Tryptophan-rich Diet Research Articles

Tryptophan-rich diet and its effects on Htr7+ Tregs in alleviating neuroinflammation and cognitive impairment induced by lipopolysaccharide

BackgroundNeuroinflammation is a vital pathogenic mechanism for neurodegenerative diseases such as Alzheimer’s, schizophrenia, and age-related cognitive decline. Regulatory T cells (Tregs) exhibit potent anti-inflammatory properties and can modulate neurodegenerative diseases arising from central nervous system inflammatory responses. However, the role of Tregs in neuroinflammation-related cognitive dysfunction remains unclear. It is highly plausible that Htr7+ Tregs expressing unique genes associated with the nervous system, including the Htr7 gene encoding the serotonin receptor 5-HT7, play a pivotal role.MethodsMice were given a tryptophan-rich diet (with a tryptophan content of 0.6%) or a normal diet (with a tryptophan content of 0.16%). The neuroinflammation-mediated cognitive dysfunction model was established by intracerebroventricular injection of lipopolysaccharide (LPS) in 8-week-old C57BL/6J mice. The activation and infiltration of Tregs were measured using flow cytometry. Primary Tregs were cocultured separately with primary CD8+ T cells and primary microglia for in vitro validation of the impact of 5-HT and 5-HT7 receptor on Tregs. Prior to their transfer into recombination activating gene 1 (Rag1−/−) mice, Tregs were ex vivo transfected with lentivirus to knock down the expression of Htr7.ResultsIn this study, the tryptophan-rich diet was found to reverse LPS-induced cognitive impairment and reduce the levels of 5-HT in peripheral blood. The tryptophan-rich diet led to increased levels of 5-HT in peripheral blood, which in turn promoted the proliferation and activation of Htr7+ Tregs. Additionally, the tryptophan-rich diet was also shown to attenuate LPS-mediated neuroinflammation by activating Htr7+ Tregs. Furthermore, 5-HT and 5-HT7 receptor were found to enhance the immunosuppressive effect of Tregs on CD8+ T cells and microglia. In Rag1−/− mice, Htr7+ Tregs were shown to alleviate LPS-induced neuroinflammation and cognitive impairment.ConclusionsOur research revealed the ability of Htr7+ Tregs to mitigate neuroinflammation and prevent neuronal damage by suppressing the infiltration of CD8+ T cells into the brain and excessive activation of microglia, thereby ameliorating LPS-induced cognitive impairment. These insights may offer novel therapeutic targets involving Tregs for neuroinflammation and cognitive impairment.

Lactiplantibacillus plantarum DPUL-S164 regulate AhR signaling to ameliorate DSS-induced intestinal barrier damage by producing indole-3-lactic acid in a tryptophan-rich diet

<em>Lactiplantibacillus</em> <em>plantarum</em> DPUL-S164 regulate AhR signaling to ameliorate DSS-induced intestinal barrier damage by producing indole-3-lactic acid in a tryptophan-rich diet

Activated intestinal microbiome-associated tryptophan metabolism upregulates aryl hydrocarbon receptor to promote osteoarthritis in a rat model

To evaluate the role of aryl hydrocarbon receptor in the pathogenesis of osteoarthritis (OA) and its association with intestinal microbiome-related tryptophan metabolism. Cartilage was isolated from OA patients undergoing total knee arthroplasty and analyzed for expression of aryl hydrocarbon receptor (AhR) and cytochrome P450 of family 1, subfamily A, and polypeptide 1 (CyP1A1). To gain mechanistic insights, OA model was induced in Sprague Dawley rats after antibiotic pretreatment combined with a tryptophan-rich diet (or not). The severity of OA was assessed eight weeks after surgery according to the Osteoarthritis Research Society International grading system. Expression of AhR, CyP1A1 as well as markers of bone and cartilage metabolism, inflammation, and intestinal microbiome-related tryptophan metabolism was assessed. Severity of OA in cartilage from patients positively correlated with expression of AhR and CyP1A1 in chondrocytes. In the rat model of OA, antibiotic pretreatment led to lower expression of AhR and CyP1A1 and lower serum levels of lipopolysaccharide (LPS). Conversely, antibiotics upregulated Col2A1 and SOX9 in cartilage, which mitigated the cartilage damage and synovitis, reduced the relative abundance of Lactobacillus. Additional tryptophan supplementation activated intestinal microbiome-related tryptophan metabolism, antagonizing the effects of antibiotics, exacerbating OA synovitis. Our study established an underlying intestinal microbiome associated tryptophan metabolism-OA connection which sets a new target for exploring OA pathogenesis. The alteration of tryptophan metabolism might prompt the activation and synthesis of AhR, accelerating the development of OA.

