial bacteria and treatment with probiotic bacterial strains. Furthermore, it has been shown that many drugs, including drugs used for treatment of diabetes, have major impacts on gut microbiota and, thereby, potentially on glucose metabolism. In particular, the commonly used drug metformin has been shown to influence the functional capacity of the gut microbiota, and recent evidence indicates that this may contribute to the antidiabetes effect of metformin.

Reshaping fecal gut microbiota composition by growing with Polygonum cuspidatum, Houttuynia cordata, and Ipomoea aquatica.

We carried out sequencing of samples cultivated in floating beds with different Chinese medicinal herbs (Control, Houttuynia cordata Thunb., Polygonum cuspidatum, and a combination of H. cordata with Ipomoea aquatica Forssk.; named groups A, B, C, D, respectively) to analyze changes in the composition of gut microbiota of tilapia feces. Fusobacteria (ranging from 49.0% to 73.3%), Firmicutes (12.3%-37.8%), and Proteobacteria (5.1%-23.0%) were found to be the most dominant phyla present in all samples. The operational taxonomic units and the Ace and Chao1 indices of groups A and D were significantly higher than those of group C. Polygonum cuspidatum decreased the species richness and diversity of microbial communities in tilapia intestinal feces. The phylum WCHB1-60, order Enterobacteriales, and genus Plesiomonas significantly decreased (in group A); the species Plesiomonas shigelloides significantly decreased (in groups B and C); and the genus Leucobacter significantly increased (in group D) when compared with the control. The relative abundance of the class Verrucomicrobiae (groups B vs C) significantly decreased. In the presence of I. aquatica, the phylum Bacteroidetes significantly decreased, while the genera Leucobacter and Pelotomaculum significantly increased. The ratio of Bacteroidetes to Firmicutes was significantly higher in groups B and C relative to the controls, while it decreased significantly in group D. The algae (i.e., Anabaena and Microcystis) and beneficial pathogenic bacteria decreased in groups C and D, respectively. In addition, Enterovibrio decreased in all treatment groups. The present data demonstrate that floating bed cultivation with Chinese medicinal herbs significantly alters the gut microbiota of tilapia, which may enhance its immune activity.

[What's new in internal medicine?] / Quoi de neuf en médecine interne?

What's new in internal medicine will be dedicated to three topics: i) inflammatory myopathies constituting a heterogenous group of diseases whose clinical manifestations, immunological abnormalities, treatment response and outcomes vary widely; ii) alterations of gut microbiota contributing to the occurrence or development of a range of conditions, including autoimmune diseases for which further work is necessary to understand the correlation of dysbiosis with these diseases; iii) the reciprocal relationship between obesity, metabolic syndrome, atherosclerosis and autoimmune diseases. New data concerning systemic sclerosis, cutaneous vasculitis, adult Still's disease, autoantibodies anti DFS70, Epstein Barr virus and autoimmune diseases were also highlighted.

The impact of the intestinal microbiota in therapeutic responses against cancer.

Accumulating evidence points to the impact of the gut microbiota in regulating various chronic inflammatory disorders such as cancers. The intestinal microbiome is not only influencing the spontaneous course of colon malignancies but also acts at distant sterile sites of neoplasia, mostly playing a detrimental role. By providing microbial-associated molecular patterns and potentially antigens sharing molecular mimicry with tumor antigens, our commensals modulate the local and the systemic immune tonus, eventually influencing tumor microenvironment. Complicating this algorithm, therapeutic interventions alter the delicate balance between the epithelium, the microbial community, and the intestinal immunity, governing the final clinical outcome. This seminar focused on the impact of the intestinal composition on the immunomodulatory and therapeutic activities of distinct compounds (alkylating agents, platinum salts and immunotherapies) used in oncology. This research opens up "the era of anticancer probiotics" aimed at restoring gut eubiosis for a better clinical outcome in cancer patients.

Potential of Lactobacillus plantarum ZDY2013 and Bifidobacterium bifidum WBIN03 in relieving colitis by gut microbiota, immune, and anti-oxidative stress.

Ulcerative colitis (UC) is an inflammatory bowel disease that is difficult to cure, with rising incidence in recent decades. Probiotics have become a new strategy for UC treatment. In this study, we chose 2 new multisource probiotics, Lactobacillus plantarum ZDY2013 from acid beans and Bifidobacterium bifidum WBIN03 from infant feces, and a mixture of both, to investigate the anti-inflammatory and antioxidant effect on H2O2-induced oxidative damage in a HT-29 cell model and dextran sodium sulfate (DSS)-induced UC in mice. Compared with the model group, the general relative indices results showed L. plantarum ZDY2013 and B. bifidum WBIN03 have a significant effect on DSS-induced UC in mice, by downregulating the pro-inflammatory cytokines (e.g., TNF-α) and upregulating antioxidant factors (e.g., SOD1, SOD2, GPX2) at the transcriptional level. By means of high-throughput sequencing (16S V3-V4) and systematical bioinformatics analyses, we found that colitis may be associated with the changes in intestinal flora, especially Firmicutes and Bacteroides. Administration of L. plantarum ZDY2013 increased the abundance of Lactobacillus animalis, whereas B. bifidum WBIN03 increased the abundance of Lachnospiraceae bacterium COE1. Our results revealed that a supplement of L. plantarum ZDY2013 and B. bifidum WBIN03 remit UC through modification of gut microbiota to regulate oxidative stress and inflammatory mediators.

[Gut microbiota: What impact on colorectal carcinogenesis and treatment?] / Le microbiote intestinal : quels impacts sur la carcinogenèse et le traitement du cancer colorectal ?

