Waste to protein: A systematic review of a century of advancement in microbial fermentation of agro-industrial byproducts.

Increasing global consumption of protein over the last five decades, coupled with concerns about the impact on emissions of animal-based protein production, has created interest in alternative protein sources. Microbial proteins (MPs), derived through the fermentation of agro-industrial byproducts, present a promising option. This review assesses a century of advancements in this domain. We conducted a comprehensive review and meta-analysis, examining 347 relevant research papers to identify trends, technological advancements, and key influencing factors in the production of MP. The analysis covered the types of feedstocks and microbes, fermentation methods, and the implications of nucleic acid content on the food-grade quality of proteins. A conditional inference tree model and Bayesian factor were used to ascertain the impact of various parameters on protein content. Out of all the studied parameters, such as type of feedstock (lignocellulose, free sugars, gases, and others), type of fermentation (solid, liquid, gas), type of microbe (bacteria, fungi, yeast, and mix), and operating parameters (temperature, time, and pH), the type of fermentation and microbe were identified as the largest influences on protein content. Gas and liquid fermentation demonstrated higher protein content, averaging 52% and 42%, respectively. Among microbes, bacterial species produced a higher protein content of 51%. The suitable operating parameters, such as pH, time, and temperature, were also identified for different microbes. The results point to opportunities for continued innovation in feedstock, microbes, and regulatory alignment to fully realize the potential of MP in contributing to global food security and sustainability goals.

Interaction of the Gut Microbiome and Immunity in Multiple Sclerosis: Impact of Diet and Immune Therapy.

The bidirectional communication between the gut and central nervous system (CNS) through microbiota is known as the microbiota-gut-brain axis. The brain, through the enteric neural innervation and the vagus nerve, influences the gut physiological activities (motility, mucin, and peptide secretion), as well as the development of the mucosal immune system. Conversely, the gut can influence the CNS via intestinal microbiota, its metabolites, and gut-homing immune cells. Growing evidence suggests that gut immunity is critically involved in gut-brain communication during health and diseases, including multiple sclerosis (MS). The gut microbiota can influence the development and function of gut immunity, and conversely, the innate and adaptive mucosal immunity can influence microbiota composition. Gut and systemic immunity, along with gut microbiota, are perturbed in MS. Diet and disease-modifying therapies (DMTs) can affect the composition of the gut microbial community, leading to changes in gut and peripheral immunity, which ultimately affects MS. A high-fat diet is highly associated with gut dysbiosis-mediated inflammation and intestinal permeability, while a high-fiber diet/short-chain fatty acids (SCFAs) can promote the development of Foxp3 Tregs and improvement in intestinal barrier function, which subsequently suppress CNS autoimmunity in the animal model of MS (experimental autoimmune encephalomyelitis or EAE). This review will address the role of gut immunity and its modulation by diet and DMTs via gut microbiota during MS pathophysiology.

Land gradient and configuration effects on yield, irrigation amount and irrigation water productivity in rice-wheat and maize-wheat cropping systems in Eastern India.

Laser land levelling is expanding rapidly in the rice-wheat (RW) and maize-wheat (MW) systems of the Indo-Gangetic Plains of India and Pakistan. Current practice is to level to zero (0%) gradient, whereas a small gradient (e.g. 0.1%) is typically used in developed countries. Therefore, experiments were conducted in farmers' plots (~15 m x 40 m) in the Eastern Gangetic Plains to evaluate laser levelling with a 0.1% gradient in comparison with 0% and farmer levelling practice (FL). The study was conducted over two years in RW and MW systems. In the MW system, raised beds in plots lasered with 0% and 0.1% gradients were also evaluated. Laser levelling with 0% gradient significantly reduced irrigation amount and/or increased irrigation water productivity (WPi) in all crops/systems grown on the flat compared to FL except for wheat in the MW system. While there was a consistent trend for higher yield with a 0% gradient compared with FL, the differences were not significant in any crop/system. For the RW system, the results suggest no to marginal benefits in irrigation amount and WPi from levelling with a 0.1% gradient in comparison with 0% gradient. In that system, by far the bigger gains were from changing from FL to laser levelling with 0% gradient. This resulted in substantial reductions in irrigation amount, which greatly increased WPi in both crops (by ~40%), while yield was not affected. Rice grown with FL was not profitable, but lasering with 0% gradient significantly increased gross margin for rice, wheat and the total RW system. As for the RW system, levelling to 0% with a flat configuration significantly increased WPi of both crops in the MW system compared to FL, but by a lesser proportion. Raised beds significantly increased yield of maize by 8% (0.5 t ha-1), reduced irrigation amount by 20% (40 mm) and increased WPi by 34% (1.0 kg m-3) in comparison with the laser levelled flat plots. Gross margin of the MW system on beds was 17-20% higher than FL, and gross margin with beds on a 0.1% gradient was significantly higher than either gradient on the flat. The results suggest that the gains from levelling with a 0.1% gradient compared to 0% are marginal; however, this may change if the goal of consolidation of small farmer plots into larger fields becomes a reality provided there is a proportionate increase in irrigation flow rates, and ability to drain.