Tryptophan-rich diet ameliorates chronic unpredictable mild stress induced depression- and anxiety-like behavior in mice: The potential involvement of gut-brain axis

Tryptophan, an essential amino acid, has been reported that it has the potential to regulate depression-like behavior. Meanwhile, Chronic stress-induced depression also has a close relationship with gut microbiota structure and composition. In the current research, we demonstrated that a tryptophan-rich diet (0.6% tryptophan w/w) significantly attenuated depression- and anxiety-like behaviors in a chronic unpredictable mild stress (CUMS)-treated mouse model. Tryptophan supplementation improved neuroinflammation, increased expression of BDNF, and improved mitochondrial energy metabolism in the brain of CUMS-treated mice. Besides, CUMS also enhanced the kynurenine pathway, but repressed the serotonin pathway and indole pathway of tryptophan metabolism, leading to a decrease in 5-HT and indole in serum, whereas tryptophan supplementation might shift the tryptophan metabolism more toward the serotonin pathway in CUMS-treated mice. The gut microbiome was restructured by increasing the relative abundance of Lachnospiracea, Clostridium, Lactobacillus, Bifidobacterium in tryptophan-treated depressive mice. Moreover, tryptophan administration inhibited stress-induced gut barrier damage and decreased inflammatory responses in the colon. Together, our study purports the gut-brain axis as a mechanism for the potential of tryptophan to improve depression and anxiety-related behavior.

Tryptophan-rich diet is negatively associated with depression and positively linked to social cognition

The essential amino acid tryptophan (TRP) is discussed as a potential protective factor for physical and mental health. Besides positive effects via the microbiota of the gut on many physiological processes, TRP is the precursor of the neurotransmitter serotonin (5-HT), thereby playing a role for affective disorders. The present study investigated the effects of a TRP-rich diet on depressiveness and on one of its endophenotypes, impaired social cognition, in a population based sample. N = 482 subjects participated in an online study, assessing the ability to properly recognize emotional states from the eye region of faces (Reading the Mind in the Eye Test, RMET) and asking for subjective ratings of condemnability in a moral judgment task. Moreover, the habitual TRP intake was measured. It was hypothesized that a low-TRP diet is associated with higher depressiveness and worse performance in the social cognition tasks. The main hypotheses could be supported. However, contrary to the expectations, the effect of TRP on social cognition was not mediated by depressiveness. Results show that a tryptophan-rich diet is a potential protective factor against depression and is positively related to functioning in social cognition.

Tryptophan-rich diet can influence sleep quality in different phases of life

Objetivo: Avaliar como a ingestão de triptofano (fontes alimentares e suplementação) influencia o ritmo circadiano e a qualidade do sono de humanos e animais em diferentes faixas etárias. Métodos: Trata-se de uma revisão integrativa da literatura realizada nos Portais de Periódicos PubMed e Capes, considerados no período de 1998 a 2020 nas línguas portuguesa, inglesa e espanhola. A questão norteadora foi: "A ingestão de triptofano através de fontes alimentares e suplementação interfere no ritmo circadiano e na qualidade do sono?”. Os seguintes critérios de inclusão foram utilizados: análise dos descritores (“tryptophan”, “diet”, “sleep”) no título ou resumo do artigo, contextualização da questão norteadora em todo o artigo, tipo de artigo e amostra estudada no artigo. Ao final, 12 artigos foram incluídos no estudo, sendo oito estudos realizados em humanos e quatro em animais. Resultados: Os 12 estudos mostraram que quando a dieta diurna e/ou noturna rica em triptofano, seja por fontes alimentares ou suplementação, é administrada em crianças (n=2), em adultos (n=6), em animais adultos (n=2) e animais jovens e velhos (n=2), houve significativa contribuição para a síntese de serotonina e melatonina. A presença desses mediadores alterou a cronobiologia do ciclo vigília-sono, interferindo na qualidade do sono de humanos e animais. Conclusão: Alimentos que afetam a disponibilidade de triptofano ou sua suplementação e a síntese de serotonina e melatonina foram capazes de organizar o sono dos recém-nascidos, melhorar o sono de adultos e idosos, independentemente dos períodos do dia. Assim, propostas de dietas cronobiologicamente formuladas com triptofano poderiam contribuir para abordagens terapêuticas de baixo custo que contornariam ou reduziriam os distúrbios do sono.

