About

Mariana Silva is a Teaching Associate Professor in the Siebel School of Computing and Data Science at the University of Illinois Urbana-Champaign. She holds a Ph.D. in Theoretical and Applied Mechanics from the University of Illinois, earned in 2009, and has a background in mechanical engineering with a Bachelor's and Master's degree from the Federal University of Rio de Janeiro, Brazil. Silva is also the co-founder and CEO of PrairieLearn Inc., a company dedicated to providing tools to enhance teaching workflows in education. Her research focuses on leveraging educational technologies to improve computer-based assessments and centralized testing centers. This includes the use of Large Language Models for automated grading and creating robust, randomized question generators to promote equity, accessibility, and scalability in teaching, learning, and testing practices. Silva has extensive experience in course development across engineering, computer science, and mathematics, and is passionate about advancing teaching innovations that benefit both students and instructors. Her doctoral research involved the theory, computation, and design optimization of systems governed by partial differential equations, addressing challenges in structural topology optimization, material design, energy mitigation, fracture mechanics, and robust optimization.

Research topics

• Chemistry
• Biology
• Biochemistry
• Pharmacology
• Medicine
• Immunology
• Computer Science
• Organic chemistry
• Food science
• Composite material
• Cell biology
• Radiology
• Endocrinology
• Materials science
• Environmental chemistry

Selected publications

• Obesity-associated memory impairment and neuroinflammation precede widespread peripheral perturbations in aged rats

  Immunity & Ageing · 2025-01-03 · 14 citations

  articleOpen access

  BACKGROUND: Obesity and metabolic syndrome are major public health concerns linked to cognitive decline with aging. Prior work from our lab has demonstrated that short-term high fat diet (HFD) rapidly impairs memory function via a neuroinflammatory mechanism. However, the degree to which these rapid inflammatory changes are unique to the brain is unknown. Moreover, deviations in gut microbiome composition have been associated with obesity and cognitive impairment, but how diet and aging interact to impact the gut microbiome, or how rapidly these changes occur, is less clear. Thus, our study investigated the impact of HFD after two distinct consumption durations: 3 months (to model diet-induced obesity) or 3 days (to detect the rapid changes occurring with HFD) on memory function, anxiety-like behavior, central and peripheral inflammation, and gut microbiome profile in young and aged rats. RESULTS: Our data indicated that both short-term and long-term HFD consumption impaired memory function and increased anxiety-like behavior in aged, but not young adult, rats. These behavioral changes were accompanied by pro- and anti-inflammatory cytokine dysregulation in the hippocampus and amygdala of aged HFD-fed rats at both time points. However, changes to fasting glucose, insulin, and inflammation in peripheral tissues such as the distal colon and visceral adipose tissue were increased in young and aged rats only after long-term, but not short-term, HFD consumption. Furthermore, while subtle HFD-induced changes to the gut microbiome did occur rapidly, robust age-specific effects were only present following long-term HFD consumption. CONCLUSIONS: Overall, these data suggest that HFD-evoked neuroinflammation, memory impairment, and anxiety-like behavior in aging develop quicker than, and separately from the peripheral hallmarks of diet-induced obesity.

  PublisherOA PDFDOI

• Social stress worsens colitis through β-adrenergic–driven oxidative stress in intestinal mucosal compartments