Response and resilience of Asian agrifood systems to COVID-19: An assessment across twenty-five countries and four regional farming and food systems.

Context: The COVID-19 pandemic has been affecting health and economies across the world, although the nature of direct and indirect effects on Asian agrifood systems and food security has not yet been well understood. Objectives: This paper assesses the initial responses of major farming and food systems to COVID-19 in 25 Asian countries, and considers the implications for resilience, food and nutrition security and recovery policies by the governments. Methods: A conceptual systems model was specified including key pathways linking the direct and indirect effects of COVID-19 to the resilience and performance of the four principal Asian farming and food systems, viz, lowland rice based; irrigated wheat based; hill mixed; and dryland mixed systems. Based on this framework, a systematic survey of 2504 key informants (4% policy makers, 6% researchers or University staff, 6% extension workers, 65% farmers, and 19% others) in 20 Asian countries was conducted and the results assessed and analysed. Results and conclusion: The principal Asian farming and food systems were moderately resilient to COVID-19, reinforced by government policies in many countries that prioritized food availability and affordability. Rural livelihoods and food security were affected primarily because of disruptions to local labour markets (especially for off-farm work), farm produce markets (notably for perishable foods) and input supply chains (i.e., seeds and fertilisers). The overall effects on system performance were most severe in the irrigated wheat based system and least severe in the hill mixed system, associated in the latter case with greater resilience and diversification and less dependence on external inputs and long market chains. Farming and food systems' resilience and sustainability are critical considerations for recovery policies and programmes, especially in relation to economic performance that initially recovered more slowly than productivity, natural resources status and social capital. Overall, the resilience of Asian farming and food systems was strong because of inherent systems characteristics reinforced by public policies that prioritized staple food production and distribution as well as complementary welfare programmes. With the substantial risks to plant- and animal-sourced food supplies from future zoonoses and the institutional vulnerabilities revealed by COVID-19, efforts to improve resilience should be central to recovery programmes. Significance: This study was the first Asia-wide systems assessment of the effects of COVID-19 on agriculture and food systems, differentiating the effects of the pandemic across the four principal regional farming and food systems in the region.

Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood.

Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) mainly in young adults, and a breakage of immune tolerance to CNS self-antigens has been suggested to initiate CNS autoimmunity. Age and microbial infection are well-known factors involved in the development of autoimmune diseases, including MS. Recent studies have suggested that alterations in the gut microbiota, referred to as dysbiosis, are associated with MS. However, it is still largely unknown how gut dysbiosis affects the onset and progression of CNS autoimmunity. In this study, we investigated the effects of age and gut dysbiosis on the development of CNS autoimmunity in humanized transgenic mice expressing the MS-associated MHC class II (MHC-II) gene, HLA-DR2a, and T-cell receptor (TCR) genes specific for MBP87-99/DR2a that were derived from an MS patient. We show here that the induction of gut dysbiosis triggers the development of spontaneous experimental autoimmune encephalomyelitis (EAE) during adolescence and early young adulthood, while an increase in immunological tolerance with aging suppresses disease onset after late young adulthood in mice. Furthermore, gut dysbiosis induces the expression of complement C3 and production of the anaphylatoxin C3a, and down-regulates the expression of the Foxp3 gene and anergy-related E3 ubiquitin ligase genes. Consequently, gut dysbiosis was able to trigger the development of encephalitogenic T cells and promote the induction of EAE during the age window of young adulthood.