A Case Report: An Unusual Presentation of Purple Urinary Bag Syndrome

Background: The Purple Urinary Bag Syndrome (PUBS) is an uncommon and under-reported syndrome. It results from the purple discoloration of urine by tryptophan-oxidizing bacteria in a favorable alkaline milieu and usually affects patients with indwelling catheters. Other risk factors include female gender, chronic constipation, tryptophan-rich diet, and cognitive impairment. Although asymptomatic in the majority of cases, PUBS may be the sole and earliest sign of an aggressive urinary tract infection, especially in elderly patients where the presentation may be atypical and associated with resistant organisms, such as Pseudomonas aeruginosa and Vancomycin-resistant Enterococci (VRE). Proper treatment consists of catheter replacement and antibiotic therapy, which is indicated only in the setting of symptomatic infections. Case Presentation: We report an unusual presentation of PUBS in a 79-year-old male patient with no classical risk factors. The patient had a supra-pubic catheter for urinary retention secondary to urethral strictures. Every month, by the time of catheter exchange, the patient developed an asymptomatic purple discoloration of the urinary bag, which was not investigated until he presented at our facility. Urine analysis revealed acidic urine. Appropriate antibiotic therapy was initiated after the development of urinary symptoms, and the catheter was replaced. No recurrent urine discoloration occurred. Conclusion: This case represents the rare occurrence of PUBS in the setting of a suprapubic catheter in a male patient. It also highlights that even in atypical presentations, antibiotic therapy should be tailored to the clinical status of the patient and not the mere presence of bacteriuria. Raising awareness about this “esoteric” syndrome is essential for early diagnosis and proper management.

High‐tryptophan Diet Reduces Weight Gain in Rats via Indole‐3‐propionic Acid, a Gut Microbiota Metabolite

Tryptophan is an essential amino acid. Paradoxically, both tryptophan‐low and tryptophan‐rich diets have been found to decrease weight gain in rats, however, the mechanisms are not clear.Energy and water‐electrolyte balance were evaluated in 12‐week‐old, male, Sprague Dawley rats maintained on either control diet (TC) or tryptophan‐high (TH) or tryptophan‐low (TL) or control diet with neomycin, an antibiotic (TCA), for 10 days. Feces and blood levels of tryptophan and its bacterial metabolites were evaluated using chromatography coupled with mass spectrometry.TL rats showed reduction in body weight. TH showed body weight gain, however, it was significantly lower than in TC and TCA rats. TL rats showed significantly lower blood level of tryptophan and its bacterial derivatives including indoxyl sulfate and indole‐3‐propionic acid (I‐3‐P). TH rats had significantly higher blood tryptophan level comparing to TL rats. I‐3‐P in feces and in portal blood of TH rats was significantly higher comparing to TC, TL and TCA rats. In a separate series of experiments rats treated daily i.p. with I‐3‐P showed significantly smaller weight gain than rats treated with the vehicle.Our study suggests that tryptophan‐rich diet has a negative effect on energy balance via I‐3‐P, a gut bacteria metabolite of tryptophan. In contrast, tryptophan‐deficient diet may reduce weight due to the deficiency of the essential amino acid and decreased anabolism.Support or Funding InformationSupported by the Ministry of Science and Higher Education Republic of Poland, Diamond grant DI2016 007346This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Indole-3-Propionic Acid, a Tryptophan-Derived Bacterial Metabolite, Reduces Weight Gain in Rats.

