PMID- 34393993 OWN - NLM STAT- MEDLINE DCOM- 20211221 LR - 20211221 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 12 DP - 2021 TI - Impact of Sodium Butyrate Treatment in LPS-Stimulated Peripheral Blood Mononuclear Cells of Poorly Controlled Type 2 DM. PG - 652942 LID - 10.3389/fendo.2021.652942 [doi] LID - 652942 AB - Type 2 diabetes mellitus (T2DM) is associated with chronic low-grade inflammation, which is marked by the dysregulation of innate and adaptive immune responses. Therefore, reducing inflammation, possibly through an immunoregulatory agent, may play a role in T2DM treatment. Butyrate is the most potent short-chain fatty acid (SCFA), and it exerts anti-inflammatory properties by inhibiting histone deacetylase activity. As an immunoregulatory agent, sodium butyrate can inhibit nuclear factor kB (NF-kB) activation and reduce the production of pro-inflammatory cytokines in immune cells. The aim of the study was to measure the level of plasma butyrate in poorly controlled T2DM and normoglycemic participants and to compare the response of peripheral blood mononuclear cells (PBMCs) to sodium butyrate treatment between the groups by measuring production of the following cytokines: tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, interferon (IFN)-gamma, IL-13, and IL-10. The in vitro study examined the PBMCs of 15 participants with poorly controlled T2DM and 15 normoglycemic participants. PBMCs were cultured with the following stimulations for two days at a temperature of 37 degrees C and 5% CO(2): 100 ng/mL lipopolysaccharide (LPS), 1 mM sodium butyrate, or a combination of 100 ng/mL LPS and 1 mM sodium butyrate. Plasma butyrate was measured using gas chromatography-mass spectrometry, and cytokines from culture supernatant were analyzed using magnetic beads multiplex assay. Plasma butyrate levels in participants with poorly controlled T2DM did not significantly differ from those in normoglycemic participants (p = 0.105). Compared to treatment with an LPS-stimulated PBMC culture, treatment with 1 mM sodium butyrate reduced the levels of TNF-alpha (p < 0.039) and IFN-gamma (p < 0.038) in normoglycemic participants. The same general trend was seen in PBMC from participants with poorly controlled T2DM, but higher variability appeared to preclude statistical significance. These data suggest that butyrate may modulate inflammatory cytokine production in human PBMCs, but more research is needed to determine if butyrate is anti-inflammatory in poorly controlled T2DM. CI - Copyright (c) 2021 Wibowo, Harbuwono, Tahapary, Kartika, Pradipta and Larasati. FAU - Wibowo, Heri AU - Wibowo H AD - Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. FAU - Harbuwono, Dante S AU - Harbuwono DS AD - Division of Metabolic Endocrinology and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. FAU - Tahapary, Dicky L AU - Tahapary DL AD - Division of Metabolic Endocrinology and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. FAU - Kartika, Rona AU - Kartika R AD - Division of Metabolic Endocrinology and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. FAU - Pradipta, Saraswati AU - Pradipta S AD - Integrated Laboratory, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. FAU - Larasati, Rahma A AU - Larasati RA AD - Department of Biomedicines, Faculty of Medicine, Universitas Muhammadiyah Jakarta, Jakarta, Indonesia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210729 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Cytokines) RN - 0 (IFNG protein, human) RN - 0 (IL10 protein, human) RN - 0 (IL13 protein, human) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-13) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B p50 Subunit) RN - 0 (NFKB1 protein, human) RN - 0 (TNF protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 107-92-6 (Butyric Acid) RN - 130068-27-8 (Interleukin-10) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adult MH - Anti-Inflammatory Agents/pharmacology MH - Butyric Acid/*pharmacology MH - Cytokines/metabolism MH - Diabetes Mellitus, Type 2/*blood/drug therapy/*immunology MH - Female MH - Humans MH - Inflammation MH - Interferon-gamma/metabolism MH - Interleukin-10/metabolism MH - Interleukin-13/metabolism MH - Interleukin-6/metabolism MH - Leukocytes, Mononuclear/*cytology/drug effects MH - Lipopolysaccharides/*chemistry/metabolism MH - Male MH - Middle Aged MH - NF-kappa B p50 Subunit/metabolism MH - Tumor Necrosis Factor-alpha/metabolism PMC - PMC8358792 OTO - NOTNLM OT - butyrate OT - inflammatory response OT - lipopolysaccharide (LPS) OT - peripheral blood mononuclear cells OT - poorly controlled type 2 diabetes mellitus COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/08/17 06:00 MHDA- 2021/12/22 06:00 PMCR- 2021/01/01 CRDT- 2021/08/16 05:48 PHST- 2021/01/13 00:00 [received] PHST- 2021/07/13 00:00 [accepted] PHST- 2021/08/16 05:48 [entrez] PHST- 2021/08/17 06:00 [pubmed] PHST- 2021/12/22 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2021.652942 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2021 Jul 29;12:652942. doi: 10.3389/fendo.2021.652942. eCollection 2021.