Double Dehydrogenation of Primary Amines to Nitriles by a Ruthenium Complex Featuring Pyrazole Functionality.

A ruthenium(II) complex bearing a naphthyridine-functionalized pyrazole ligand catalyzes oxidant-free and acceptorless selective double dehydrogenation of primary amines to nitriles at moderate temperature. The role of the proton-responsive entity on the ligand scaffold is demonstrated by control experiments, including the use of a N-methylated pyrazole analogue. DFT calculations reveal intricate hydride and proton transfers to achieve the overall elimination of 2 equiv of H2.

dl-trans-3,4-Dihydroxy-1-selenolane (DHSred) heals indomethacin-mediated gastric ulcer in mice by modulating arginine metabolism.

BACKGROUND: The importance of the arginine metabolism in gastric ulcer-healing is given relatively less attention. Hence the role of controlling this pathway by dl-trans-3,4-dihydroxy-1-selenolane (DHSred) and omeprazole against indomethacin-induced stomach ulceration in mouse was investigated. METHODS: Swiss albino mice were ulcerated with indomethacin followed by treatment with the test samples, and the activities of myeloperoxidase (MPO), total nitric oxide synthase (NOS) and arginase, the expressions of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS), and the pro-/anti-inflammatory cytokine levels were assayed. NOS-inhibitors were also used to establish the biochemical mechanism. RESULTS: Indomethacin induced maximum ulceration in mice on the 3rd day, associated with reduced arginase activity, eNOS expression, along with increased MPO and total NOS activities, nitric oxide (NO) generation, iNOS expression, and pro-/anti-inflammatory (Th1/Th2) cytokine ratio. Treatment with DHSred (2.5mgkg(-1)×3days) restored the cytokine balance to shift the iNOS/NO axis to the arginase/polyamine axis as revealed from the increased arginase activity and eNOS expression, and reduced iNOS expression, total NOS activity and NO level. CONCLUSIONS: The ulcer-healing property of DHSred, but not of omeprazole was due to a favorable pro-/anti-inflammatory cytokine ratio that shifted the arginine metabolism to the polyamine pathway and increased the eNOS/iNOS ratio. The healing action of omeprazole was not significantly associated with these parameters. GENERAL SIGNIFICANCE: The shift in the ariginine-metabolism from the iNOS/NO axis to the arginase/polyamine axis is guided by Th1/Th2 cytokines ratio and plays an important role in gastric ulcer-healing. The favourable effects of the non-toxic and water-soluble compound, DHSred on these pathways and other COX-dependent and antioxidative parameters suggested it to be a promising anti-ulcer formulation for further studies.

Advances in the immunopathogenesis of multiple sclerosis.

PURPOSE OF REVIEW: Recent studies indicate a role for immune dysregulation in the pathogenesis of multiple sclerosis, an inflammatory demyelinating and degenerative disease of the central nervous system. This review addresses the current mechanisms of immune dysregulation in the development of multiple sclerosis, including the impact of environmental risk factors on immunity in both multiple sclerosis and its animal models. RECENT FINDINGS: CD4 T-helper (Th) cells have long been implicated as the main drivers of pathogenesis of multiple sclerosis. However, current studies indicate that multiple sclerosis is largely a heterogeneous disease process, which involves both innate and adaptive immune-mediated inflammatory mechanisms that ultimately contribute to demyelination and neurodegeneration. Therefore, B cells, CD8 T cells, and microglia/macrophages can also play an important role in the immunopathogenesis of multiple sclerosis apart from proinflammatory CD4 Th1/Th17 cell subsets. Furthermore, increasing evidence indicates that environmental risk factors, such as Vitamin D deficiency, Epstein-Barr virus, smoking, Western diet, and the commensal microbiota, influence the development of multiple sclerosis through interactions with genetic variants of multiple sclerosis, thus leading to the dysregulation of immune responses. SUMMARY: A better understanding of immune-mediated mechanisms in the pathogenesis of multiple sclerosis and the contribution of environmental risk factors toward the development of multiple sclerosis will help further improve therapeutic approaches to prevent disease progression.