Recent evidence suggests that tryptophan, an essential amino acid, may exert biological effects by means of tryptophan-derived gut bacteria products. We evaluated the potential contribution of tryptophan-derived bacterial metabolites to body weight gain. The study comprised three experimental series performed on separate groups of male, Sprague-Dawley rats: (i) rats on standard laboratory diet treated with water solution of neomycin, an antibiotic, or tap water (controls-1); (ii) rats on standard diet (controls-2) or tryptophan-high (TH) or tryptophan-free (TF) diet; and (iii) rats treated with indole-3-propionic acid (I3P), a bacterial metabolite of tryptophan, or a vehicle (controls-3). (i) Rats treated with neomycin showed a significantly higher weight gain but lower stool and blood concentration of I3P than controls-1. (ii) The TH group showed significantly smaller increases in body weight but higher stool and plasma concentration of I3P than controls-2. In contrast, the TF group showed a decrease in body weight, decreased total serum protein and a significant increase in urine output. (iii) Rats treated with I3P showed significantly smaller weight gain than controls-3. Our study suggests that I3P, a gut bacteria metabolite of tryptophan, contributes to changes in body weight gain produced by antibiotics and tryptophan-rich diet.

Colonic indole, gut bacteria metabolite of tryptophan, increases portal blood pressure in rats.

Portal hypertension (PH) is a potentially life-threatening condition. We investigated the effects of indole and dietary tryptophan, a substrate for gut bacterial production of indole, on portal blood pressure (PBP), portal blood flow (PBF), and arterial blood pressure (ABP) in Sprague-Dawley rats (SD) and SD with PH induced by liver cirrhosis (SD-PH). Hemodynamics were recorded in anesthetized male 28-wk-old SD and SD-PH at baseline and after the administration of either a vehicle or indole into the colon. Blood levels of tryptophan and its bacterial metabolites were evaluated using chromatography coupled with mass spectrometry. Indole at lower doses increased PBP and PBF. Indole at higher doses produced a transient increase in PBP, which was accompanied by a decrease in ABP. Portal blood levels of indole, indole-3-propionic, indole-3-lactic, and indole-3-acetic acids were higher in SD-PH, suggesting an increased gut-blood barrier permeability. Rats on a tryptophan-rich diet showed a significantly higher PBP and portal blood level of indoles than rats on a tryptophan-free diet. In conclusion, a tryptophan-rich diet and intracolonic indole increase PBP and portal blood level of indole. Rats with PH show an increased penetration of indoles from the colon to the circulation. Intracolonic indole production may be of therapeutic importance in PH.

Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells

Abstract The small intestine contains CD4+CD8αα+ double-positive intraepithelial T lymphocytes (DP IELs), which originate from intestinal CD4+T cells through downregulation of the transcription factor ThpoK and have regulatory functions. DP IELs are absent in germ-free mice, suggesting that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri. This species induced DP IELs in germ-free mice and conventionally-raised mice lacking these cells. L. reuteri did not shape DP-IEL-TCR repertoire, but generated indol derivatives of tryptophan that activated the aryl-hydrocarbon receptor in CD4+ T cells, allowing ThPOK downregulation and differentiation into DP IELs. Thus, L. reuteri together with a tryptophan-rich diet can reprogram intraepithelial CD4+ T cells into immunoregulatory T cells.

Lactobacillus reuteri induces gut intraepithelial CD4+CD8αα+ T cells.

The small intestine contains CD4+CD8αα+ double-positive intraepithelial lymphocytes (DP IELs), which originate from intestinal CD4+ T cells through down-regulation of the transcription factor Thpok and have regulatory functions. DP IELs are absent in germ-free mice, which suggests that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri This species induced DP IELs in germ-free mice and conventionally-raised mice lacking these cells. L. reuteri did not shape the DP-IEL-TCR (TCR, T cell receptor) repertoire but generated indole derivatives of tryptophan that activated the aryl-hydrocarbon receptor in CD4+ T cells, allowing Thpok down-regulation and differentiation into DP IELs. Thus, L. reuteri, together with a tryptophan-rich diet, can reprogram intraepithelial CD4+ T cells into immunoregulatory T cells.

