Intestinal luminal putrescine is produced by collective biosynthetic pathways of the commensal microbiome

Nakamura, Atsuo; Ooga, Takushi; Matsumoto, Mitsuharu

doi:10.1080/19490976.2018.1494466

Cited by 59 publications

(41 citation statements)

References 52 publications

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“…Gut microbiota synthesize polyamines from arginine and its derivatives as well as lysine, cadaverine, putrescine, and spermidine [ 1 , 93 ]. Microbial production of polyamines abrogates the detrimental impact of aging on intestinal epithelia [ 94 , 95 ] and may serve protective roles against endothelial dysfunction [ 96 ] and neoplastic processes [ 97 ].…”

Section: Discussionmentioning

confidence: 99%

Dietary resistant starch preserved through mild extrusion of grain alters fecal microbiome metabolism of dietary macronutrients while increasing immunoglobulin A in the cat

Jackson¹,

Waldy²,

Jewell³

2020

PLoS ONE

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Dietary digestion-resistant starch (RS) provides health benefits to the host via gut microbiome-mediated metabolism. The degree to which cats manifest beneficial changes in response to RS intake was examined. Healthy cats (N = 36) were fed identically formulated foods processed under high (n = 17) or low (n = 19) shear extrusion conditions (low and high RS levels [LRS and HRS], respectively). Fecal samples collected after 3 and 6 weeks' feeding were assayed for stool firmness score, short-chain fatty acids, ammonia, and changes to the global metabolome and microbiome; fecal immunoglobulin A (IgA) was analyzed at week 6. Few differences were seen in proximate analyses of the foods; stool firmness scores did not differ. In cats consuming HRS food, concentrations of fecal butyrate and the straight chain:branched chain fatty acid ratio were significantly greater in feces at both weeks 3 and 6, while fecal ammonia was reduced at week 6 relative to feces from LRS-fed cats. Fecal IgA concentrations were significantly higher at week 6 with HRS food. RS consumption altered 47% of the fecal metabolome; RS-derived sugars and metabolites associated with greater gut health, including indoles and polyamines, increased in the cats consuming HRS food relative to those fed the LS food, while endocannabinoid N-acylethanolamines decreased. Consumption of HRS food increased concentrations of the ketone body 3-hydroxybutyrate in feces and elevated concentrations of reduced members of NADH-coupled redox congeners and NADH precursors. At the microbiome genus-level, 21% of operational taxonomic units were significantly different between food types; many involved taxa with known saccharolytic or proteolytic proclivities. Microbiome taxa richness and Shannon and Simpson alpha diversity were significantly higher in the HRS group at both weeks. These data show that feline consumption of grain-derived RS produces potentially beneficial shifts in microbiota-mediated metabolism and increases IgA production.

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Section: Discussionmentioning

confidence: 99%

Dietary resistant starch preserved through mild extrusion of grain alters fecal microbiome metabolism of dietary macronutrients while increasing immunoglobulin A in the cat

Jackson¹,

Waldy²,

Jewell³

2020

PLoS ONE

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“…First, polyamines may enhance virus binding to cells due to their polycationic nature, which mediates electrostatic interactions between the viral particles and the cell surface. This has significant physiological relevance for enteroviruses, as polyamines are abundant in the gut, through the combined effort of intestinal cells and the microbiota (40). Additionally, polyamines are abundant in seminal fluids (41), which may affect sexually transmitted viruses.…”

Section: Discussionmentioning

confidence: 99%

Polyamine Depletion Abrogates Enterovirus Cellular Attachment

Kicmal

Tate

Dial

et al. 2019

J Virol

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Polyamines are small polycationic molecules with flexible carbon chains that are found in all eukaryotic cells. Polyamines are involved in the regulation of many host processes and have been shown to be implicated in viral replication. Depletion of polyamine pools in cells treated with FDA-approved drugs restricts replication of diverse RNA viruses. Viruses can exploit host polyamines to facilitate nucleic acid packaging, transcription, and translation, but other mechanisms remain largely unknown. Picornaviruses, including Coxsackievirus B3 (CVB3), are sensitive to the depletion of polyamines and remain a significant public health threat. We employed CVB3 as a model system to investigate a potential proviral role for polyamines using a forward screen. Passaging CVB3 in polyamine-depleted cells generated a mutation in capsid protein VP3 at residue 234. We show that this mutation confers resistance to polyamine depletion. Through attachment assays, we demonstrate that polyamine depletion limits CVB3 attachment to susceptible cells, which is rescued by incubating virus with polyamines. Furthermore, the capsid mutant rescues this inhibition in polyamine-depleted cells. More divergent viruses also exhibited reduced attachment to polyamine-depleted cells, suggesting that polyamines may facilitate attachment of diverse RNA viruses. These studies inform additional mechanisms of action for polyamine-depleting pharmaceuticals, with implications for potential antiviral therapies. IMPORTANCE Enteroviruses are significant human pathogens that can cause severe disease. These viruses rely on polyamines, small positively charged molecules, for robust replication, and polyamine depletion limits infection in vitro and in vivo. The mechanisms by which polyamines enhance enteroviral replication are unknown. Here, we describe how Coxsackievirus B3 (CVB3) utilizes polyamines to attach to susceptible cells and initiate infection. Using a forward genetic screen, we identified a mutation in a receptor-binding amino acid that promotes infection of polyamine-depleted cells. These data suggest that pharmacologically inhibiting polyamine biosynthesis may combat virus infection by preventing virus attachment to susceptible cells.

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“…Different bacterial species, up to 1,000, constitute the intestinal microbiota. This community of microorganisms (bacteria, archaea, fungi, protozoa, viruses) is responsible for the metabolism of non- digested food components and it can supply to the host nutrients such as amino acids and vitamins and other biologically active substances (20). In general, this microbial consortium is subject to fluctuations due to different factors such as environment, diet, disease states and many others (21).…”

Section: Polyamines and Gut Microbiotamentioning

confidence: 99%