Dual role of microbiota-derived short-chain fatty acids on host and pathogen

Mirzaei, Rasoul; Dehkhodaie, Elahe; Bouzari, Behnaz; Rahimi, Mandana; Gholestani, Abolfazl; Hosseini‐Fard, Seyed Reza; Keyvani, Hossein; Teimoori, Ali; Karampoor, Sajad

doi:10.1016/j.biopha.2021.112352

Cited by 83 publications

(64 citation statements)

References 259 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nonetheless, recent molecular studies in combination with bacterial genetics and in vivo infection models have demonstrated the contributions of LCFAs in regulating the virulence potentials of bacterial pathogens in the gut. Finally, it should be noted that short chain fatty acids (SCFAs)nonesterified fatty acids with fewer than six carbonsare even more abundant within the gut and can also act as signaling molecules that modulate virulence through diverse mechanisms (Cummings et al, 1987;Lawhon et al, 2002;Gantois et al, 2006;Hung et al, 2013;Zhang et al, 2020;Hockenberry et al, 2021;Hobbs et al, 2021), recently reviewed here (Mirzaei et al, 2021).…”

Section: Long Chain Fatty Acidsmentioning

confidence: 99%

Long Chain Fatty Acids and Virulence Repression in Intestinal Bacterial Pathogens

Mitchell

Ellermann

2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

When bacterial pathogens enter the gut, they encounter a complex milieu of signaling molecules and metabolites produced by host and microbial cells or derived from external sources such as the diet. This metabolomic landscape varies throughout the gut, thus establishing a biogeographical gradient of signals that may be sensed by pathogens and resident bacteria alike. Enteric bacterial pathogens have evolved elaborate mechanisms to appropriately regulate their virulence programs, which involves sensing and responding to many of these gut metabolites to facilitate successful gut colonization. Long chain fatty acids (LCFAs) represent major constituents of the gut metabolome that can impact bacterial functions. LCFAs serve as important nutrient sources for all cellular organisms and can function as signaling molecules that regulate bacterial metabolism, physiology, and behaviors. Moreover, in several enteric pathogens, including Salmonella enterica, Listeria monocytogenes, Vibrio cholerae, and enterohemorrhagic Escherichia coli, LCFA sensing results in the transcriptional repression of virulence through two general mechanisms. First, some LCFAs function as allosteric inhibitors that decrease the DNA binding affinities of transcriptional activators of virulence genes. Second, some LCFAs also modulate the activation of histidine kinase receptors, which alters downstream intracellular signaling networks to repress virulence. This mini-review will summarize recent studies that have investigated the molecular mechanisms by which different LCFA derivatives modulate the virulence of enteric pathogens, while also highlighting important gaps in the field regarding the roles of LCFAs as determinants of infection and disease.

show abstract

Section: Long Chain Fatty Acidsmentioning

confidence: 99%

Long Chain Fatty Acids and Virulence Repression in Intestinal Bacterial Pathogens

Mitchell

Ellermann

2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Metabolites produced by a healthy gut microbiota, such as short-chain fatty acids (e.g., acetic, propionic, and butyric acids), play important roles in maintaining the intestinal barrier, ( 43 ) providing energy ( 44 ) and immune homeostasis ( 45 ). It is well-recognized that gut microbiota also participate in modulating the intestinal microenvironment and host metabolism, while the gut microecology is vulnerable to the effects of unhealthy diet ( 46 ) and antibiotic treatments ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Shifts in Fecal Metabolite Profiles Associated With Ramadan Fasting Among Chinese and Pakistani Individuals

Chen

Ikram

et al. 2022

Front. Nutr.

View full text Add to dashboard Cite

The human gut microbiota has been proposed to serve as a multifunctional organ in host metabolism, contributing effects to nutrient acquisition, immune response, and digestive health. Fasting during Ramadan may alter the composition of gut microbiota through changes in dietary behavior, which ultimately affects the contents of various metabolites in the gut. Here, we used liquid chromatography–mass spectrometry-based metabolomics to investigate the composition of fecal metabolites in Chinese and Pakistani individuals before and after Ramadan fasting. Principal component analysis showed distinct separation of metabolite profiles among ethnic groups as well as between pre- and post-fasting samples. After Ramadan fasting, the Chinese and Pakistani groups showed significant differences in their respective contents of various fecal metabolites. In particular, L-histidine, lycofawcine, and cordycepin concentrations were higher after Ramadan fasting in the Chinese group, while brucine was enriched in the Pakistani group. The KEGG analysis suggested that metabolites related to purine metabolism, 2-oxocarboxylic acid metabolism, and lysine degradation were significantly enriched in the total subject population pre-fasting vs. post-fasting comparisons. Several bacterial taxa were significantly correlated with specific metabolites unique to each ethnic group, suggesting that changes in fecal metabolite profiles related to Ramadan fasting may be influenced by associated shifts in gut microbiota. The fasting-related differences in fecal metabolite profile, together with these group-specific correlations between taxa and metabolites, support our previous findings that ethnic differences in dietary composition also drive variation in gut microbial composition and diversity. This landscape view of interconnected dietary behaviors, microbiota, and metabolites contributes to the future development of personalized, diet-based therapeutic strategies for gut-related disorders.

show abstract

“…Both the activity of thew immune system and the anti-inflammatory effects could be mediated by SCFAs in chronic diseases ( 32 , 33 ). Moreover, the gut microbiota can affect the excretion of UA by the production of SCFAs ( 26 – 28 ).…”

Section: Discussionmentioning

confidence: 99%

Altered Gut Microbiota in Children With Hyperuricemia

et al. 2022

View full text Add to dashboard Cite

BackgroundIn adults, gut dysbiosis may contribute to the pathogenesis of gout. However, the characteristics of gut microbiota in children with hyperuricemia (HUA) in the absence of clinical gout have not been explored.ObjectiveThis present study analyzed the gut microbiota in children with HUA as compared to controls (Con) and explored bacterial associations that may account for differences.MethodsA total of 80 children were enrolled in this study; they were divided into HUA and Con according to the level of serum uric acid (UA). The composition of gut microbiota was investigated by 16S rRNA high-throughput sequencing.ResultsPrincipal coordinate analysis revealed that gut microbiota of the HUA group was clustered together and separated partly from the Con group. There was no difference in alpha-diversity between the two groups. However, Spearman’s correlation analysis revealed that serum UA level positively correlated with genera Actinomyces, Morganella, and Streptococcus, and negatively associated with the producers of short-chain fatty acids (SCFAs), such as Alistipes, Faecalibacterium, and Oscillospira, and the sulfidogenic bacteria Bilophila. The members of the genera Alistipes and Bilophila in the Con group were significantly more prevalent than the HUA subjects. Compared to the Con cohort, metabolic pathway predictions found that the superpathways of purine nucleotide de novo biosynthesis were decreased in HUA subjects, whereas the superpathway of purine deoxyribonucleoside de gradation was increased.ConclusionThe composition of the gut microbiota in children with HUA differs from Con. Although causality cannot be established, modification in the microbiota that produces SCFA and sulfide may promote HUA.

show abstract

Dual role of microbiota-derived short-chain fatty acids on host and pathogen

Cited by 83 publications

References 259 publications

Long Chain Fatty Acids and Virulence Repression in Intestinal Bacterial Pathogens

Long Chain Fatty Acids and Virulence Repression in Intestinal Bacterial Pathogens

Shifts in Fecal Metabolite Profiles Associated With Ramadan Fasting Among Chinese and Pakistani Individuals

Altered Gut Microbiota in Children With Hyperuricemia

Contact Info

Product

Resources

About