Table 5.

Summary of major animal studies of prebiotic interventions, their mechanism of action and their outcomes related to T1D.

Name of Probiotic strains	Study type	Prebiotic type and dose	Duration of intervention	Mechanism of action	Outcomes	Reference	Year
Low antigen, hydrolyzed casein (HC)-based diet	LEW.1AR1-iddm ramodel	Fed daily	50 to 90 days	- Decreases in CD4+ Foxp3+ regulatory T (Treg) cells in pancreatic lymph nodes (PLN) - Decreases the expression of CD3+ T cells, CD163+ M2 macrophages and Foxp3+ Treg cells in the jejunum - decreases the Ifng/Il4 ratio, suggesting that the HC diet impacted M1/M2-associated cytokine balance - Corrects the gut immune cell deficits and increases the immunoregulatory capacity	- Prevention against T1D	(150)	2015
Dietary Resistant Starch	STZ-induced T1D Sprague-Dawley rats	550 g/kg diet	4 weeks	- Enhances GLP-1 and peptide YY secretion in vivo, which enhance β cell proliferation and insulin secretion improved the gut mucosal barrier - Protects the nephron	- Delayed the progression of diabetic nephropathy and maintained vitamin D balance in streptozotocin (STZ)-induced type 1 diabetic (T1D) rats develops normalized growth pattern in T1D	(151)	2016
Inulin-type fructans (ITFs), natural soluble dietary fibers with different degrees of fermentability from chicory root	NOD mice	Not mentioned	24weeks	- Increases CD25+Foxp3+CD4+ regulatory T cells, - Decreases IL17A+CD4+ Th17 cells, - Modulates cytokine production profile in the pancreas, spleen, and colon. - Increases the expression of barrier reinforcing tight junction proteins occludin and claudin-2, antimicrobial peptides β-defensin-1, and cathelicidin-related antimicrobial peptide - Enhances SCFAs production - Enhances Firmicutes/Bacteroidetes ratio to an antidiabetogenic balance and enriched modulatory Ruminococcaceae and Lactobacilli.	- Protects against autoimmune diabetes by modulating gut immunity, barrier function, and microbiota homeostasis. –> delays T1D development	(152)	2017
Wheat flour	NOD mice	Fed daily	72 days	- Lacks the epitopes linked with T1D - Reduces the levels of IFN-γ, a proinflammatory cytokine involved in the autoimmune pathogenesis of T1D - Increases the levels of IL-10, an anti-inflammatory cytokine potentially implicated in hindering T1D development	- Reduces the incidence of T1D.	(153)	2017
GABA therapy	STZ-induced C57BL/6 diabetic mice	Fed daily	11 weeks	- Increases Klotho levels in the serum, kidneys and pancreatic islets. - Stimulates the production and secretion of Klotho by human islet cells in vitro. - Stimulates the proliferation and insulin secretion by human islets - Klotho suppresses NF-κB activation - Increases insulin secretion	- Important implications for the treatment of T1D	(154)	2017
Caffeic acid-rich fraction from Prunella vulgaris L plant	Alloxan-induced diabetic mice	Fed daily	8 weeks	- Reduces blood glucose levels and improved in-vivo oxidative-stress - Inhibits the carbohydrate-hydrolyzing enzymes (alpha-amylase and alpha-glucosidase) - Reduces HbA1c levels - Increases serum-insulin levels	- Possess antidiabetogenic and antinociceptive properties could be a potential therapeutic agent to ameliorate T1D and related complications.	(155)	2018
Human milk oligosaccharides consisting of both long-chain, as well as short-chain structures	NOD mice	Fed daily	6 weeks	- Increases anti-inflammatory microbiota-generating metabolite [i.e., short chain fatty acids (SCFAs)] - Induces anti-diabetogenic cytokine profiles - Induces the development of tolerogenic dendritic cells (tDCs), priming of functional regulatory T cells, which support the protective effects - Increases butyrate production promoting mucin synthesis improving the intestinal barrier integrity	- Delays and suppresses T1D development in non-obese diabetic mice and reduces the development of severe pancreatic insulitis in later life - Vital in the protection of children at risk for T1D, supporting immune and gut microbiota development in early life.	(156)	2018