Inhibition of TNF-α, and NF-κB and JNK pathways accounts for the prophylactic action of the natural phenolic, allylpyrocatechol against indomethacin gastropathy.

BACKGROUND: The gastro-intestinal disorders, induced by the NSAIDs including indomethacin (IND) remain unresolved medical problems. Herein, we disclose allylpyrocatechol (APC) as a potential agent against IND-gastropathy and rationalize its action mechanistically. METHODS: Mice were pre-treated with APC for 1h followed by IND (18mgkg(-1)) administration, and the ulcer-prevention capacity of APC was evaluated on the 3rd day by histology. Its effect on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COX, prostaglandins, growth factors and their receptors) and signaling parameters (NF-κB and MAPKs) were assessed by immunoblots/mRNA, and ELISA at the time points of their maximal changes due to IND administration. RESULTS: IND induced oxidative stress, triggering mucosal TNF-α that activated NF-κB and JNK MAPK signaling in mice. These increased the pro-inflammatory biochemical parameters, but reduced the healing factors. APC reversed all the adverse effects to prevent gastric ulceration. APC (5mgkg(-1)), trolox (50mgkg(-1)) and NAC (250mgkg(-1)) showed similar protection that was better than that by misoprostol (5µgkg(-1)) and omeprazole (3mgkg(-1)). CONCLUSIONS: The anti-ulcer effect of APC can be primarily attributed to its antioxidant action that helped in controlling various inflammatory parameters and augmenting angiogenesis. GENERAL SIGNIFICANCE: Given that APC is an effective, non-toxic antioxidant with appreciable natural abundance, further evaluation of its pharmacokinetics and dynamics would help in promoting it as a new anti-inflammatory agent.

In vitro and in vivo evaluation of tannic acid as an antibacterial agent in broilers infected with Salmonella Typhimurium.

This study was conducted to evaluate tannic acid (TA) as an antibacterial agent against Salmonella Typhimurium in in vitro and in vivo chicken models. The TA formed an inhibitory zone against Salmonella enterica serotypes including S. Typhimurium, S. Enteritidis, and S. Infantis. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of TA against Salmonella Typhimurium nalidixic acid resistant strain (STNR) were determined as 40 and 700 µg/mL, respectively. Sublethal doses of TA (5, 10, and 20 µg/mL) restricted swimming and swarming motility and biofilm formation of STNR compared to the control group (0 µg/mL) (P < 0.05). The TA-bovine serum albumin (BSA) complex formed at simulated gastric pH (pH 3.75) was hydrolyzed at pH 6.75 and 7.25 (P < 0.05), and the hydrolysis of the TA-BSA complex was stronger at pH 7.25 compared to the pH 6.75 (P < 0.05). The inhibitory zone of the TA-BSA complex against STNR at pH 6.75 was lower than TA without BSA at 30 and 60 min (P < 0.05), but not at 120 min (P > 0.1). The inhibitory zone of the TA-BSA complex against STNR at pH 7.25 was not decreased at 0, 30, and 60 min compared to TA without BSA (P > 0.1). The recovery rate of TA was 83, 54.8, 10.5, and 19.6% in the gizzard, jejunum, ileum, and ceca, respectively, in broiler chickens. The STNR-infected broilers fed 0.25 g/kg of TA had significantly lower unweighted beta diversity distance compared to the sham-challenged control (SCC) and challenged controlled (CC) group on D 21. TA supplementation linearly (P < 0.05) and quadratically (tendency; P = 0.071) reduced relative abundance of the family Peptostreptococcaceae in broilers infected with STNR on D 7. TA supplementation linearly (P < 0.05) and quadratically (tendency; P = 0.06) increased the relative abundance of the family Erysipelotrichaceae in broilers infected with STNR on D 21. Therefore, TA has potential to be used as an antibacterial agent against the S. Typhimurium infection in broilers.

Effects of levels of methionine supplementations in forms of L- or DL-methionine on the performance, intestinal development, immune response, and antioxidant system in broilers challenged with Eimeria spp.