  Brain Behavior and Immunity · 2025-12-17 · 1 citations

  articleOpen access1st authorCorresponding

  Psychological stress is a known risk factor for inflammatory bowel disease (IBD), but the mechanisms linking stress to worsened disease remain unclear. Because distinct stress paradigms activate different neuroimmune circuits, it is critical to investigate model-specific effects. We examined how social stress primes the gut for heightened inflammation and whether this is mediated by specific neuroendocrine pathways, including α2-/β-adrenergic (sympathetic) or glucocorticoid/ corticotropin-releasing hormone receptor (CRHR1) (HPA axis) signaling. Mice were exposed to social disruption (SDR) stress and pre-treated with pharmacological antagonists targeting α2-adrenergic receptors (idazoxan), β-adrenergic receptor (β-AR) (propranolol), glucocorticoid receptor (mifepristone), or CRHR1 (antalarmin). Intestinal epithelial cell (IEC) gene expression and microbiota composition were assessed following SDR. To determine disease impact, SDR was combined with either Citrobacter rodentium infection or dextran sulfate sodium (DSS)-induced colitis, with interventions including the β-AR inhibitors and the NADPH oxidase inhibitor apocynin. SDR significantly upregulated expression of Dual oxidase 2 (Duox2), Dual oxidase maturation factor 2 (Duoxa2), and inducible nitric oxide synthase 2 (Nos2) in IECs (2- to 8-fold, p < 0.0001), effects reversed by β-AR blockade but not α2-adrenergic, CRH, or glucocorticoid inhibition. SDR also induced microbial dysbiosis, characterized by reduced α -diversity and compositional shifts, which was rescued by propranolol. Stress exacerbated disease severity in both infectious (C. rodentium) and chemically induced (DSS) colitis, amplifying colonic expression of Duox2, Nos2, and Ccl2, especially. Apocynin mitigated stress-induced ROS/RNS production and body weight loss even prior to colitis onset, reduced colonic expression of key oxidative enzymes, especially DUOX2, and alleviated both chemically and infectious colitis severity. These findings provide strong evidence that social stress sensitizes the gut to inflammation through β-adrenergic and NADPH oxidase-driven oxidative stress, highlighting potential therapeutic targets for mitigating stress-exacerbated IBD.

  PublisherDOI

• Age-related Changes in Intestinal Sphingolipid Metabolism and Microbiota-dependent Lipid Absorption

  Physiology · 2025-05-01 · 1 citations

  article

  Aging is a degenerative process linked to increased inflammation and dysfunction of the intestinal epithelial barrier, which may impact nutrient absorption in the rapidly growing elderly population. Emerging evidence suggests that disruptions in intestinal host-microbiota crosstalk sphingolipids (SLs) may precede the decline in immune function and intestinal nutrient absorption observed with aging, but the mechanisms associated with this disruption remain poorly defined. Given the pivotal role of intestinal SL in regulating lipid metabolism and inflammation, we propose that age-related inflammation and reduced barrier integrity are linked to alterations in host-microbiota SL metabolism. Here, we utilized Liquid Chromatography/Mass Spectrometry (LC/MS)-based lipidomics to identify colonic digesta lipid alterations with aging in C57BL/6 mice (young= 3-4 m.o. vs. aged= 18-20 m.o.). First, we revealed that gut SL metabolism is robustly altered with age, hallmarked by the accumulation of numerous SLs and ceramides (Cer). Next, we investigated small intestinal expression of fatty acid (FA) synthesis and trafficking genes ( Fasn, Acc2, Elovl6, Cd36 , ApoB ) but did not observe significant differences. However, among SL metabolism genes ( Sptlc1, 2, Cers2 ,4, 6, Kdsr , Degs1,2 ), Cers6 was significantly higher ( p &lt;0.01) in small intestine of young mice, which may indicate a greater synthesis of barrier ceramides that declines with age. Further, higher accumulation of SLs in digesta are strongly associated with signs of immune cell infiltration like calprotectin ( p &lt;0.0001) and ex vivo immune toll-like receptor TLR4 reactivity of intestinal mucosa ( p &lt;0.05) and feces ( p &lt;0.001). Given that aging is associated with reduced intestinal resilience, we examined the effect of broad-spectrum antibiotic cocktail (ABX) challenge in young and aged mice. Following a one-week of ABX, mice were allowed to recover for 1 week washout period. Expression of FA and SL metabolism genes in the ileum was unaltered by ABX treatment after washout. Despite this, ABX exposure led to a robust accumulation of digesta triglycerides (TG) in aged mice after washout, indicating a heightened lipid malabsorptive phenotype with aging. Moreover, ABX-induced TG accumulation in the colon of aged mice is associated with an inability to recover their microbiome structure and persistent TLR4 immunogenicity of the digesta. Our findings are in line with a previous aged germ-free (GF) mouse (vs. specific pathogen-free mice; SPF) lipidomic analysis by Tsugawa, et al. ( Nature Aging, 2024), which shows greater SL accumulation in small intestine tissue during aging, with non-glycosylated SLs dominating in SPF mice and glycosylated SLs in GF mice, highlighting the role of gut microbiota in intestinal lipid homeostasis. Altogether, we show that aging and ABX disrupt intestinal lipids which may underlie the chronic inflammatory milieu and reduced barrier integrity. Future studies are needed to understand how aging disrupts intestinal host-microbiota lipid metabolism and nutrient absorption. Funding was provided by Vision 20/20 at the University of Illinois Urbana-Champaign This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Total Protein

