Short-Term Amoxicillin-Induced Perturbation of the Gut Microbiota Promotes Acute Intestinal Immune Regulation in Brown Norway Rats

Abstract

The intestinal gut microbiota is essential for maintaining host health. Concerns have been raised about the possible connection between antibiotic use, causing microbiota disturbances, and the increase in allergic and autoimmune diseases observed during the last decades. To elucidate the putative connection between antibiotic use and immune regulation, we have assessed the effects of the antibiotic amoxicillin on immune regulation, protein uptake, and bacterial community structure in a Brown Norway rat model. Daily intra-gastric administration of amoxicillin resulted in an immediate and dramatic shift in fecal microbiota, characterized by a reduction of within sample (α) diversity, reduced variation between animals (β diversity), increased relative abundance of Bacteroidetes and Gammaproteobacteria, with concurrent reduction of Firmicutes, compared to a water control group. In the small intestine, amoxicillin also affected microbiota composition significantly, but in a different way than observed in feces. The small intestine of control animals was vastly dominated by Lactobacillus, but this genus was much less abundant in the amoxicillin group. Instead, multiple different genera expanded after amoxicillin administration, with high variation between individual animals, thus the small intestinal α and β diversity were higher in the amoxicillin group compared to controls. After 1 week of daily amoxicillin administration, total fecal IgA level, relative abundance of small intestinal regulatory T cells and goblet cell numbers were higher in the amoxicillin group compared to controls. Several bacterial genera, including Escherichia/Shigella, Klebsiella (Gammaproteobacteria), and Bifidobacterium, for which the relative abundance was higher in the small intestine in the amoxicillin group than in controls, were positively correlated with the fraction of small intestinal regulatory T cells. Despite of epidemiologic studies showing an association between early life antibiotic consumption and later prevalence of inflammatory bowel diseases and food allergies, our findings surprisingly indicated that amoxicillin-induced perturbation of the gut microbiota promotes acute immune regulation. We speculate that the observed increase in relative abundance of small intestinal regulatory T cells is partly mediated by immunomodulatory lipopolysaccharides derived from outgrowth of Gammaproteobacteria.

Optimizing Secondary Electrospray Ionization High-Resolution Mass Spectrometry (SESI-HRMS) for the Analysis of Volatile Fatty Acids from Gut Microbiome

“…It has been reported that the impact of antibiotics on the gut microbiome can be attributed to its antimicrobial spectrum and the antimicrobial activity in the colon depending on concentrations [ 46 , 47 ]. Previous studies examined the effect of several types of antibiotics on the perturbation of gut microbiota, which may lead to an alteration in colonic mucosal homeostasis and microbial metabolites [ 18 , 27 , 48 , 49 ]. Høverstad et al reported that considerably changed SCFA profiles were observed according to the administration of ampicillin (500 mg four times daily) in the human clinical trial [ 46 ].…”

“…The administration of antibiotics has been widely applied in the treatment and prevention of infectious diseases [ 26 ]. However, fewer studies have been conducted to evaluate the effect of antibiotics on the VFA profiles of the gut microbiota [ 26 , 27 ].…”

Short- and long-term effects of amoxicillin/clavulanic acid or doxycycline on the gastrointestinal microbiome of growing cats

“…Contradictory findings exist in the literature with humans, laboratory animals and in vitro studies reporting high interindividual effects [68], no effects [69,70], only shortterm effects [62,65], or both short-and long-term effects on microbial composition [60,71,72] after administration of amoxicillin with or without clavulanic acid. In a study in rats, a 7-day course of amoxicillin during the weaning period caused transient alterations in microbial composition that resolved by 20 days after its discontinuation [61].…”

“…Increased abundance of different species were observed by the end of treatment. Antibiotics, including doxycycline and amoxicillin most commonly either decrease [58][59][60][61][62], or do not have any effect on species richness [63]. Only few studies have reported an increase in species richness indices [64,65].…”

Intestinal Microbiota—A Promising Target for Antiviral Therapy?

“…Studies have shown that the intestinal microbiota plays an important role in modulating the immune system against viruses (12)(13)(14)(15). The regulatory effects of the intestinal microbiota on viral infection are closely intertwined with local and systemic immune responses and contribute to both congenital and adaptive immune responses (16,17).…”