Sugarcane molasses enhances TGF-β secretion and FOXP3 gene expression by Bifidobacterium Animalis Subsp. Lactis stimulated PBMCs of Ulcerative Colitis patients

Shakurnia, Abdolhussein; Sheikhi, Abdolkarim; Mirzapour, Majeed; Baharifar, Vahid; Baharifar, Narges; Aghamohammadi, Nima; Sheikhi, Mehdi; Matinrad, Mehdi; Mousavinasab, Seyed Nouraddin; Sheikhi, Sepideh; Sheikhi, Razieh

doi:10.1016/j.ctim.2019.102210

Cited by 7 publications

(6 citation statements)

References 16 publications

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“…Regulatory T cells (Tregs) play a critical role in the regulation of self-tolerance and homeostasis (1)(2)(3). Tregs are classically defined as CD4+CD25+FoxP3+ cells, and they can in vitro and in vivo suppress CD4+ and CD8+ T cell-mediated immune responses through multiple mechanisms, including expression of CTLA-4, inhibitory cytokines secretion, metabolic disruption, granzymemediated cytotoxicity, and dendritic cell inhibition (4,5). Many studies have demonstrated that CD4(+)CD25(+)CD127 dim/− was a surrogate phenotype to identify human Treg cells (6,7).…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Sequencing Reveals the Transcriptome and TCR Characteristics of pTregs and in vitro Expanded iTregs

et al. 2021

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Regulatory T cells (Tregs) play a critical role in the maintenance of immune tolerance and tumor evasion. However, the relative low proportion of these cells in peripheral blood and tissues has hindered many studies. We sought to establish a rapamycin-based in vitro Treg expansion procedure in patients diagnosed with colorectal cancer and perform single-cell sequencing to explore the characteristics of Treg cells. CD25+ cells enriched from peripheral blood mononuclear cells (PBMC) of colorectal tumor patients were cultured in X-VIVO15 medium, supplemented with 5% human AB serum, L-glutamine, rapamycin, interleukin-2 (IL-2), and Dynabeads human Treg expander for 21 days to expand Tregs. Treg cells with satisfactory phenotype and function were successfully expanded from CD4+CD25+ cells in patients with colorectal cancer. The median expansion fold was 75 (range, 20–105-fold), and >90.0% of the harvest cells were CD4+CD25+CD127dim/− cells. The ratio of CD4+CD25+Foxp3+ cells exceeded 60%. Functional assays showed that iTregs significantly inhibited CD8+T cell proliferation in vitro. Single-cell sequencing showed that the transcriptome of pTreg (CD4+CD25+CD127dim/− cells isolated from PBMC of colorectal cancer patients) and iTreg (CD4+CD25+CD127dim/− cells expanded in vitro according to the above regimen) cells were interlaced. pTregs exhibited enhanced suppressive function, whereas iTregs exhibited increased proliferative capacity. TCR repertoire analysis indicated minimal overlap between pTregs and iTregs. Pseudo-time trajectory analysis of Tregs revealed that pTregs were a continuum composed of three main branches: activated/effector, resting and proliferative Tregs. In contrast, in vitro expanded iTregs were a mixture of proliferating and activated/effector cells. The expression of trafficking receptors was also different in pTregs and iTregs. Various chemokine receptors were upregulated in pTregs. Activated effector pTregs overexpressed the chemokine receptor CCR10, which was not expressed in iTregs. The chemokine CCL28 was overexpressed in colorectal cancer and associated with poor prognosis. CCR10 interacted with CCL28 to mediate the recruitment of Treg into tumors and accelerated tumor progression. Depletion of CCR10+Treg cells from tumor microenvironment (TME) could be used as an effective treatment strategy for colorectal cancer patients. Our data distinguished the transcriptomic characteristics of different subsets of Treg cells and revealed the context-dependent functions of different populations of Treg cells, which was crucial to the development of alternative therapeutic strategies for Treg cells in autoimmune disease and cancer.

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Section: Introductionmentioning

confidence: 99%

Single-Cell Sequencing Reveals the Transcriptome and TCR Characteristics of pTregs and in vitro Expanded iTregs

et al. 2021

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“…Regarding the efficacy of B. lactis on UC, mice with DSS- or TNBS-induced colitis treated with B. lactis strains A6, BB12, and 5,764 showed significant improvements in intestinal barrier function and immunomodulation ( Chae et al, 2018 ; Hrdý et al, 2020 ; Wang et al, 2022 ). Furthermore, B. lactis exerts its anti-inflammatory properties through the activation of peripheral blood mononuclear cells and increasing forkhead box P3 (FOXP3) gene expression to increase TGF-β levels ( Shakurnia et al, 2019 ). Notably, B. lactis BL-99 not only reduced intestinal inflammation in UC but also alleviated colitis-related lung injury by altering SCFA production and inflammatory cell ratios ( Nan et al, 2023 ).…”