  Methods and protocols in food science · 2025-01-01

  book-chapter1st authorCorresponding
  PublisherDOI

• The aged amygdala’s unique sensitivity to refined diets, independent of fat or sugar content: A brain region and cell type-specific analysis

  Brain Behavior and Immunity · 2025-12-10 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• Indoleamine 2, 3 dioxygenase (IDO1) differentiallyModulates Microbial Aromatic Amino Acid Metabolites and Colonic Inflammation in an Age-Dependent Manner

  Physiology · 2025-05-01 · 1 citations

  article

  Background and Objective: Indoleamine 2,3-dioxygenase (IDO1) metabolizes tryptophan (Trp) into kynurenine (Kyn), an immunosenescence pathway linked to immune dysfunction in aging, though its mechanism remains unclear. Kynurenine activates aryl hydrocarbon receptor (AHR) which further regulates immunity and gut homeostasis by shaping the microbiota. H350A transgenic mice that express IDO1 but are incapable of IDO1 Trp metabolism show distinct immune responses compared to constitutional IDO1 knockout (IDOKO) mice, confirming that IDO1 possesses both enzyme- and non-enzyme-dependent functions. Gut microbes also metabolize aromatic amino acids including Trp, tyrosine (Tyr), and phenylalanine (Phe) into bioactive aryl metabolites that influence IDO1-driven immune responses. We examined how age and IDO1 activity interact to influence the gut microbiome, microbrial-derived aryl metabolites, and colonic inflammation across the lifespan. Hypothesis: Microbial aryl metabolites are lower in WT mice as compared to IDOKO and H350A (IDO1 enzyme null) mice, and in-turn, intestinal inflammation is increased in WT as compared to IDOKO and H350A mice during advanced age. Methods: Serum, ileal content, and colonic content of young 12 –22-week-old WT, H350A, and IDOKO mice, (n=6-8/group) and old 114-138 week old (n=10/group) wwere analyzed for microbial aryl metabolites by LC/MS/MS. Microbe compositionof ileum and colon contents were assessed by 16S rRNA sequencing. Inflammatory markers were assessedin ileum and colon tissues by multiplex qPCR. Results: Tryptophan-derived microbial aryl metabolites, indole-lactate and indole-acetatein aged WT mice as compared to IDOKO or H350A mice (p&lt;0.05).Immune-modulating Tyr-derived 4-hydroxyphenyllactic acid (4-HPLA) and Phe-derived phenyllactate (PLA), were also increased in the serum of aged IDOKO and H350A mice (p&lt;0.05) as compared to aged WT mice. A known microbial derived anti-inflammatory aryl metabolite producer, Bifidobacterium sp, was increased in the colon of young and aged IDOKO mice and also in the ileum of H350A mice compared to WT mice. In contrast, the pro-inflammatory pathobiont, Helicobacter hepaticus, was elevated in the colon of both IDOKO and H350A aged mice compared to aged WT mice, correlating to increased colonic inflammatory markers (Lbp, Tnfrsf1b, S100a8, S100a9, and Ccr2). Conclusion: Enzymatic and non-enzymatic activity of IDO1 influences microbial-derived aryl production, microbiota composition, and colonic inflammation, with effects more pronounced in aging. IDO1 deficiency (genetic/metabolic) alters gut microbial metabolism, with protective consequences depending on microbiota composition.Ongoing studies are examining the role of AHRin mediating IDO1-dependent and independent regulation of gut microbiota and inflammation. This work was supported in part by National Institutes of Health (NIH) grants R01NS097851 (D.A.W.), K02AG068617 (D.A.W.), R01NS129835 (D.A.W.), RO1DK131133 (J.M.A) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Ingestion of Fermented Food-Associated Microbial Aryl Metabolites Attenuates High Fat Diet-Induced Liver Lipid Accumulation

