Probiotic-Derived Ecto-5'-Nucleotidase Produces Anti-Inflammatory Adenosine Metabolites in Treg-Deficient Scurfy Mice

Liu, Yuying; Armbrister, Shabba A.; Okeugo, Beanna; Mills, Tingting; Daniel, Rhea C.; Oh, Jee-Hwan; Pijkeren, Jan-Peter van; Park, Evelyn S.; Saleh, Zeina M.; Lahiri, Sharmistha; Roos, Stefan; Rhoads, J. Marc

doi:10.1007/s12602-023-10089-z

Cited by 4 publications

(6 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In SF mice, the absence of this control mechanism could be reversed by probiotic-derived adenosine and the adenosine metabolite inosine. Adenosine and inosine act as agonists of the adenosine receptor A 2A to control inflammation [ 18 , 27 , 43 ]. DSM 17938 may influence other bacteria-associated metabolites, including amino acids and their derivatives such as glutamine, tryptophan/indoles, and polyamines.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Probiotic Limosilactobacillus reuteri DSM 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia and Chronic Hepatitis in Mice

Nessim Kostandy,

Suh,

Tian

et al. 2024

Nutrients

Self Cite

View full text Add to dashboard Cite

The probiotic Limosilactobacillus reuteri DSM 17938 produces anti-inflammatory effects in scurfy (SF) mice, a model characterized by immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (called IPEX syndrome in humans), caused by regulatory T cell (Treg) deficiency and is due to a Foxp3 gene mutation. Considering the pivotal role of lipids in autoimmune inflammatory processes, we investigated alterations in the relative abundance of lipid profiles in SF mice (± treatment with DSM 17938) compared to normal WT mice. We also examined the correlation between plasma lipids and gut microbiota and circulating inflammatory markers. We noted a significant upregulation of plasma lipids associated with autoimmune disease in SF mice, many of which were downregulated by DSM 17938. The upregulated lipids in SF mice demonstrated a significant correlation with gut bacteria known to be implicated in the pathogenesis of various autoimmune diseases. Chronic hepatitis in SF livers responded to DSM 17938 treatment with a reduction in hepatic inflammation. Altered gene expression associated with lipid metabolism and the positive correlation between lipids and inflammatory cytokines together suggest that autoimmunity leads to dyslipidemia with impaired fatty acid oxidation in SF mice. Probiotics are presumed to contribute to the reduction of lipids by reducing inflammatory pathways.

show abstract

Section: Discussionmentioning

confidence: 99%

“…b.w./day beginning on d10 had been established [ 24 , 39 , 42 ]. In Treg-deficient SF mice, daily intragastric administration of 10 7 cfu/day until d21 reduced the severity [ 18 , 25 , 43 ]. Mice were euthanized at age d22 to collect blood and cecal/colonic contents.…”

Section: Methodsmentioning

confidence: 99%

Probiotic Limosilactobacillus reuteri DSM 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia and Chronic Hepatitis in Mice

Nessim Kostandy,

Suh,

Tian

et al. 2024

Nutrients

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, the mechanism of Tregs induction may be associated with reprogrammed gut microbiota composition and SCFAs production by L. reuteri (Liu et al, 2019;Wen et al, 2021). However, the ability of L. reuteri to induce Tregs is generally strain-dependent, and certain L. reuteri strains have anti-inflammatory properties that are not always reliant on Tregs (Liu et al, 2021b;Liu et al, 2023a). Orally feeding L. reuteri can suppress Th1/Th2 responses in mesenteric lymph nodes in Treg-deficient mice via activation of adenosine A 2A receptors (Liu et al, 2023a).…”

Section: Regulation Of Immune Cell Differentiation and Functionmentioning

confidence: 99%

“…However, the ability of L. reuteri to induce Tregs is generally strain-dependent, and certain L. reuteri strains have anti-inflammatory properties that are not always reliant on Tregs (Liu et al, 2021b;Liu et al, 2023a). Orally feeding L. reuteri can suppress Th1/Th2 responses in mesenteric lymph nodes in Treg-deficient mice via activation of adenosine A 2A receptors (Liu et al, 2023a). This phenomenon may be explained by the specific property of L. reuteri to increase the level of plasma adenosine metabolites such as inosine (Liu et al, 2021b).…”

Section: Regulation Of Immune Cell Differentiation and Functionmentioning

confidence: 99%

Lactobacillus reuteri in digestive system diseases: focus on clinical trials and mechanisms