The study was conducted to investigate the effects of 2 isoforms of methionine on growth performance and intestinal health induced by methionine (Met) deficiency and Eimeria infection in broilers. A total of 720 one-day old male chicks (Cobb500) were randomly allocated to 10 groups in a 2 × 5 factorial arrangement (6 reps/group, 12 birds/cage) with diets and Eimeria challenge as the main factors. Hundred percent DL-Met, 100% L-Met, 80% DL-Met, and 80% L-Met diets were formulated to meet approximately 100 or 80% of the total sulfur amino acid (TSAA) requirement with DL-Met or L-Met as Met supplementation sources. The 60% TSAA basal diet (60% Met) was formulated without Met supplementation. At d14, the challenge groups were gavaged with mixed Eimeria spp. Growth performance was recorded on d7, 14, 20 (6-day postinfection [DPI]), and 26 (12 DPI). The gut permeability was measured on 5 and 11 DPI. Antioxidant status and gene expression of immune cytokines and tight junction proteins were measured on 6 and 12 DPI. Data were analyzed by 1-way and 2-way ANOVA before and after the challenge, respectively. Orthogonal polynomial contrasts were used for post hoc comparison. Overall, the Eimeria challenge and 60% Met diet significantly reduced growth performance, antioxidant status, and mRNA expression of tight junction genes and immune cytokines. For other Met treatments, the L-Met groups had significantly higher BWG and lower FCR than the DL-Met group from d 1 to 20. The L-Met groups had less gut permeability than the DL-Met groups on 5 DPI. Compared to the 80% Met groups, the 100% Met groups reduced gut permeability. At 6 DPI, the 80% Met groups showed higher ZO1 expression than the 100% Met groups. The challenge groups had higher Muc2 expression and GSH/GSSG compared to the nonchallenge groups, and SOD activity was lower in the L-Met groups compared to the DL-Met groups at 6 DPI. The 100% Met groups had higher GPx activity than the 80% Met groups at 12 DPI. In conclusion, during coccidiosis, the 100% Met groups had better gut integrity and antioxidant status. Met supplementation in the form of L-Met improved growth performance in the starter phase and gut permeability in the challenge phase.

Nutrient profile and effects of carinata meal as alternative feed ingredient on broiler performance, tight junction gene expression and intestinal morphology.

Two studies were conducted to establish carinata meal as a partial replacement of conventional protein sources. Study I was conducted to determine the nutrient profile, nitrogen-corrected true metabolizable energy (TMEn), and amino acid (AA) digestibility of 2 groups: low glucosinolate carinata meal (LGCM) and high glucosinolate carinata meal (HGCM) using rooster assays. The LGCM contained 28 µmol/g glucosinolate, 11.5% moisture, 39.2% crude protein (CP), whereas the HGCM had 100 µmol/g glucosinolate, 10.1% moisture, 39.5% CP on as is basis. The precision-fed rooster assays were conducted to determine TMEn and AA digestibility. The TMEn levels of LGCM and HGCM were 1,814 and 1,690 kcal/kg on as is basis, respectively. Standardized digestibility for lysine, methionine, cysteine, threonine, and valine were 72, 88, 69, 75, and 79% for LGCM and 80, 89, 71, 76, and 80% for HGCM, respectively. Based on the nutrient profiles from study I, study II was conducted to evaluate the effects of LGCM and HGCM in broilers. A total of 504 one-day-old Cobb500 male broiler chickens were randomly divided into 42 battery cages with 6 replicates of 12 birds per cage. The seven dietary treatments were control diet, 3 inclusion levels of LGCM (4, 8, and 12%), and 3 of HGCM (4, 8, and12%) in a corn-SBM based diet fed for 21 d. No significant differences in BW, BWG, and FI were observed except for significantly lower BWG in 12% HGCM group compared to control for 14-21 days (P < 0.05). The FCR for 12% HGCM increased significantly compared to 4 and 8% of both LGCM and HGCM groups during wk 3 (14-21 d). Based on these studies, carinata meal could be recommended to partially replace conventional feed ingredients at a rate of 12% when LGCM is used and 8% when HGCM is used with no deleterious effects on growth performance, gut histology, and tight junction proteins.