Daily profiles of serum and gastrointestinal melatonin in response to daytime or night-time supply of tryptophan-rich diet in carp (Catla catla)

Influences of daytime (~10:00 h) or night-time (~22:00 h) supply of L-tryptophan (Trp)-rich diet on daily rhythm features of melatonin and arylalkylamine-N-acetyltransferase (AANAT) protein (key regulator of melatonin biosynthesis) in gastrointestinal (gut) tissue extracts, and melatonin in serum were studied in carp (Catla catla). Analysis of obtained data revealed that the mesor and amplitude values of both melatonin and AANAT in gut tissue-extracts were higher in daytime-fed fish than those supplied with food at night, and their acrophase varied from ~2 h in the daytime-fed carp to ~10 h in night-time-fed fish. Notably, initiation of stimulatory response of melatonin and AANAT in gut to Trp-rich diet varied from ~2 h (following food supply in day) to ~6 h (after food supply during night). However, in either case, their elevated levels were maintained for ~12 h. Trp-rich diet also caused increase in serum melatonin levels, and the duration of such response varied with the time of food supply. Collectively, present study not only demonstrates the role of Trp-rich diet as a potential inducer of gut melatoninergic system and modulator of daily serum melatonin profiles, but underlines the importance of the time of food supply as a determining factor of its influence as well.

Effect of diet on serotonergic neurotransmission in depression

Depression is characterized by sadness, purposelessness, irritability, and impaired body functions. Depression causes severe symptoms for several weeks, and dysthymia, which may cause chronic, low-grade symptoms. Treatment of depression involves psychotherapy, medications, or phototherapy. Clinical and experimental evidence indicates that an appropriate diet can reduce symptoms of depression. The neurotransmitter, serotonin (5-HT), synthesized in the brain, plays an important role in mood alleviation, satiety, and sleep regulation. Although certain fruits and vegetables are rich in 5-HT, it is not easily accessible to the CNS due to blood brain barrier. However the serotonin precursor, tryptophan, can readily pass through the blood brain barrier. Tryptophan is converted to 5-HT by tryptophan hydroxylase and 5-HTP decarboxylase, respectively, in the presence of pyridoxal phosphate, derived from vitamin B6. Hence diets poor in tryptophan may induce depression as this essential amino acid is not naturally abundant even in protein-rich foods. Tryptophan-rich diet is important in patients susceptible to depression such as certain females during pre and postmenstrual phase, post-traumatic stress disorder, chronic pain, cancer, epilepsy, Parkinson’s disease, Alzheimer’s disease, schizophrenia, and drug addiction. Carbohydrate-rich diet triggers insulin response to enhance the bioavailability of tryptophan in the CNS which is responsible for increased craving of carbohydrate diets. Although serotonin reuptake inhibitors (SSRIs) are prescribed to obese patients with depressive symptoms, these agents are incapable of precisely regulating the CNS serotonin and may cause life-threatening adverse effects in the presence of monoamine oxidase inhibitors. However, CNS serotonin synthesis can be controlled by proper intake of tryptophan-rich diet. This report highlights the clinical significance of tryptophan-rich diet and vitamin B6 to boost serotonergic neurotransmission in depression observed in various neurodegenerative diseases. However pharmacological interventions to modulate serotonergic neurotransmission in depression, remains clinically significant. Depression may involve several other molecular mechanisms as discussed briefly in this report.