The gut microbiota, composed of 1014 microorganisms, is now considered as a "hidden organ", regarding to its digestive, metabolic and immune functions, which are helpful to its host. For the last 15 years, advances in molecular biology have highlighted the association of gut microbiota dysbiosis with several diseases, including colorectal cancer. An increased abundance of some bacteria (including Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli) is associated with cancer, whereas others seem to be protective (Faecalibacterium prausnitzii). Several mechanisms, which are species-specific, are involved in colorectal carcinogenesis. Most of the time, bacterial toxins are involved in pro-inflammatory processes and in activation of angiogenesis and cellular proliferation pathways. The identification of these bacteria leads to envisage the gut microbiota as potential screening tool for colorectal cancer. Recent studies showed a relation between the gut microbiota and the efficacy and toxicity of chemotherapies (oxaliplatin, irinotecan) and immunotherapies (including ipilimumab). Therapeutic approaches targeting the gut microbiota are now available (probiotics, fecal microbiota transplantation…). New therapeutic strategy combining both chemotherapy and/or immunotherapy with an adjuvant treatment targeting the gut microbiota can now be developed in order to improve treatment response and tolerance.

Quel pourrait être le futur de la prise en charge de la maladie rénale chronique en nutrition ?

The nutrition care of patients with chronic kidney disease (CKD) remains a central question which is permanently studied. The benefits of a dietary protein restriction are once again enlightened, either by reducing the urea found to be hyperglycemic, thus improving the peripheric insulin sensitivity, or by decreasing phosphorus and FGF23 hormone, whose reductions are respectively associated with nephroprotection and diminution of cardiovascular events. The numerous researches conducted on the gut microbiota also open promising avenues to better understand the role of this ecosystem in CKD. Finally, the interest in incremental haemodialysis is revived, results show it may be associated with less loss of proteins and preservation of residual kidney function. The development of a nutritional score, informative of survival prediction, also offers the possibility to ensure a better follow-up of patients.

[Irritable bowel syndrome: New pathophysiological hypotheses and practical issues]. / Le syndrome de l'intestin irritable : nouvelles pistes physiopathologiques et conséquences pratiques.

In 2015, besides the fact that it still fills the gastroenterologists' offices and impairs patient's quality of life, the irritable bowel syndrome has considerably evolved on several points. The pathophysiology is now organized around a consensual hypothesis called the "brain-gut axis", which gather all the influences of peripheral factors as gut microbiota or local serotonin secretion, on the central pain perception, contributing to visceral hypersensitivity and transit modifications. About the diagnosis, the key message is "avoid over-prescription" of additional tests, and reminds that a positive clinical diagnosis based on Rome III criteria is possible after the elimination of simple clinical warning signs. Finally, the food component, a neglected and historical claim of patients, finally finds a strong scientific rational, with a diet low in fermentable sugar and polyols, that gives positive and reproducible results.

Gut microbiota in Malawian infants in a nutritional supplementation trial.

OBJECTIVES: To examine whether two forms of lipid-based nutrient supplements (LNS) or a micronutrient-fortified corn-soya blend were associated with development of the gut microbiota in Malawian infants, to assess the microbiota profiles at the age of 6 and 18 months and to follow the changes during the 12-month period. METHODS: This was a substudy of a 4-arm randomised controlled trial conducted in rural Malawi. Infants at the age of 6 months were randomised to receive no supplement during the primary follow-up period (control), 54 g/day of micronutrient-fortified LNS with milk protein base (milk LNS), 54 g/day of micronutrient-fortified LNS with soya protein base (soya LNS), or 71 g/day of micronutrient-fortified corn-soya blend for 12 months. Stool samples were collected at baseline (6 months) and end of trial (18 months). The 16S rRNA gene was amplified and subjected to multiplex sequencing. RESULTS: A total of 213 infants had paired microbiota data at 6 and 18 months of age. The Dirichlet-multinomial test showed no significant difference in microbiota profile between the four intervention groups at either age (each P > 0.10). Bifidobacterium longum was most abundant at both ages. Lactobacillus ruminis, Shigella and Salmonella were present. The abundance of Prevotella and Faecalibacterium increased with age (each P < 0.001), while Bifidobacteriaceae and Enterobacteriaceae exhibited significant decrease (each P < 0.001). CONCLUSIONS: Nutritional supplementation by LNS or corn-soya blend for twelve months did not affect the gut microbiota profile in the rural Malawian context.

Antimicrobial use in swine production and its effect on the swine gut microbiota and antimicrobial resistance.

Antimicrobials have been used in swine production at subtherapeutic levels since the early 1950s to increase feed efficiency and promote growth. In North America, a number of antimicrobials are available for use in swine. However, the continuous administration of subtherapeutic, low concentrations of antimicrobials to pigs also provides selective pressure for antimicrobial-resistant bacteria and resistance determinants. For this reason, subtherapeutic antimicrobial use in livestock remains a source of controversy and concern. The swine gut microbiota demonstrates a number of changes in response to antimicrobial administration depending on the dosage, duration of treatment, age of the pigs, and gut location that is sampled. Both culture-independent and -dependent studies have also shown that the swine gut microbiota contains a large number of antimicrobial resistance determinants even in the absence of antimicrobial exposure. Heavy metals, such as zinc and copper, which are often added at relatively high doses to swine feed, may also play a role in maintaining antimicrobial resistance and in the stability of the swine gut microbiota. This review focuses on the use of antimicrobials in swine production, with an emphasis on the North American regulatory context, and their effect on the swine gut microbiota and on antimicrobial resistance determinants in the gut microbiota.