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269 LA IMPRENTA EN FILIPINAS 370
Antibiotics are commonly used to control bacterial infection of humans and animals in hospitals and on farms. Administration of antibiotics can strongly affect the composition of the intestinal microbiota of both adult pigs (Chapter 3) and piglets (Chapter 4). In Chapter 3, when amoxicillin was administrated to the sows, it inhibited bacteria related to
L.acidophilus, L. delbrueckii, L. gasseri, L. plantarum, S. aureus, S. bovis, S. intermedius and S.suis. This result is in line with previous reports showing that amoxicillin commonly had an inhibiting effect on Lactobacillus, Streptococcus and Staphylococcus [59, 208-210].
Figure 1. Overview of the main findings described in this thesis. This thesis determined the impact of maternal
antibiotic treatment (Orange), early antibiotic administration (Red), and early microbial exposure to sows’ faeces (Purple) on piglets’ intestinal microbiota and mucosal tissue gene expression at early age, as well as resistant starch (RS, Green) on microbiota, short-chain fatty acid (SCFA) concentration and host gene expression in the large intestine of adult pigs. Antibiotic treatment of sows during the perinatal period (Orange pies) caused a decrease in relative abundance of bacteria related to Lactobacillus, Staphylococcus and Streptococcus of sows’ faeces, and led to increased relative abundance of Proteobacteria in piglets’ faeces, mainly driven by a stimulation of Escherichia coli and Pseudomonas during administration (Orange plate). Early antibiotic administration to piglets (Red pie) affected composition and diversity of gut microbiota and reduced the mucosal tissue expression of host genes associated with a large number of immune-related processes (Red plate). Exposure of caesarian derived newborn piglets to sows’ faeces (Purple pie) affected the piglet’s intestinal microbiota and enriched ileal mucosal gene sets linked to immune system development, whereas effects on jejunal microbiota and gene expression was less clear (Purple plate). RS (Green pie) modulated the microbiota composition, short chain fatty acid (SCFA) concentration and mucosal tissue gene expression in the large intestine of adult pigs (Green plate). The RS diet induced the stimulation of health associated butyrate-producing bacteria, whereas potentially pathogenic members were reduced in relative abundance. Caecal and colonic SCFA concentrations were significantly higher in RS-fed pigs, and caecal expression of genes encoding for monocarboxylate transporter 1 (SLC16A1) and glucagon (GCG) was induced by RS. Concentrations in carotid plasma of acetate, propionate, and butyrate were significantly higher following RS consumption. RS induced oxidative metabolic pathways, whereas many immune response pathways and cell division were suppressed.
However, in the study described here, such inhibiting effect was not observed in the intestinal microbiota of piglets. Moreover, microbial groups that were affected both in faeces of amoxicillin-treated sows and ileal content of their offspring, showed an opposite direction of change. For example, amoxicillin caused an increased relative abundance of bacteria related to Alistipes in treated sows’ faeces, whereas this population was decreased
in the ileal content of the offspring at the age of 14 days. These opposing findings may suggest that the maternal amoxicillin treatment may indirectly affect the gut microbiota of the offspring through disturbing the maternal microbiota. Since maternal microbiota can be transferred to the offspring (see Chapter 1), the impact will be manifested in the next generation. Another possible explanation is that amoxicillin-resistance genes or bacteria harbouring these have been selected and transferred from the mothers to their offspring. Therefore, these genes or bacteria that harbour them in the piglet gut showed increased relative abundance, whereas sensitive bacteria were reduced by the maternal amoxicillin. However, the present study is not conclusive on the main mechanism by which maternal amoxicillin affected the intestinal microbial of the offspring. Further analysis should be performed to characterize the milk microbiota as well as determine potential amoxicillin residues directly transferred from the mothers to their offspring.
Chapter 4 describes that when the antibiotic was directly administered to the piglets at an early age, it caused an increase of the microbial diversity as well as the relative abundance of Bifidobacterium. This finding differs from the conclusion of most previous human infant studies summarized in Chapter 1. One possible reason could be that all the previous infant studies determined the effect of antibiotics in faecal samples, whereas in the current piglet study we analyzed the microbiota in jejunal content. Therefore, our piglet study can not directly be compared to the previous human infant studies. On the other hand, the used antibiotics also differ. In our present study, piglets received an injection (subcutaneously in the neck) with 0.1 ml tulathromycin at day 4 after birth. Tulathromycin is a triamilide macrolide antibiotic found to be safe and effective against respiratory bacterial pathogens in cattle and swine. However, the effect of tulathromycin on the gut microbiota has not been studied in detail up to now. This thesis is the first report that tulathromycin impacts the gut microbiota of piglets. As shown in Chapter 1, most of the human infant studies evaluate β-Lactam antibiotics such as amoxicillin, cefalexin and ampicillin. Considering the various targets, doses, and durations of antibiotic treatment, it is not surprising that gut microbial communities respond to different antibiotics in different ways or even in opposite ways.
Microbial exposure at early age
Microbial exposure at early age is probably the most complicated factor to determine when studying the development of intestinal microbiota. Just like the individual variation of each person’s or animal’s gut microbiota, the microbial exposure at early age for each individual can also strongly vary, due to the fact that microbial exposure of infants and young animals seems to happen everywhere. Starting from birth, the neonates are exposed to either their mothers’ vaginal and faecal bacteria or a more complex indoor microbial environment which includes their mothers’ skin microbiota, mostly depending on the mode of delivery [31-33]. Later on, the infants and young animals may continue to be exposed to their
mother’s milk, skin and faecal microbiota during daily contact [37, 38, 191, 207, 376]. At the same time, infants and young animals are exposed to a broad range of indoor and outdoor microbial environments, such as hospital and day care for infants and farms for animals [46, 48-50]. It seems that the microbial exposure at early age is to some extent accidental, and earliest colonization events are determined by opportunistic colonization by bacteria to which an infant or a piglet is exposed in its environment [13]. Such opportunistic colonization can be one of the reasons that explain the individual variation of the intestinal microbiota.