  Physiology · 2025-05-01

  article

  Objective: Consumption of fermented foods is associated with lower systemic inflammation and improved metabolic health, yet the underlying mechanisms remain unclear. We investigated if microbial-derived aromatic amino acid metabolites found in fermented foods, specifically phenyllactic acid (PLA), 4-hydroxyphenyllactic acid (4HPLA), and indole-3-lactic acid (ILA), collectively termed aryl-lactates (AL), mitigate liver fat accumulation, a key marker of metabolic-associated steatotic liver disease (MASLD). We also assessed their effects on macrophage phagocytic activity ex vivo. Hypothesis: We hypothesized that AL reduce weight gain and hepatic lipid accumulation when consumed at doses found in fermented foods. Methods: 12-week-old; C57BL/6 male mice were fed either control diet (CD; 15% kcal fat) or high-fat diet (HFD; 45% kcal fat) and provided a combination of AL (4HPLA+PLA+ILA) (0 or 10 µM/d total) in drinking water (n=6/group) for 16 weeks. Body weight, food intake, and water consumption were recorded 3 times/wk. Body composition was analyzed with EchoMRI at wks 8 and 15. After 16 weeks, liver weight was recorded, and hepatic lipid accumulation was assessed via Oil Red O staining. To evaluate the effect of AL on macrophage function, we performed ex vivo assays using macrophages differentiated from human peripheral blood mononuclear cells exposed to 0 or 50 µM of either 4HPLA, ILA, or PLA. Phagocytic activity was assessed using fluorescein stained, lyophilized E. Coli particles. Results: Weight gain, fat mass, and liver weight were increased for HFD compared to CD fed mice. AL decreased weight gain, fat mass, liver weight, and increased lean mass of only HFD fed mice (p&lt;0.05). Additionally, AL attenuated HFD-induced hepatic lipid accumulation (p&lt;0.05). Given the critical role of macrophages in MASLD progression, we examined if these effects were associated with enhanced macrophage function. Ex vivo treatment of macrophages with any of the three AL increased macrophage phagocytosis (p&lt;0.05) with 4HPLA being the most effective. Result summary: AL reduced weight gain, fat mass, and hepatic lipid accumulation of HFD-fed mice. Conclusion: Ingestion of microbial-derived aryl-lactates limited fat accumulation in the liver in response to HFD. Ongoing studies aim to further elucidate the mechanistic contributions of macrophages in this process. These findings highlight the therapeutic potential of fermented food-derived microbial metabolites in mitigating MASLD severity. Funding: USDA-AFRI- 2023-67017-39053 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Social stress worsens colitis through β-adrenergic–driven oxidative stress in intestinal mucosal compartments