Peng,

Ma,

Luo

et al. 2023

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

ObjectivesDigestive system diseases have evolved into a growing global burden without sufficient therapeutic measures. Lactobacillus reuteri (L. reuteri) is considered as a new potential economical therapy for its probiotic effects in the gastrointestinal system. We have provided an overview of the researches supporting various L. reuteri strains’ application in treating common digestive system diseases, including infantile colic, diarrhea, constipation, functional abdominal pain, Helicobacter pylori infection, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases.MethodsThe summarized literature in this review was derived from databases including PubMed, Web of Science, and Google Scholar.ResultsThe therapeutic effects of L. reuteri in digestive system diseases may depend on various direct and indirect mechanisms, including metabolite production as well as modulation of the intestinal microbiome, preservation of the gut barrier function, and regulation of the host immune system. These actions are largely strain-specific and depend on the activation or inhibition of various certain signal pathways. It is well evidenced that L. reuteri can be effective both as a prophylactic measure and as a preferred therapy for infantile colic, and it can also be recommended as an adjuvant strategy to diarrhea, constipation, Helicobacter pylori infection in therapeutic settings. While preclinical studies have shown the probiotic potential of L. reuteri in the management of functional abdominal pain, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases, its application in these disease settings still needs further study.ConclusionThis review focuses on the probiotic effects of L. reuteri on gut homeostasis via certain signaling pathways, and emphasizes the importance of these probiotics as a prospective treatment against several digestive system diseases.

show abstract

“…Accordingly, (43) showed that new-born mice supplemented with L. reuteri had increased levels of adenosine in plasma after treatment. Additionally, Liu et al 2023 showed that DSM 17938 and BG-R46 can prolong the survival of scurfy mice by antiinflammatory adenosine signaling (44). Thus, strains of both L. reuteri and B. longum can be potent regulators of gastrointestinal functions and have been described to mediate multiple health-promoting effects.…”

Section: Introductionmentioning

confidence: 99%

Bifidobacterium longumsubsp. longumBG-L47 boosts growth and activity ofLimosilactobacillus reuteriDSM 17938 and its extracellular membrane vesicles

Lundberg,

Mishra,

Liu

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

The aim was to identify aBifidobacteriumstrain that improved the performance ofLimosilactobacillusreuteriDSM 17938. Initial tests showed thatBifidobacteriumlongumsubsp.longumstrains boosted the growth of DSM 17938 during in vivo-like conditions. Further characterization revealed that one of the strains, BG-L47, had better bile and acid tolerance compared to BG-L48, as well as mucus adhesion compared to both BG-L48 and the control strain BB536. BG-L47 also had the capacity to metabolize a broad range of carbohydrates and sugar alcohols. Mapping of glycoside hydrolase (GH) genes of BG-L47 and BB536 revealed many GHs associated with plant-fiber utilization. However, BG-L47 had a broader phenotypic fiber utilization capacity. In addition,B. longumsubsp.longumcells boosted the bioactivity of extracellular membrane vesicles (MV) produced byL. reuteriDSM 17938 during cocultivation. Secreted 5’ nucleotidase (5’NT), an enzyme that converts AMP into the signal molecule adenosine, was increased in MV boosted by BG-L47. The MV exerted an improved antagonistic effect on the pain receptor TRPV1 and increased the expression of the immune development markers IL-6 and IL-1ß in a PBMC model. Finally, the safety of BG-L47 was evaluated both by genome safety assessment and in a human safety study. Microbiota analysis showed that the treatment did not induce significant changes in the composition. In conclusion,B. longumsubsp.longumBG-L47 has favorable physiological properties, can boost the in vitro activity ofL. reuteriDSM 17938, and is safe for consumption, making it a candidate for further evaluation in probiotic studies.

show abstract

Probiotic-Derived Ecto-5'-Nucleotidase Produces Anti-Inflammatory Adenosine Metabolites in Treg-Deficient Scurfy Mice

Cited by 4 publications

References 66 publications

Probiotic Limosilactobacillus reuteri DSM 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia and Chronic Hepatitis in Mice

Probiotic Limosilactobacillus reuteri DSM 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia and Chronic Hepatitis in Mice

Lactobacillus reuteri in digestive system diseases: focus on clinical trials and mechanisms

Bifidobacterium longumsubsp. longumBG-L47 boosts growth and activity ofLimosilactobacillus reuteriDSM 17938 and its extracellular membrane vesicles

Contact Info

Product

Resources

About