Effects of supplemental tannic acid on growth performance, gut health, microbiota, and fat accumulation and optimal dosages of tannic acid in broilers.

This study was conducted to investigate the effects of different dosages of tannic acid (TA) on growth performance, nutrient digestibility, gut health, immune system, oxidative status, microbial composition, volatile fatty acids (VFA), bone mineral density, and fat digestion and accumulation in broilers and to find optimal dosages of TA for efficient growth and gut health in broilers. A total of 320 male Cobb500 broilers were randomly distributed to 4 treatments with 8 replicates including 1) tannic acid 0 (TA0): basal diet without TA; 2) tannic acid 0.5 (TA0.5): basal diet with 0.5 g/kg TA; 3) tannic acid 1.5 (TA1.5); and 4) tannic acid 2.5 (TA2.5). Supplemental TA at levels greater than 972 mg/kg tended to reduce BW on D 21 (p = 0.05). The TA2.5 had significantly lower apparent ileal digestibility (AID) of crude protein compared to the TA0 group. The AID of ether extract tended to be reduced by TA at levels greater than 525 mg/kg (p = 0.08). The jejunal lipase activities tended to be reduced by TA at levels less than 595.3 mg/kg (p = 0.09). TA linearly decreased goblet cell density in the crypts of the jejunum (p < 0.05) and reduced mRNA expression of mucin two at levels less than 784.9 mg/kg and zonula occludens two at levels less than 892.6 mg/kg (p < 0.05). The TA0.5 group had higher activities of liver superoxide dismutase compared to the TA0 group (p < 0.05). Bone mineral density and contents tended to be linearly decreased by TA (p = 0.05), and the ratio of lean to fat was linearly decreased (p < 0.01). Total cecal VFA production tended to be linearly reduced by TA at levels greater than 850.9 mg/kg (p = 0.07). Supplemental TA tended to increase the relative abundance of the phylum Bacteroidetes (p = 0.1) and decrease the relative abundance of the phylum Proteobacteria (p = 0.1). The relative abundance of the family Rikenellaceae was the lowest at 500 mg/kg TA, and the relative abundance of the family Bacillaceae was the highest at 1,045 mg/kg TA. Collectively, these results indicate that the optimum level of supplemental TA would range between 500 and 900 mg/kg; this range of TA supplementation would improve gut health without negatively affecting growth performance in broilers under antibiotic-free conditions.

Assessing Potential Environmental Impacts of Pesticide Usage in Paddy Ecosystems: A Case Study in the Deduru Oya River Basin, Sri Lanka.

Rice paddies are unique ecosystems that provide rich wetland habitat. Their enduring existence across vast stretches of land has led them to evolve into unique systems serving a diverse assemblage of organisms and sustaining a staple grain for many people. With food demand rising, agricultural intensification through agrochemical application is a common practice used to boost food production in developing countries, including Sri Lanka. The aim of the present study was to assess the concentration of pesticide residues in water in rice ecosystems and discover their potential impacts on both environmental health and the most common fauna groups across a cropping year in Sri Lanka. A total of 270 water samples from waters associated with paddy fields within a watershed were analyzed for 20 commonly used pesticides; in addition, local farm holders were surveyed to assess pesticide usage details in three selected paddy tracts. We then used the Cornell University environmental impact quotient (EIQ) calculator and the ECOTOX Knowledgebase to determine the exposure risk associated with individual pesticides relative to their application rates and aquatic concentrations. Survey results demonstrate that several pesticides were overapplied at rates 1.2-11 times the recommended application, and the EIQ demonstrated high environmental risk of two of the agrochemicals detected, 2-methyl-4-chlorophenoxyacetic and diazinon. Fish, amphibians, insects, and beetles were found to have a wide range of potential adverse outcomes from exposure to diazinon, captan, thiamethoxam, and chlorantraniliprole. To balance the trade-offs between food security and ecosystem sustainability, the present study recommends that adoption of quantifiable environmental health indicators be considered as part of the national policy regulating pesticide use. Environ Toxicol Chem 2022;41:343-355. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Fecal Lcn-2 level is a sensitive biological indicator for gut dysbiosis and intestinal inflammation in multiple sclerosis.

