Host Physiological Responses Research Articles

Striking differences in virulence, transmission and sporocyst growth dynamics between two schistosome populations

BackgroundParasite traits associated with transmission success, such as the number of infective stages released from the host, are expected to be optimized by natural selection. However, in the trematode parasite Schistosoma mansoni, a key transmission trait, i.e. the number of cercariae larvae shed from infected Biomphalaria spp. snails, varies significantly within and between different parasite populations and selection experiments demonstrate that this variation has a strong genetic basis. In this study, we compared the transmission strategies of two laboratory schistosome population and their consequences for their snail host.MethodsWe infected inbred Biomphalaria glabrata snails using two S. mansoni parasite populations (SmBRE and SmLE), both isolated from Brazil and maintained in the laboratory for decades. We compared life history traits of these two parasite populations by quantifying sporocyst growth within infected snails (assayed using qPCR), output of cercaria larvae and impact on snail host physiological response (i.e. hemoglobin rate, laccase-like activity) and survival.ResultsWe identified striking differences in virulence and transmission between the two studied parasite populations. SmBRE (low shedder (LS) parasite population) sheds very low numbers of cercariae and causes minimal impact on the snail physiological response (i.e. laccase-like activity, hemoglobin rate and snail survival). In contrast, SmLE (high shedder (HS) parasite population) sheds 8-fold more cercariae (mean ± SE cercariae per shedding: 284 ± 19 vs 2352 ± 113), causes high snail mortality and has strong impact on snail physiology. We found that HS sporocysts grow more rapidly inside the snail host, comprising up to 60% of cells within infected snails, compared to LS sporocysts, which comprised up to 31%. Cercarial production is strongly correlated to the number of S. mansoni sporocyst cells present within the snail host tissue, although the proportion of sporocyst cells alone does not explain the low cercarial shedding of SmBRE.ConclusionsWe demonstrated the existence of alternative transmission strategies in the S. mansoni parasite consistent with trade-offs between parasite transmission and host survival: a “boom-bust” strategy characterized by high virulence, high transmission and short duration infections and a “slow and steady” strategy with low virulence, low transmission but long duration of snail host infections.

Duodenal Chemosensing of Short-Chain Fatty Acids: Implications for GI Diseases.

Short-chain fatty acids (SCFAs), the main bacterial fermentation products in the hindgut of hindgut fermenters, are also present in the foregut lumen. We discuss the impact of SCFAs in the duodenal defense mechanisms and in the gastrointestinal (GI) pathogenesis. Luminal SCFAs augment the duodenal mucosal defenses via release of serotonin (5-HT) and glucagon-like peptide-2 (GLP-2) from enteroendocrine cells. Released GLP-2 protects the small intestinal mucosa from nonsteroidal anti-inflammatory drug-induced enteropathy. SCFAs are also rapidly absorbed via SCFA transporters and interact with afferent and myenteric nerves. Excessive SCFA signals with 5-HT3 receptor overactivation may be implicated in the pathogenesis of irritable bowel syndrome symptoms. SCFA production exhibits diurnal rhythms with host physiological responses, suggesting that oral SCFA treatment may adjust the GI clocks. SCFAs are not only a source of energy but also signaling molecules for the local regulation of the GI tract and systemic regulation via release of gut hormones. Targeting SCFA signals may be a novel therapeutic for GI diseases and metabolic syndrome.

Immunity, immunomodulation, and antibiotic alternatives to maximize the genetic potential of poultry for growth and disease response

Multiple challenges confront the increasing demand for wholesome poultry food products, including governmental restrictions on the use of antibiotic growth promoters (AGPs), nutritional requirements to obtain maximum growth potential, understanding crosstalks among the immunity–microbiota–neuroendocrine system in the gut to maximize intestinal efficiency, high-density production conditions, waste management, and the emergence of infectious pathogens, particularly those that emerge in the antibiotic-free animal production environment. Although in-feed antibiotics have dramatically increased the efficiency of commercial poultry production over the last 50 years, we are now faced with an increasing global crisis concerning the heightened use of antibiotics in animal agriculture and the emergence of multidrug-resistant superbugs that threaten disease management in animals and humans. Therefore, much interest has focused on the development of alternative, antibiotic-free methods of commercial poultry production. Initially, alternatives to antibiotics included any strategies that replace AGPs, but now include any feed additives or treatment that will allow antibiotic-free animal production to prevent and/or treat diseases. These newer disease control strategies can be classified broadly into those that are directly cytotoxic against infectious agents or remove pathogenic toxins, including vaccines, hyperimmune antibodies, antimicrobial peptides, and bacteriophages, and those that augment non-specific host immunity and gut health, including phytochemicals, adjuvants, prebiotics, and probiotics. Furthermore, because the gut microbiota influences various physiological aspects of the immune response, brain function, and gut health, most antibiotic alternatives are expected to promote beneficial microbes that will benefit host physiological responses. However, there is a timely need to better understand the role of the microbiota in gut health if we want to use microbes to modulate the host response to enhance growth performance. This review will highlight current knowledge of host immunity in poultry, and various strategies to modulate host immunity, growth performance, and disease responses to guide the development of alternatives to reduce the use of antibiotics, using a few selected alternatives and a description of their efficacy and modes of action.

