Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility

Ge, Xiaolong; Ding, Chao; Zhao, Wei; Xu, Lizhi; Tian, Hongliang; Gong, Jianfeng; Zhu, Min–Sheng; Li, Jieshou

doi:10.1186/s12967-016-1105-4

Cited by 193 publications

(156 citation statements)

References 37 publications

Supporting

Mentioning

135

Contrasting

Order By: Relevance

“…However, the antibiotic treatment affected only the caecum diameter and length, not those of the gastric and ileal lumen ( Table 2). These findings are in agreement with other reports showing the occurrence of macroscopic changes in the intestine of germ-free or antibiotic-treated mice (Reikvam et al, 2011;Grasa et al, 2015;Ge et al, 2017).…”

Section: Resultssupporting

confidence: 94%

Antibiotic‐induced dysbiosis of the microbiota impairs gut neuromuscular function in juvenile mice

Caputi

Marsilio

Filpa

et al. 2017

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSEGut microbiota is essential for the development of the gastrointestinal system, including the enteric nervous system (ENS). Perturbations of gut microbiota in early life have the potential to alter neurodevelopment leading to functional bowel disorders later in life. We examined the hypothesis that gut dysbiosis impairs the structural and functional integrity of the ENS, leading to gut dysmotility in juvenile mice. EXPERIMENTAL APPROACHTo induce gut dysbiosis, broad-spectrum antibiotics were administered by gavage to juvenile (3weeks old) male C57Bl/6 mice for 14 days. Bile acid composition in the intestinal lumen was analysed by liquid chromatography-mass spectrometry. Changes in intestinal motility were evaluated by stool frequency, transit of a fluorescent-labelled marker and isometric muscle responses of ileal full-thickness preparations to receptor and non-receptor-mediated stimuli. Alterations in ENS integrity were assessed by immunohistochemistry and Western blot analysis. KEY RESULTSAntibiotic treatment altered gastrointestinal transit, luminal bile acid metabolism and bowel architecture. Gut dysbiosis resulted in distorted glial network, loss of myenteric plexus neurons, altered cholinergic, tachykininergic and nitrergic neurotransmission associated with reduced number of nNOS neurons and different ileal distribution of the toll-like receptor TLR2. Functional defects were partly reversed by activation of TLR2 signalling. CONCLUSIONS AND IMPLICATIONSGut dysbiosis caused complex morpho-functional neuromuscular rearrangements, characterized by structural defects of the ENS and increased tachykininergic neurotransmission. Altogether, our findings support the beneficial role of enteric microbiota for ENS homeostasis instrumental in ensuring proper gut neuromuscular function during critical stages of development. Abbreviations

show abstract

Section: Resultssupporting

confidence: 94%

Antibiotic‐induced dysbiosis of the microbiota impairs gut neuromuscular function in juvenile mice

Caputi

Marsilio

Filpa

et al. 2017

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…It is usually a life-threatening condition during severe burn wound and lung infection, but humans carry P. aeruginosa usually asymptomatically in their intestines (Stoodley and Thom 1970). One reason for P. aeruginosa being benign in the human gut should be through the action of intestinal microbiota, which are part of the host defense to intestinal infection (Kamada et al 2013, Schubert et al 2015, Ge et al 2017. Previous studies describe the use of antibiotic cocktails that favor P. aeruginosa intestinal colonization by compromising resistance by the intestinal microbiota (Hentges et al 1985).…”

Section: Discussionmentioning

confidence: 99%

DefiningEscherichia colias a health-promoting microbe against intestinalPseudomonas aeruginosa

Christofi

Panayidou

Dieronitou

et al. 2019

Preprint

View full text Add to dashboard Cite

Gut microbiota acts as a barrier against intestinal pathogens, but species-specific protection of the host from infection remains relatively unexplored. Taking a Koch's postulates approach in reverse to define health-promoting microbes we find that Escherichia coli naturally colonizes the gut of healthy mice, but it is depleted from the gut of antibiotic-treated mice, which become susceptible to intestinal colonization by Pseudomonas aeruginosa and concomitant mortality. Reintroduction of fecal bacteria and E. coli establishes a high titer of E. coli in the host intestine and increases defence against P. aeruginosa colonization and mortality. Moreover, diet is relevant in this process because high sugars or dietary fat favours E. coli fermentation to lactic acid and P. aeruginosa growth inhibition. To the contrary, low sugars allow P. aeruginosa to produce the oxidative agent pyocyanin that inhibits E. coli growth. Our results provide an explanation as to why P. aeruginosa doesn't commonly infect the human gut, despite being a formidable microbe in lung and wound infections. Author SummaryHere we interrogate the conundrum as to why Pseudomonas aeruginosa is not a clinical problem in the intestine as opposed to other tissues. P. aeruginosa interacts with Neisseria, Streptococcus, Staphylococcus and Actinomyces species found in the human lung. These are predominantly gram-positive bacteria that induce P. aeruginosa virulence. Moreover, peptidoglycan, which is abundant in gram-positive bacteria, can directly trigger the virulence of P. aeriginosa. We reasoned that P. aeruginosa might be benign in the human gut due to the inhibitory action of benign gram-negative intestinal bacteria, such as Escherichia coli. Therefore, we dissected the antagonism between E. coli and P. aeruginosa and the effect of a conventional, a fat-, a carbohydrate-and a protein-based diet in intestinal dysbiosis. Our findings support the notion that an unbalanced diet or antibiotics induces gut dysbiosis by the elimination of commensal E. coli, in addition to lactic acid bacteria, imposing a gut environment conducive to P. aeruginosa infection. Moreover, commensal E. coli provides an explanation as to why P. aeruginosa doesn't commonly infect the human gut, despite being a formidable microbe in lung and wound infections.Antibiotics can also greatly affect microbiota diversity and promote dysbiosis. Early in life, antibiotic treatment can modulate the development of gut microbiota in children (Tanaka et al. 2009). In children and adults, opportunistic pathogens can take advantage of the antibiotic effect on commensal bacteria to infect the gut (Chang et al. 2008). One such pathogen is the gram-negative human opportunistic bacterium Pseudomonas aeruginosa, one of the most frequent species in hospital-acquired infections (Markou and Apidianakis 2013). While not a common clinical problem in the gut, P. aeruginosa colonizes the gastrointestinal tract of many hospitalized patients and to a lesser extent of healthy individuals (Ohara and Itoh 2003, Sh...