Multiple Sclerosis (MS) has been reported to be associated with intestinal inflammation and gut dysbiosis. To elucidate the underlying biology of MS-linked gut inflammation, we investigated gut infiltration of immune cells during the development of spontaneous experimental autoimmune encephalomyelitis (EAE) in humanized transgenic (Tg) mice expressing HLA-DR2a and human T cell receptor (TCR) specific for myelin basic protein peptide (MBP87-99)/HLA-DR2a complexes. Strikingly, we noted the simultaneous development of EAE and colitis, suggesting a link between autoimmune diseases of the central nervous system (CNS) and intestinal inflammation. Examination of the colon in these mice revealed the infiltration of MBP-specific Th17 cells as well as recruitment of neutrophils. Furthermore, we observed that fecal Lipocalin-2 (Lcn-2), a biomarker of intestinal inflammation, was significantly elevated and predominantly produced by the gut-infiltrating neutrophils. We then extended our findings to MS patients and demonstrate that their fecal Lcn-2 levels are significantly elevated compared to healthy donors (HDs). The elevation of fecal Lcn-2 levels correlated with reduced bacterial diversity and increased levels of other intestinal inflammation markers including neutrophil elastase and calprotectin. Of interest, bacteria thought to be beneficial for inflammatory bowel disease (IBD) such as Anaerobutyricum, Blautia, and Roseburia, were reduced in fecal Lcn-2-high MS patients. We also observed a decreasing trend in serum acetate (a short-chain fatty acid) levels in MS Lcn-2-high patients compared to HDs. Furthermore, a decrease in the relative abundance of Blautia massiliensis was significantly associated with a reduction of acetate in the serum of MS patients. This study suggests that gut infiltration of Th17 cells and recruitment of neutrophils are associated with the development of gut dysbiosis and intestinal inflammation, and that fecal Lcn-2 level is a sensitive biological indicator for gut dysbiosis in multiple sclerosis.

Black tea and theaflavins assist healing of indomethacin-induced gastric ulceration in mice by antioxidative action.

The healing activities of black tea (BT) and the theaflavins (TF) against the indomethacin-induced stomach ulceration were studied in a mouse model. Indomethacin (18 mg/kg, p.o.) administration induced maximum ulceration in the glandular portion of the gastric mucosa on the 3rd day, accompanied by increased lipid peroxidation and protein oxidation, depletion of thiol-defense and mucin, as well as reduced expressions of cyclooxygenases (COX) and prostaglandin (PG) E synthesis in the gastric tissues, and plasma total antioxidant status of mice. Treatment with BT (40 mg/kg), TF (1 mg/kg), and omeprazole (3 mg/kg) produced similar (74%-76%) ulcer healing, as revealed from the histopathological studies. Treatment with all the above samples reversed the adverse oxidative effects of indomethacin significantly. BT and TF also enhanced the PGE synthesis by augmenting the expressions of COX 1 and 2, but did not modulate acid secretion.

Evaluating endogenous loss and standard ileal digestibility of amino acids in response to the graded severity levels of E. maxima infection.

The study was conducted to evaluate the effects of graded levels of Eimeria maxima challenge on endogenous loss, apparent ileal digestibility (AID), and standard ileal digestibility (SID) of amino acids. A total of 768 fourteen-day-old male Cobb 500 broiler chickens were randomly allocated into 64 battery cages. Apart from the regular corn-soybean based diet, the nitrogen-free diet (NFD) was formulated to determine the endogenous loss of amino acids. One-half of the birds (32 cages) were fed the NFD, and another half fed the regular diet from d 14 to 20. Both groups were further assigned to 4 treatments (nonchallenged control or three levels of challenge doses) with 8 replicate cages. The challenge doses were: the low challenge dose (Low) with E. maxima 12,500 oocysts, the medium challenge dose (Medium) with 25,000 E. maxima oocysts, and the high challenge dose (High) with 50,000 E. maxima oocysts. At 6 d postinfection, ileal digesta samples were collected and the intestinal lesion score were recorded. The results indicated a significant linear increase of endogenous amino acid flow in response to the graded E. maxima challenge. Moreover, the AID and SID of amino acids were linearly reduced due to the increasing challenge dose. The study demonstrated that NFD significantly reduced lesion scores, underestimating the true endogenous losses of birds fed regular diets. Even though the endogenous loss of amino acids was underestimated, they were linearly increased in response to the graded E. maxima challenge. In conclusion, the higher Eimeria dose birds were challenged with, the more endogenous amino acids were released into the intestine and the lower dietary nutrients were digested and absorbed by broiler chickens.