Section: Therapeutic Effects Of Probiotics On Ucmentioning

confidence: 99%

Probiotics for the treatment of ulcerative colitis: a review of experimental research from 2018 to 2022

et al. 2023

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Ulcerative colitis (UC) has become a worldwide public health problem, and the prevalence of the disease among children has been increasing. The pathogenesis of UC has not been elucidated, but dysbiosis of the gut microbiota is considered the main cause of chronic intestinal inflammation. This review focuses on the therapeutic effects of probiotics on UC and the potential mechanisms involved. In animal studies, probiotics have been shown to alleviate symptoms of UC, including weight loss, diarrhea, blood in the stool, and a shortened colon length, while also restoring intestinal microecological homeostasis, improving gut barrier function, modulating the intestinal immune response, and attenuating intestinal inflammation, thereby providing theoretical support for the development of probiotic-based microbial products as an adjunctive therapy for UC. However, the efficacy of probiotics is influenced by factors such as the bacterial strain, dose, and form. Hence, the mechanisms of action need to be investigated further. Relevant clinical trials are currently lacking, so the extension of animal experimental findings to clinical application requires a longer period of consideration for validation.

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“…Despite the loss of most sucrose, molasses extract is rich in B vitamins and minerals, including iron, calcium, magnesium, potassium, manganese, and various other nutrients that can be needed due to the urgent need of patients with IBDs such as UC (10). Studies have shown that the use of molasses as a flavoring in food on the market not only increases sales but also reduces the harmful effects of artificial flavors (11).…”

Section: Introductionmentioning

confidence: 99%

“…There is extremely limited information on the effects of molasses on the immune system of patients with UC. In 2019, Shakurnia et al investigated how the immune system of UC patients responds to molasses in vitro (11).…”

Section: Introductionmentioning

confidence: 99%

In Vitro Immunomodulatory Effects of Sugar-Free Sugarcane Molasses and Bifidobacterium animalis subsp. lactis on IFN-γ and TGF-β Secretion in Ulcerative Colitis Patients

Khalaf Shamsabadi,

Mirzaee,

Baharifar

et al. 2024

J Adv Immunopharmacol

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Background: Ulcerative colitis (UC) is an inflammatory bowel disease that leads to gastrointestinal ulcers. An overactive immune response against the intestinal microbiota has been suggested as one of the pathogenic factors. Some evidence indicates the immunomodulatory effects of Bifidobacterium lactis. sugarcane molasses, rich in vitamins and nutrients, can be used to compensate for the related nutrient deficiencies. Objectives: This study aims to evaluate the effects of sugar-free sugarcane (SFS)-molasses on the immune system of UC patients. Methods: Bifidobacterium lactis was cultivated in MRS broth and killed by UV de-sugarization of sugarcane molasses. It was prepared using the Steffen method. Peripheral blood mononuclear cells (PBMCs) of 12 UC patients were separated by Ficoll-Hypaque centrifugation. Peripheral blood mononuclear cells, SFS-molasses, and B. lactis were co-cultured. After 18h, the expression level of the FOXP3 gene was assessed by RT-qPCR (real-time PCR). The interferon gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured in the supernatant of PBMCs by ELISA. Results: Transforming growth factor beta in the SFS-molasses group was significantly increased compared to the controls (P = 0.032). The TGF-β in SFS-molasses + bacteria and the bacteria-alone groups increased compared to the control group (P = 0.039 and P = 0.049, respectively). The level of IFN-γ in the SFS-molasses group was significantly decreased compared to the controls (P = 0.004). Interferon gamma increased in the SFS-molasses + B. lactis group compared to the controls, but this was not significant. Expression of FOXP3 wasn’t affected after SFS-molasses treatment. Conclusions: These data showed that SFS molasses increases the levels of anti-inflammatory cytokine TGF-β and decreases the pro-inflammatory cytokine IFN-γ levels. These results may encourage researchers to continue studying the possible application of molasses as a nutritious food for patients with UC.

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Sugarcane molasses enhances TGF-β secretion and FOXP3 gene expression by Bifidobacterium Animalis Subsp. Lactis stimulated PBMCs of Ulcerative Colitis patients

Cited by 7 publications

References 16 publications

Single-Cell Sequencing Reveals the Transcriptome and TCR Characteristics of pTregs and in vitro Expanded iTregs

Single-Cell Sequencing Reveals the Transcriptome and TCR Characteristics of pTregs and in vitro Expanded iTregs

Probiotics for the treatment of ulcerative colitis: a review of experimental research from 2018 to 2022

In Vitro Immunomodulatory Effects of Sugar-Free Sugarcane Molasses and Bifidobacterium animalis subsp. lactis on IFN-γ and TGF-β Secretion in Ulcerative Colitis Patients

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