Phthalate esters enhance quinolinate production by inhibiting amino-carboxymuconate-semialdehyde decarboxylase (ACMSD), a key enzyme of the tryptophan-niacin pathway

Tryptophan is metabolized to a-amino-b-carboxymuconate-«semialdehyde (ACMS) via 3-hydroxyanthranilate (3-HA). ACMS decarboxylase (ACMSD) directs ACMS to acetyl CoA; otherwise ACMS is non-enzymatically converted to quinolinate (QA), leading to the formation of NAD and its degradation products. Thus, ACMSD is a critical enzyme for tryptophan metabolism. Phthalate esters have been suspected of being environmental endocrine disrupters. Because of the structural similarity of phthalate esters with tryptophan metabolites, we examined the effects of phthalate esters on tryptophan metabolism. Phthalate esters containing diets were orallygiventoratsandtheurinaryexcretedtryptophanmetabolites were quantified. Of the phthalate esters with different side chains tested, di(2-ethylhexyl)phthalate (DEHP) and its metabolite, mono(2-ethylhexyl)phthalate (MEHP), most strongly enhanced the production of QA and degradation products of nicotinamide, while3-HAwasunchanged.Thispatternofmetabolicchangeledus to assume that these esters lowered ACMSD protein or its activity. Although DEHP could not be tested because of its low solubility, MEHP reversibly inhibited ACMSD from rat liver and mouse kidney, andalso the recombinanthuman enzyme. Correlationbetween inhibition of ACMSD by phthalate esters with different side chains and urinary excretion of QA supports the notion that phthalate esters perturb tryptophan metabolism by inhibiting ACMSD. Quinolinate is a potential endogenous toxin and has been implicated in thepathogenesisofvariousdisorders.Althoughtoxicityofphthalate esters through accumulation of QA remains to be investigated, they may be detrimental by acting as metabolic disrupters when intake of a tryptophan-rich diet and exposure to phthalate esters occur coincidentally.

Phthalate esters enhance quinolinate production by inhibiting alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD), a key enzyme of the tryptophan pathway.

Tryptophan is metabolized to alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) via 3-hydroxyanthranilate (3-HA). ACMS decarboxylase (ACMSD) directs ACMS to acetyl CoA; otherwise ACMS is non-enzymatically converted to quinolinate (QA), leading to the formation of NAD and its degradation products. Thus, ACMSD is a critical enzyme for tryptophan metabolism. Phthalate esters have been suspected of being environmental endocrine disrupters. Because of the structural similarity of phthalate esters with tryptophan metabolites, we examined the effects of phthalate esters on tryptophan metabolism. Phthalate esters containing diets were orally given to rats and the urinary excreted tryptophan metabolites were quantified. Of the phthalate esters with different side chains tested, di(2-ethylhexyl)phthalate (DEHP) and its metabolite, mono(2-ethylhexyl)phthalate (MEHP), most strongly enhanced the production of QA and degradation products of nicotinamide, while 3-HA was unchanged. This pattern of metabolic change led us to assume that these esters lowered ACMSD protein or its activity. Although DEHP could not be tested because of its low solubility, MEHP reversibly inhibited ACMSD from rat liver and mouse kidney, and also the recombinant human enzyme. Correlation between inhibition of ACMSD by phthalate esters with different side chains and urinary excretion of QA supports the notion that phthalate esters perturb tryptophan metabolism by inhibiting ACMSD. Quinolinate is a potential endogenous toxin and has been implicated in the pathogenesis of various disorders. Although toxicity of phthalate esters through accumulation of QA remains to be investigated, they may be detrimental by acting as metabolic disrupters when intake of a tryptophan-rich diet and exposure to phthalate esters occur coincidentally.

Tryptophan rich diet as a new approach to study the serotoninergic enteropancreatic axis.

The influence of a tryptophan enriched diet (L-tryptophan added as 1% of total diet), fed over 10 days, on the rat duodenum and pancreas was studied by immunohistology, measurements of serotonin and tryptophan tissue concentrations by HPLC, and incubations of pancreatic lobules. Ingestion of a tryptophan enriched diet resulted in increased contents of tryptophan and serotonin in the duodenum that was not accompanied by a significant change of the serotonin cell density. Neither basal nor CCK-stimulated amylase release from isolated pancreatic lobules was altered after tryptophan enriched food. Although serotonin could be extracted from the pancreas, no increase in serotonin concentration was detected after ingestion of the tryptophan diet. A 'serotonin loading' diet may be a useful tool to study the significance of amines produced by gut endocrine cells in respects to enteropancreatic connections.