Antimicrobial promotion of pig growth is associated with tissue-specific remodeling of bile acid signature and signaling

The spread of bacterial resistance to antimicrobials (AMA) have intensified efforts to discontinue the non-therapeutic use of AMA in animal production. Finding alternatives to AMA, however, is currently encumbered by the obscure mechanism that underlies their growth-promoting action. In this report, we demonstrate that combinations of antibiotics and zinc oxide at doses commonly used for stimulating growth or preventing post-weaning enteritis in pigs converge in promoting microbial production of bile acids (BA) in the intestine. This leads to tissue-specific modifications in the proportion of BA, thereby amplifying BA signaling in intestine, liver, and white adipose tissue (WAT). Activation of BA-regulated pathways ultimately reinforces the intestinal protection against bacterial infection and pathological secretion of fluids and electrolytes, attenuates inflammation in colon and WAT, alters protein and lipid metabolism in liver, and increases the circulating levels of the hormone FGF19. Conceivably, these alterations could spare nutrients for growth and improve the metabolic efficiency of AMA-treated animals. This work provides evidence that BA act as signaling molecules that mediate host physiological, metabolic, and immune responses to the AMA-induced alterations in gut microbial metabolism, eventually permitting the growth-promoting action of AMA. Consequently, BA emerge as a promising target for developing efficacious alternatives to AMA.

Comparative biogeography of the gut microbiome between Jinhua and Landrace pigs

The intestinal microbiome is critically important in shaping a variety of host physiological responses. However, it remains elusive on how gut microbiota impacts overall growth and more specifically, adipogenesis. Using the pig as an animal model, we compared the differences in bacterial community structure throughout the intestinal tract in two breeds (Landrace and Jinhua) of pigs with distinct phenotypes. The Landrace is a commercial purebred and the Jinhua is a Chinese indigenous, slow-growing breed with high propensity for fat deposition. Using 16S rRNA gene sequencing, we revealed that the bacterial communities are more diverse in the duodenum, jejunum, and cecum of Jinhua pigs than in those of Landrace pigs, whereas the ileal and colonic microbiota show a similar complexity between the two breeds. Furthermore, a number of bacterial taxa differentially exist in Jinhua and Landrace pigs throughout the entire intestinal tract, with the jejunal and ileal microbiome showing the greatest contrast. Functional prediction of the bacterial community suggested increased fatty acid biosynthesis in Jinghua pigs, which could partially explain their adiposity phenotype. Further studies are warranted to experimentally verify the relative contribution of each enriched bacterial species and their effect on adipogenesis and animal growth.

Impact of resistant vs. digested starch on starch energy value in the pig gut

A major energy substrate for monogastric species such as humans and swine is starch from cereal grains, pulses and tubers. The rate, site and extent of starch digestion in the gastro-intestinal tract are dependent on the intrinsic factors of starch origin and the extrinsic factors such as applied processing methods. In monogastric species, starch escaping small intestinal digestion becomes readily available for microbial fermentation in the hindgut and has been coined resistant starch (RS) accordingly. Host physiological and metabolic responses differ according to the site and rate of starch digestion; however, the quantity of energy derived to the host from fermented vs. digested starch remains debated. A detailed understanding of the underlying mechanisms that cause nutrient flow and substrate availability in the hindgut to alter host energy metabolism and growth potential is lacking. Dietary RS may in fact have nearly equal energetic efficiency as digested starch due adequate provision of short chain fatty acids (SCFAs) and decreased energy loss due to decreased activity. Thus, proper characterization of the energetic efficiency of purified and whole grain starch sources is required for accurate diet formulation. This review will focus on how various methodologies can be used to quantify site, extent and kinetics of starch digestion, illustrating the differences in energetic efficiency between RS vs. digested starch.