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-07-18 · 1 citations

  preprintOpen access1st authorCorresponding

  Abstract Psychological stress is a known risk factor for inflammatory bowel disease (IBD), but the mechanisms linking stress to worsened disease remain unclear. Because distinct stress paradigms activate different neuroimmune circuits, it is critical to investigate model-specific effects. We examined how social stress primes the gut for heightened inflammation and whether this is mediated by specific neuroendocrine pathways, including α2-/β-adrenergic (sympathetic) or glucocorticoid/ corticotropin-releasing hormone receptor (CRHR1) (HPA axis) signaling. Mice were exposed to social disruption (SDR) stress and pre- treated with pharmacological antagonists targeting α2-adrenergic receptors (idazoxan), β-adrenergic receptor (β-AR) (propranolol), glucocorticoid receptor (mifepristone), or CRHR1 (antalarmin). Intestinal epithelial cell (IEC) gene expression and microbiota composition were assessed following SDR. To determine disease impact, SDR was combined with either Citrobacter rodentium infection or dextran sulfate sodium (DSS)-induced colitis, with interventions including the β-AR inhibitor propranolol and the NADPH oxidase inhibitor apocynin. SDR significantly upregulated expression of Dual oxidase 2 (Duox2) , Dual oxidase maturation factor 2 (Duoxa2) , and inducible nitric oxide synthase 2 (Nos2) in IECs (2- to 8- fold, p &lt; 0.0001), effects reversed by β-AR blockade but not α2-adrenergic, CRH, or glucocorticoid inhibition. SDR also induced microbial dysbiosis, characterized by reduced alpha-diversity and compositional shifts, which was rescued by propranolol. Stress exacerbated disease severity in both infectious ( C. rodentium ) and chemically induced (DSS) colitis, amplifying colonic expression of Duox2 , Nos2 , and Ccl2, especially. Apocynin mitigated stress-induced ROS/RNS production and body weight loss even prior to colitis onset, reduced colonic gene expression of key oxidative enzymes, and alleviated both chemically and infectious colitis severity. These findings provide strong evidence that social stress sensitizes the gut to inflammation through β-adrenergic and NADPH oxidase–driven oxidative stress, highlighting potential therapeutic targets for mitigating stress-exacerbated IBD. Highlights Social disruption (SDR) and restraint stress (RST) activate distinct neuroendocrine pathways, with SDR driving epithelial ROS/RNS pathways via β-adrenergic signaling. β-adrenergic blockade prevents SDR-induced epithelial priming, microbial dysbiosis, and colitis exacerbation. NADPH oxidase inhibition with apocynin mitigates stress-induced oxidative stress and disease severity across different colitis models. Findings identify β-adrenergic and redox pathways as therapeutic targets for stress-exacerbated IBD.

  PublisherDOI

• The emergence of inflammatory microglia during gut inflammation is not affected by FFAR2 expression in intestinal epithelial cells or peripheral myeloid cells

  Brain Behavior and Immunity · 2024-03-11 · 18 citations

  articleOpen access1st author

  Gut inflammation can trigger neuroinflammation and is linked to mood disorders. Microbiota-derived short-chain fatty acids (SCFAs) can modulate microglia, yet the mechanism remains elusive. Since microglia do not express free-fatty acid receptor (FFAR)2, but intestinal epithelial cells (IEC) and peripheral myeloid cells do, we hypothesized that SCFA-mediated FFAR2 activation within the gut or peripheral myeloid cells may impact microglia inflammation. To test this hypothesis, we developed a tamoxifen-inducible conditional knockout mouse model targeting FFAR2 exclusively on IEC and induced intestinal inflammation with dextran sodium sulfate (DSS), a well-established colitis model. Given FFAR2's high expression in myeloid cells, we also investigated its role by selectively deleting it in these populations of cells. In an initial study, male and female wild-type mice received 0 or 2% DSS for 5d and microglia were isolated 3d later to assess inflammatory status. DSS induced intestinal inflammation and upregulated inflammatory gene expression in microglia, indicating inflammatory signaling via the gut-brain axis. Despite the lack of significant effects of sex in the intestinal phenotype, male mice showed higher microglial inflammatory response than females. Subsequent studies using FFAR2 knockout models revealed that FFAR2 expression in IECs or immune myeloid cells did not affect DSS-induced colonic pathology (i.e. clinical and histological scores and colon length), or colonic expression of inflammatory genes. However, FFAR2 knockout led to an upregulation of several microglial inflammatory genes in control mice and downregulation in DSS-treated mice, suggesting that FFAR2 may constrain neuroinflammatory gene expression under healthy homeostatic conditions but may permit it during intestinal inflammation. No interactions with sex were observed, suggesting sex does not play a role on FFAR2 potential function in gut-brain communication in the context of colitis. To evaluate the role of FFAR2 activated by microbiota-derived SCFAs, we employed the same knockout and DSS models adding fermentable dietary fiber (0 or 2.5% inulin for 8 wks). Despite no genotype or fiber main effects, contrary to our hypothesis, inulin feeding augmented DSS-induced inflammation and signs of colitis, suggesting context-dependent effects of fiber. These findings highlight microglial involvement in colitis-associated neuroinflammation and advance our understanding of FFAR2's role in the gut-brain axis. Although not integral, we observed that the role of FFAR2 differs between homeostatic and inflammatory conditions, underscoring the need to consider different inflammatory conditions and disease contexts when investigating the role of FFAR2 and SCFAs in the gut-brain axis.