show abstract

“…For instance, GF mice exhibited approximately 3-fold lower levels of plasma serotonin compared to conventional SPF mice [136]. Furthermore, gut bacteria depletion by antibiotic treatment resulted in significantly lower 5-HT and 5-HT-positive staining cells in colon tissues [137]. In addition, microbiota from humanized and conventionally raised mice significantly increased the expression of serotonergic genes, including tryptophan hydroxylase 1 (rate-limiting enzyme for mucosal 5-HT synthesis) and chromogranin A (involved in neuroendocrine secretion) [138].…”

Section: Mechanisms Of Bottom-up Communicationmentioning

confidence: 96%

Role of Gut Microbiota in Neuroendocrine Regulation of Carbohydrate and Lipid Metabolism via the Microbiota-Gut-Brain-Liver Axis

2020

View full text Add to dashboard Cite

Gut microbiota play an important role in maintaining intestinal health and are involved in the metabolism of carbohydrates, lipids, and amino acids. Recent studies have shown that the central nervous system (CNS) and enteric nervous system (ENS) can interact with gut microbiota to regulate nutrient metabolism. The vagal nerve system communicates between the CNS and ENS to control gastrointestinal tract functions and feeding behavior. Vagal afferent neurons also express receptors for gut peptides that are secreted from enteroendocrine cells (EECs), such as cholecystokinin (CCK), ghrelin, leptin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), and 5-hydroxytryptamine (5-HT; serotonin). Gut microbiota can regulate levels of these gut peptides to influence the vagal afferent pathway and thus regulate intestinal metabolism via the microbiota-gut-brain axis. In addition, bile acids, short-chain fatty acids (SCFAs), trimethylamine-N-oxide (TMAO), and Immunoglobulin A (IgA) can also exert metabolic control through the microbiota-gut-liver axis. This review is mainly focused on the role of gut microbiota in neuroendocrine regulation of nutrient metabolism via the microbiota-gut-brain-liver axis.2 of 21 formate, acetate, propionate, and butyrate, which are related to maintaining intestinal epithelium and permeability [11]. Further, SCFAs regulate glucose and lipid metabolism as well as immune and inflammatory responses [12,13]. Hence, gut microbiota also plays an important role in immune systems, inflammation, and cancer prevention of the host [14,15]. The enteric nervous system (ENS) is reported to be involved in intestinal metabolic regulation, and enteric neurons and intestinal neurotransmitters play an important role in ENS regulation [16][17][18]. The gut contains full ENS reflex circuits, such as motor neurons, interneurons, and sensory neurons, and these neurons transfer information between the ENS and central nervous system (CNS). The vagal nerve pathway communicates between the CNS and ENS, which has remarkable impact on regulating gastrointestinal tract functions and feeding behavior [19,20]. Thus, the vagal nerve system is also involved in intestinal metabolic regulation through the gut-brain axis. Vagal afferent neurons express receptors for gut peptides, such as cholecystokinin (CCK), ghrelin, leptin, peptide tyrosine tyrosine (PYY), glucagon-like peptide-1 (GLP-1), 5-hydroxytryptamine (5-HT) and so on, which are secreted from enteroendocrine cells (EECs) [20][21][22]. When vagal afferent neurons sense these types of gut peptides, the corresponding gut information will transfer to the CNS and exert various reactions. At the same time, gut microbiota can regulate these gut peptides, such as CCK, ghrelin, leptin, PYY, GLP-1, 5-HT levels to influence vagal afferent pathway, and then regulated intestinal metabolic metabolism via the microbiota-gut-brain axis [23][24][25].The importance of the gut-brain axis in human health and disease has been known for a long period. However, it has only been re...

show abstract

Antibiotics-induced depletion of mice microbiota induces changes in host serotonin biosynthesis and intestinal motility

Cited by 193 publications

References 37 publications

Antibiotic‐induced dysbiosis of the microbiota impairs gut neuromuscular function in juvenile mice

Antibiotic‐induced dysbiosis of the microbiota impairs gut neuromuscular function in juvenile mice

DefiningEscherichia colias a health-promoting microbe against intestinalPseudomonas aeruginosa

Role of Gut Microbiota in Neuroendocrine Regulation of Carbohydrate and Lipid Metabolism via the Microbiota-Gut-Brain-Liver Axis

Contact Info

Product

Resources

About