Probiotic normalization of systemic inflammation in siblings of type 1 diabetes patients: an open-label pilot study

Abstract

The incidence of type 1 diabetes (T1D) has increased, coinciding with lifestyle changes that have likely altered the gut microbiota. Dysbiosis, gut barrier dysfunction, and elevated systemic inflammation consistent with microbial antigen exposure, have been associated with T1D susceptibility and progression. A 6-week, single-arm, open-label pilot trial was conducted to investigate whether daily multi-strain probiotic supplementation could reduce this familial inflammation in 25 unaffected siblings of T1D patients. Probiotic supplementation was well-tolerated as reflected by high participant adherence and no adverse events. Community alpha and beta diversity were not altered between the pre- and post-supplement stool samplings. However, LEfSe analyses identified post-supplement enrichment of the family Lachnospiraceae, producers of the anti-inflammatory short chain fatty acid butyrate. Systemic inflammation was measured by plasma-induced transcription and quantified with a gene ontology-based composite inflammatory index (I.I.com). Post-supplement I.I.com was significantly reduced and pathway analysis predicted inhibition of numerous inflammatory mediators and activation of IL10RA. Subjects with the greatest post-supplement reduction in I.I.com exhibited significantly lower CD4+ CD45RO+ (memory):CD4+ CD45RA+ (naïve) T-cell ratios after supplementation. Post-supplement IL-12p40, IL-13, IL-15, IL-18, CCL2, and CCL24 plasma levels were significantly reduced, while post-supplement butyrate levels trended 1.4-fold higher. Probiotic supplementation may modify T1D susceptibility and progression and warrants further study.

Does the Gut Microbiome Play a Role in Obesity in Type 1 Diabetes? Unanswered Questions and Review of the Literature

“…In humans, multi-strain probiotics have also been studied in the modulation of the immune system in 25 unaffected siblings of T1D patients who are considered at risk for T1D development. Results show that the probiotic was safe and well tolerated and that systemic inflammation was modestly reduced in response to the probiotic intake (Cabrera et al, 2022). In this study, markers of inflammation were significantly reduced after 6-weeks of probiotic supplementation (p = 0.017).…”

Association between red blood cell distribution width‐to‐albumin ratio and diabetic retinopathy

“…Normal tissue immune cells, such as regulatory T cells, macrophages, and eosinophils, exert anti‐inflammatory effects by synthesis of cytokines such as IL‐3, IL‐10, and IL‐4 thereby maintaining microenvironmental homeostasis 23,24 . When diabetes and its complications occur, the AGEs, lipid metabolism disorders and OS induce monocytes, macrophages as well as natural killer cells to infiltrate into the non‐inflammatory tissues such as fat and muscle, resulting in changes in the number and types of immune cells and the release of inflammatory factors which causes chronic inflammation 25 . The serum and vitreous and aqueous humor tissue of patients with diabetes contain a variety of inflammatory cytokines and chemokines.…”

“… 23 , 24 When diabetes and its complications occur, the AGEs, lipid metabolism disorders and OS induce monocytes, macrophages as well as natural killer cells to infiltrate into the non‐inflammatory tissues such as fat and muscle, resulting in changes in the number and types of immune cells and the release of inflammatory factors which causes chronic inflammation. 25 The serum and vitreous and aqueous humor tissue of patients with diabetes contain a variety of inflammatory cytokines and chemokines. A variety of eye tissue of patients with NPDR also contains inflammatory cytokines IL‐1 beta, IL‐6, IL‐8, TNF alpha, and mononuclear cells chemokine (monocyte chemotactic protein, MCP‐1) such as add.…”

Effects of Salinity on the Growth, Physiological Characteristics, and Intestinal Microbiota of the Echiura Worm (Urechis unicinctus)

“…Oscillospira probably produces the short-chain fatty acid butyrate and is suggested as an important candidate for the next generation of probiotics. Besides Oscillospira, Lachnospiraceae, and Clostridiales could also produce the anti-inflammatory short chain fatty acid butyrate (Atarashi et al, 2011;Cabrera et al, 2022). Butyrate has attracted much attention due to its beneficial effects on the host, such as trophic and antiinflammatory effects on epithelial cells (Inan et al, 2000) and has been proved to mediate host-microbial crosstalk in gut immune homeostasis (Hori et al, 2013;Furusawa et al, 2015).…”