The Impact of Western Diet and Nutrients on the Microbiota and Immune Response at Mucosal Interfaces.

Recent findings point toward diet having a major impact on human health. Diets can either affect the gut microbiota resulting in alterations in the host’s physiological responses or by directly targeting the host response. The microbial community in the mammalian gut is a complex and dynamic system crucial for the development and maturation of both systemic and mucosal immune responses. Therefore, the complex interaction between available nutrients, the microbiota, and the immune system are central regulators in maintaining homeostasis and fighting against invading pathogens at mucosal sites. Westernized diet, defined as high dietary intake of saturated fats and sucrose and low intake of fiber, represent a growing health risk contributing to the increased occurrence of metabolic diseases, e.g., diabetes and obesity in countries adapting a westernized lifestyle. Inflammatory bowel diseases (IBD) and asthma are chronic mucosal inflammatory conditions of unknown etiology with increasing prevalence worldwide. These conditions have a multifactorial etiology including genetic factors, environmental factors, and dysregulated immune responses. Their increased prevalence cannot solely be attributed to genetic considerations implying that other factors such as diet can be a major contributor. Recent reports indicate that the gut microbiota and modifications thereof, due to a consumption of a diet high in saturated fats and low in fibers, can trigger factors regulating the development and/or progression of both conditions. While asthma is a disease of the airways, increasing evidence indicates a link between the gut and airways in disease development. Herein, we provide a comprehensive review on the impact of westernized diet and associated nutrients on immune cell responses and the microbiota and how these can influence the pathology of IBD and asthma.

The within-host dynamics of infection in trans-generationally primed flour beetles.

Many taxa exhibit plastic immune responses initiated after primary microbial exposure that provide increased protection against disease-induced mortality and the fitness costs of infection. In several arthropod species, this protection can even be passed from parents to offspring through a phenomenon called trans-generational immune priming. Here, we first demonstrate that trans-generational priming is a repeatable phenomenon in flour beetles (Tribolium castaneum) primed and infected with Bacillus thuringiensis (Bt). We then quantify the within-host dynamics of microbes and host physiological responses in infected offspring from primed and unprimed mothers by monitoring bacterial density and using mRNA-seq to profile host gene expression, respectively, over the acute infection period. We find that priming increases inducible resistance against Bt around a critical temporal juncture where host septicaemic trajectories, and consequently survival, may be determined in unprimed individuals. Our results identify a highly differentially expressed biomarker of priming, containing an EIF4-e domain, in uninfected individuals, as well as several other candidate genes. Moreover, the induction and decay dynamics of gene expression over time suggest a metabolic shift in primed individuals. The identified bacterial and gene expression dynamics are likely to influence patterns of bacterial fitness and disease transmission in natural populations.

Anopheline salivary protein genes and gene families: an evolutionary overview after the whole genome sequence of sixteen Anopheles species

BackgroundMosquito saliva is a complex cocktail whose pharmacological properties play an essential role in blood feeding by counteracting host physiological response to tissue injury. Moreover, vector borne pathogens are transmitted to vertebrates and exposed to their immune system in the context of mosquito saliva which, in virtue of its immunomodulatory properties, can modify the local environment at the feeding site and eventually affect pathogen transmission. In addition, the host antibody response to salivary proteins may be used to assess human exposure to mosquito vectors. Even though the role of quite a few mosquito salivary proteins has been clarified in the last decade, we still completely ignore the physiological role of many of them as well as the extent of their involvement in the complex interactions taking place between the mosquito vectors, the pathogens they transmit and the vertebrate host. The recent release of the genomes of 16 Anopheles species offered the opportunity to get insights into function and evolution of salivary protein families in anopheline mosquitoes.ResultsOrthologues of fifty three Anopheles gambiae salivary proteins were retrieved and annotated from 18 additional anopheline species belonging to the three subgenera Cellia, Anopheles, and Nyssorhynchus. Our analysis included 824 full-length salivary proteins from 24 different families and allowed the identification of 79 novel salivary genes and re-annotation of 379 wrong predictions. The comparative, structural and phylogenetic analyses yielded an unprecedented view of the anopheline salivary repertoires and of their evolution over 100 million years of anopheline radiation shedding light on mechanisms and evolutionary forces that contributed shaping the anopheline sialomes.ConclusionsWe provide here a comprehensive description, classification and evolutionary overview of the main anopheline salivary protein families and identify two novel candidate markers of human exposure to malaria vectors worldwide. This anopheline sialome catalogue, which is easily accessible as hyperlinked spreadsheet, is expected to be useful to the vector biology community and to improve the capacity to gain a deeper understanding of mosquito salivary proteins facilitating their possible exploitation for epidemiological and/or pathogen-vector-host interaction studies.

