Table 2.
Impact of bacteria on Treg phenotype.
| Bacteria | Model | Impact on Tregs | Mechanism of Treg induction | Effect on immune system/ disease | References |
|---|---|---|---|---|---|
| Helicobacter pylori (likely mediated by CagA+ strains) | ↑ Splenic Tregs | DC-derived TGF-β | Presence in microbiota associated with decreased asthma, allergic disease, Inflammatory bowel disease | (114–118) | |
| ↑ FoxP3+ Treg induction in vitro | Bone marrow-derived DC secretion of IL-10 via TLR2 | ↑ gastritis and inflammation during H. pylori infection in Tlr2−/− mice | |||
| ↑ CD25+ T regulatory cell | Breg secretion of IL-10 via TLR2 activation | ↓ Gastric pathology in vivo | |||
| ↑ Pulmonary Tregs | DCs | ↓ airway inflammation in neonatal and adult mice | |||
| ↓ Mesenteric lymph node Tregs in Il−18−/− mice | Induction of IL-18 producing DCs | Transfer of CD25+ cells from Il18−/− or Il18r−/− mice lacked suppressive activity during airway allergic disease model | |||
| 7 strain mix: Lactobacillus acidophilus CBT LA1, Lactobacillus rhamnosus CBT LR5, Lactobacillus plantarum CBT LP3, Bifidobacterium bifidum CBT BF3, Bifidobacterium breve CBT BR3, Lactococcus lactis CBT SL6, Streptococcus thermophilus CBT ST3 |
SPF | ↑ CD25−FoxP3+ Tregs in MLNs, Foxp3 mRNA in skin | ↓ serum IgE, Th2 cytokines, dermatitis symptoms | (119) | |
| 5 strain mix (IRT5): Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium bifidium, Streptococcus thermophilus |
SPF | ↑ CD4+Foxp3+ Tregs in MLNs of healthy mice | Tolerogenic CD103c− CD11c+ DCs expressing IL-10, TGF-β, Cox-2, Indoleamine-pyrrole 2,3-dioxygenase | ↓ disease scores in Inflammatory bowel disease, atopic dermatitis, rheumatoid arthritis models, ↓ Th1, Th2, Th17 responses in T and B cells in vitro | (120) |
| Lactobacillus paracasei KBL382 | SPF | ↑ CD25+ Foxp3 Tregs in MLNs | Altered cecal microbiota profile, ↑ SCFAs and lactate, succinate, and fumarate | ↓ serum IgE, atopic dermatitis symptoms | (121) |
| Bacteroides thetaiotaomicron VPI 5482 and 29148 | SPF | ↑ CD4+Foxp3+ cells, CD4+ICOS+ T cells, CD4+ICOS+ Foxp3+ regulatory T cells, and IL-10-expressing CD4+Foxp3+ cells in spleen, MLN, and cervical lymph nodes | Possibly ↑ SCFA | ↓ OVA-specific IgE airway inflammation | (122, 123) |
| RORγt+ Treg homeostasis in the gut | Bile acid | Protection from colitis | |||
| 8 defined species of Altered Schaedler Flora | GF | ↑ Helios− Treg, activated CD103+ Treg, de novo generation of colonic Tregs of C57BL/6, BALB/c, Swiss, Webster, NMRI mice | TLR signalling through MyD88 and Ticam-1, independent of IL-10R signalling | Select monocolonisation unable to recapitulate effects of full Altered Schaedler Flora | (124) |
| Akkermansia muciniphila BAA-835, 139 | SPF | ↑ FoxP3+ Tregs in MLNs ↑MOG-specific FoxP3+ Tregs, total splenic Tregs, FoxP3+ Tregs in visceral adipose tissue |
↑ cecal SCFA concentration ↑TGF-β and ↓IL-6, IL-1β from MLN DCs ↑ ileal goblet cells which likely encourages tolerogenic DCs, ↓ IL-6, IL-1β in visceral adipose tissue | Normalised gut microbiota, ↑ recovery from DSS-colitis ↓ disease score in MS model improved metabolic profile in HFD-induced obesity |
(125, 126) |
| Bifidobacterium infantis 35624 | SPF | ↑ CD25+ Tregs in Peyer's Patch, CD25+ FoxP3+ splenic Tregs | Possibly ↓CD80 expression by DCs in Peyer's Patches and spleen ↑ | ↓ NF-κB activity, protection from S. typhimurium | (127, 128) |
| Human | ↑ FoxP3+ expression in peripheral blood CD4+ cells after oral feeding human volunteers for 8 weeks | IL-10 secretion, RALDH2, Indoleamine-pyrrole 2,3-dioxygenase expression in DC subsets in vitro via PRR activation | |||
| Bifidobacterium longum AH 1206 | GF, SPF | ↑ FoxP3+ Tregs in Peyer's Patch and spleen of infant, adult and GF models | Possibly altered genes of retinoic acid metabolism in Peyer's Patches | ↓ serum OVA-IgE, airway inflammation | (129) |
| Bacteroides fragilis NCTC934 | SPF | ↑ RORγt+ colonic Tregs | Bile acid metabolism | Bile acid supplementation protected from colitis |
(130–132) |
| Bacteroides fragilis 9343 | GF | ↑ IL-10+FoxP3+ colonic Tregs; enhanced CD4+ conversion to FoxP3+ in vitro | PSA induces tolerogenic DCs via TLR2 | PSA protects from colitis; protects from MS model | |
| Lactobacillus fermentum KBL374, KBL375 | SPF | ↑CD25+Foxp3+Tregs in MLNs | ↑ IL-10 colonic expression, Akkermansia expansion, altered cytokine expression | Protection from DSS colitis, normalised microbiota composition | (133–135) |
| ↑ CD25+Foxp3+ Tregs in MLN, Foxp3+ expression in skin | ↑ IL-10 in skin, SCFA concentration in cecum | ↓ serum IgE, atopic dermatitis, altered cecal microbiota |