Effects of low-crude protein diets supplemented with arginine, glutamine, threonine, and methionine on regulating nutrient absorption, intestinal health, and growth performance of Eimeria-infected chickens.

The study was conducted to evaluate the effects of low crude protein diets supplemented with arginine, glutamine, methionine, and/or threonine on apparent ileal digestibility of amino acids, intestinal morphology, intestinal permeability, gene expression of nutrient transporters, and tight junction proteins of broiler chickens challenged with mixed Eimeria spp. A total of five hundred seventy-six, 12-day-old male broiler chickens were allocated into 8 treatments, and 6 replicate cages of 12 chickens per cage. This experiment included a nonchallenged control (NC) fed regular corn-soybean meal-based diet (Regular diet, 19% crude protein), an Eimeria-challenged control (CC) fed Regular diet, an Eimeria challenge group fed low-crude protein diet (LCP, 16% crude protein), 4 Eimeria challenge groups fed low-crude protein diet supplemented with 0.75% arginine, glutamine, methionine, and threonine, respectively (ARG, GLN, MET, and THR), and an Eimeria challenge group fed low-crude protein diet with 0.75% supplemented arginine, glutamine, methionine, and threonine collectively as a combination group (COMB). On d 14, birds in the challenge groups were gavaged with a mixed Eimeria spp. solution containing 12,500 oocysts of E. maxima, 12,500 oocysts of E. tenella, and 62,500 oocysts of E. acervulina. The results showed that the Eimeria challenge reduced overall growth performance, but the LCP had no adverse impacts on intestinal health and growth of Eimeria-infected birds compared to the CC. Additionally, supplementation of crystalline arginine, glutamine, methionine, and threonine improved the apparent ileal digestibility of these specific amino acids on 6 dpi. Moreover, the THR treatment increased villus height in the duodenum. The ARG treatment decreased intestinal permeability and gene expression of amino acid transporters, whereas the GLN and THR treatments both reversed adverse effects of coccidiosis on gene expression of tight junction protein (claudin 1). However, the MET and COMB treatments exacerbated infection severity of coccidiosis. In summary, adding 0.75% of arginine, glutamine, or threonine in a low crude protein diet can improve the intestinal health of birds challenged with a mild coccidia infection.

Effect of switching glatiramer acetate formulation from 20 mg daily to 40 mg three times weekly on immune function in multiple sclerosis.

BACKGROUND: Many RRMS patients who had been treated for over 20 years with GA 20 mg/ml daily (GA20) switched to 40 mg/ml three times-a-week (GA40) to reduce injection-related adverse events. Although GA40 is as effective as GA20 in reducing annualized relapse rate and MRI activity, it remains unknown how switching to GA40 from GA20 affects the development of pathogenic and regulatory immune cells. OBJECTIVE: To investigate the difference in immunological parameters in response to GA20 and GA40 treatments. METHODS: We analyzed five pro-inflammatory cytokines (IL-1ß, IL-23, IL-12, IL-18, TNF-α), and three anti-inflammatory/regulatory cytokines (IL-10, IL-13, and IL-27) in serum. In addition, we analyzed six cytokines (IFN-γ, IL-17A, GM-CSF, IL-10, IL-6, and IL-27) in cultured PBMC supernatants. The development of Th1, Th17, Foxp3 Tregs, M1-like, and M2-like macrophages were examined by flow cytometry. Samples were analyzed before and 12 months post switching to GA40 or GA20. RESULTS: Pro- and anti-inflammatory cytokines were comparable between the GA40 and GA20 groups. Development of Th1, Th17, M1-like macrophages, M2-like macrophages, and Foxp3 Tregs was also comparable between the two groups. CONCLUSIONS: The immunological parameters measured in RRMS patients treated with GA40 three times weekly are largely comparable to those given daily GA20 treatment.