Table 1.

Studies in non-human models of inflammation and their consequences for taste from 2016 to 2020

Reference	Study objective	Study Design	Model	Measures	Results	Conclusions
Ahart et al. (2020) [6••]	Determine whether HFD or obesity itself induced taste deficits	Mice on HFD or Chow with or without Captopril (CAP) in water for 6 weeks	C57BL/6 mice Diet Induced Obesity (DIO)	Sucrose licking, calcium imaging of taste cells, taste gene expression.	HFD but not Obesity reduced licking of sucrose. Diet independently inhibited TRC activity. No decrease of TBs in HFD. Decrease in PLCB2	Both diet itself and obesity independently impact taste.
Kaufman et al (2020) [7]	Taste stem cell associated markers were measure in obese and lean mice	Mice on control diets or HFD for 8 weeks.	C57BL/6J Male mice, circumvallate papillae gene expression	qRT-PCR, genes expressed in TBs isolated from CV of mice.	Reduction of expression in HFD-fed mice of markers of proliferation->Ki-67 and β-catenin, and markers of all taste cell types- PLCβ2, KCNQ1, NPTDase2, PKD2L1	Gene expression of proliferation markers significantly reduced in the TBs of obese mice.
Bernard et al. (2019) [8]	Explore fat detection in obese rodents	1) Mice on chronic HFD and 2) 4 week treatment with LPS through osmotic pump to recreate a chronic inflammation.	C57Bl/6 male mice age 8 weeks	Two bottle preference with oil solution, LPS detection, taste gene expression,	DIO mice had a decreased preference for oil. Plasma LPS increased in DIO mice. LPS alone did not change preference for oil. Proinflammatory genes increase in Circumvallate Papillate (CVP) of LPS mice with NFκB a central mediator	Orosensory perception of fat is affected by a fatty diet, but not by a non-diet LPS induced proinflammatory state
Bernard et al. (2019) [9••]	Determine whether prebiotic supplementation reverses DIO taste changes in mice	Mice on Chow or HFD alone and supplemented with 10% prebiotic for 12 weeks.	C57 Bl / 6 males. Age 7 weeks to start.	Two bottle taste preference, gustometer, blood draw, gut microbiota	DIO group reduced response to sucrose in two bottle and gustometer. Partially rescued by prebiotic (P). Proglucagon increase in DIO+Probiotic group	Though markers weren’t measured, the authors indicate anti-inflammatory effects of prebiotic might partially explain sweet taste rescue
Kaufman et al. (2018) [10••]	Investigate association of obesity with taste abundance in mice	Wild type C57, TNFαKO and Sel 1L adipocyte KO fed HFD or Chow. Acute injection of TNFα or vehicle into tongue.	8-week-old C57 Bl/6, B6.129S-Tnftm1Gkl/J, Sel 1L-/- ,all male	Taste bud and Taste Receptor Cell and taste progenitor cell counting, mRNA of stem cells and taste transduction markers.	Obese mice have elevated TNFα and concomitant taste bud loss. TNFα null mice and obese-resistant mice are protected. Taste progenitor (Ki67+) cells also reduced with bud loss.	Inflammation arising from obesity, associated with adipose tissue reduces the # of taste buds through a reduction in progenitor cells.
Djezriri et al. (2018) [11••]	Mediterranean diets high in polyunsaturated fats exert anti-obesity effects. Mechanism explored in mice.	Mice on control diets or HFD with poly unsaturated fat in water or vehicle.	C57BL/6J Female mice on Chow, HFD, or HFD + oleanolic acid (OLA) in water for 16 weeks.	Plasma LPS, Taste Preference, Cytokine mRNA, fatty acid composition of tissue, blood glucose tolerance test.	OLA decreases weight gain of HFD mice, rescues CD36 expression, improves Glucose response, and reduces plasma LPS. Reduces TNFα, IL-1β, and IL-6 vs HFD alone. Ca2+ flux to OLA was abolished in HFD but rescued with HFD + OLA mice in a through CD36 independent pathway.	Reduction in bodyweight, pro-inflammatory cytokines, glucose response, and restoration of taste acuity all through addition of OLA to diet.
Feng et al. (2018) [12••]	As TRCs have been found in the gut, group investigated whether α-Gustducin has a role in IBD, a gut inflammatory disorder	Induced colitis in either C57Bl/6 or their α-Gust null counterparts.	Animal model of IBD, using dextran sulfate sodium (DSS) to induce inflammation in α-gust-KO mice. M /F both used. 3% DSS in water for 7 days, then mice were euthanized.	Weight, cytokine measures in colon tissue, immunohistochemistry (IHC)	α-Gust null mice had more severe colitis than WT, lost more weight, had higher tissue injury score, more inflammatory cell infiltration in colons plus an increase in TNF and IFN-γ. Decrease in IL-5, IL-13, IL-10	α-Gust serves a critical role in protecting the colon from inflammation.
Sharma et al. (2017) [13••]	GPCRs in Asthma are targets for treatment. As new evidence implicates T2R bitter receptors, which are GPCRS, in inflammatory pathways, bitter taste receptor agonists were tested as asthma treatments.	Mice treated with T2R agonists chloroquine (CQ) or quinine (Q) and challenged with Ovalbumin (OVA) or House Dust Mites (HDM) Used human neutrophils to determine mechanism	Male FVB/N mice 8 weeks old; Injected with OVA Intraperitoneally then challenged with or without agonists. Female BALB/c mice 8 weeks old challenged with HDM. Two models; Prophylactic: pre-treated with agonists coincides with initial HDM challenge	Neutrophil Migration, cytokines (IL-4,5,9,13,17,10), lung mechanics, Bronchoalveolar lavage cell counts (Eosinophils, neutrophils, macrophages, lymphocytes), various IHC staining for mucus accumulation via PAS	Inflammation: T2R Agonists reduced induction of IL-4,5,13,17, eotaxin, and keratinocyte chemoattractant. Failed to repress TNFα, IP-10, and RANTES. Remodeling: lower collagen deposition and fibronectin expression by taste receptors,. Differential effects in inhibiting matrix metalloproteinases Mechanism Dose dependent reduction in immune cell recruitment by Q and CQ.	CQ and Q differentially inhibited most chemokines and cytokines, Q was overall more effective than CQ at suppressing inflammation.
Howitt et al. (2016) [14••]	Tuft cells, a gut immune cell that can detect parasites, contain taste receptors. Here their downstream signaling pathway is investigated in detail.	WT and TRPM5-/- mice challenged with Tritrichomonas muris (Tm) in a model of helminth infection. Tuft cells were analyzed by IHC + Intestinal organoids cultured to measure Interleukin production. Rag2-/-,Ilr2γ-/- Mice lacking Th2 and ILC2 cells	WT and TRPM5-/- mice, DCLK1+ (tuft cells), intestinal organoids	Interleukin gene expression Flow cytometry cell counting	Upon infection with Tm, TRPM5-/- had reduced IL-25, IL-13, fewer Type2 innate lymphoid cells, and concomitant tuft cell expansion. Additionally,	TRPM5 taste transduction signaling may be used to detect Tm, which excited innate lymphoid type 2 cells (ILC2s), producing IL-13 and thereby promoting their own proliferation