  PublisherDOI

• Aging amplifies a gut microbiota immunogenic signature linked to heightened inflammation

  Aging Cell · 2024-05-09 · 37 citations

  articleOpen access1st author

  Aging is associated with low-grade inflammation that increases the risk of infection and disease, yet the underlying mechanisms remain unclear. Gut microbiota composition shifts with age, harboring microbes with varied immunogenic capacities. We hypothesized the gut microbiota acts as an active driver of low-grade inflammation during aging. Microbiome patterns in aged mice strongly associated with signs of bacterial-induced barrier disruption and immune infiltration, including marked increased levels of circulating lipopolysaccharide (LPS)-binding protein (LBP) and colonic calprotectin. Ex vivo immunogenicity assays revealed that both colonic contents and mucosa of aged mice harbored increased capacity to activate toll-like receptor 4 (TLR4) whereas TLR5 signaling was unchanged. We found patterns of elevated innate inflammatory signaling (colonic Il6, Tnf, and Tlr4) and endotoxemia (circulating LBP) in young germ-free mice after 4 weeks of colonization with intestinal contents from aged mice compared with young counterparts, thus providing a direct link between aging-induced shifts in microbiota immunogenicity and host inflammation. Additionally, we discovered that the gut microbiota of aged mice exhibited unique responses to a broad-spectrum antibiotic challenge (Abx), with sustained elevation in Escherichia (Proteobacteria) and altered TLR5 immunogenicity 7 days post-Abx cessation. Together, these data indicate that old age results in a gut microbiota that differentially acts on TLR signaling pathways of the innate immune system. We found that these age-associated microbiota immunogenic signatures are less resilient to challenge and strongly linked to host inflammatory status. Gut microbiota immunogenic signatures should be thus considered as critical factors in mediating chronic inflammatory diseases disproportionally impacting older populations.

  PublisherOA PDFDOI

Frequent coauthors

• Maria Teresa Bertoldo Pacheco

  25 shared

• Nádia Fátima Gibrim

  13 shared

• Valdemiro Carlos Sgarbieri

  Universidade Estadual de Campinas (UNICAMP)

  13 shared

• Denise Aparecida Gonçalves de Oliveira

  Universidade Paulista

  13 shared

• Jacob M. Allen

  University of Illinois Urbana-Champaign

  10 shared

• Pedro Esteves Duarte Augusto

  Université Paris-Saclay

  9 shared

• Laurie A. Rund

  9 shared

• Jeffrey A. Woods

  University of Illinois Urbana-Champaign

  9 shared

Labs

• Siebel School of Computing and Data SciencePI

Education

• PhD in Food and Nutrition, Department of Food and Nutrition

  State University of Campinas

  2017

• M.Sc. in Food and Nutrition, Department of Food and Nutrition

  State University of Campinas

  2013

• BsC in Food Science

  University of São Paulo (USP)

  2011

• Technician, Technical College of Campinas

  State University of Campinas

  2006

Awards & honors

• Celebration of Excellence 2023
• Celebration of Excellence 2022
• Celebration of Excellence 2021