The microbiome and innate immunity.

The intestinal microbiome is a signalling hub that integrates environmental inputs, such as diet, with genetic and immune signals to affect the host's metabolism, immunity and response to infection. The haematopoietic and non-haematopoietic cells of the innate immune system are located strategically at the host-microbiome interface. These cells have the ability to sense microorganisms or their metabolic products and to translate the signals into host physiological responses and the regulation of microbial ecology. Aberrations in the communication between the innate immune system and the gut microbiota might contribute to complex diseases.

Effect of Bifidobacterium animalis subsp. lactis GCL2505 on the physiological function of intestine in a rat model.

Bifidobacterium animalis ssp. lactis GCL2505 has been shown to proliferate in the human intestine. The intestinal dynamics and physiological effects of GCL2505 as well as the mechanism underlying proliferation in the gut were investigated. GCL2505 showed markedly higher resistance to free bile acids (cholic and deoxycholic acids) than other bifidobacterial species. The intestinal dynamics of GCL2505 and B. longum ssp. longum JCM1217T was compared. The level of B. animalis ssp. lactis in the GCL2505‐administered group was remarkably higher than that of B. longum in the JCM1217T‐administered group. The distribution of B. animalis ssp. lactis through the intestine of the GCL2505‐administered group revealed that GCL2505 proliferated in the cecum. The physiological effects of GCL2505 and JCM 1217T were investigated. The cecal IgA level in the GCL2505‐administered group was significantly higher than that in the nontreated control group. In contrast, the JCM 1217T‐administered group did not manifest any change in the cecal IgA level. Mucin excretion in the GCL2505‐administered group was significantly higher than that in the JCM 1217T‐administered group. The thickness of the sulfomucin layer of the colon in the GCL2505‐administered group tended to be higher than that in the JCM 1217T‐administered group. In a loperamide‐induced constipation model, fecal excretion in the GCL2505‐administered group was significantly increased compared with that in the loperamide‐treated control group. Short‐chain fatty acid concentration in the GCL2505‐administered group was significantly higher than that in the loperamide‐treated control group. These results indicate that the level of proliferation of probiotics in the intestine correlates with the magnitude of host physiological responses, such as IgA production and mucin secretion, which possibly affect gastrointestinal functions such as bowel movement to counteract constipation. GCL2505 exhibits high tolerance to secondary bile acids, which partially explains its higher rate of proliferation in the large intestine.

Atlantic salmon physiological and immune response to amoebic gill disease and insight into the biology of the amoeba

Amoebic gill disease (AGD) is an emerging disease in North European Atlantic salmon (Salmo salar) aquaculture caused by the amoeba Paramoeba perurans. Non-optimal environmental conditions such as increasing water temperature may affect AGD progression. To understand the role of predisposing environmental conditions on the biology of the parasite and on the host physiological and immune response, different clonal cultures of P. perurans and AGD infected Atlantic salmon were exposed, respectively, in vitro and in vivo to two different temperatures, 10°C and 15°C. Outputs from the in vitro experiment are 1) an improved understanding of the impact of temperature on amoebae growth rate during conditions that potentially influence disease development and 2) characterisation of changes in bacterial communities at different temperatures for different clonal cultures. Negative binomial analysis in R (R software, version 3.0.1) showed significant differences in growth rate among clonal cultures over time. Moreover, for each clonal culture, the fraction of amoebae in suspension in seawater showed a higher increase over time at 10°C, whereas the fraction of amoebae attached to the malt yeast agar (MYA) showed a higher increase over time at 15°C. 16S MiSeq analysis was also performed to characterise the changes in bacterial communities present in the cultures at the two different temperatures of the in vitro experiment. The host physiological and immune response to AGD infection during predisposing seasonal weather conditions (summer period) is still not well understood. Atlantic salmon smolts were exposed in vivo to the same temperatures used for the in vitro experiment, 10°C and 15°C, and to an initial concentration of 5000 cells l of a clonal culture of P. perurans for 3 weeks. Analyses of cortisol, glucose, and lactate concentration in plasma samples, white blood cell (wbc) differential count in blood smears, and gene expression have been performed at different time points after the challenge. The present results from the temperature dependent AGD infection and in vitro P. perurans growth rate studies hint that increased AGD outbreaks during summer periods may not be solely due to increased thermal stress in fish but also to increased amoebae attachment at 15°C which cause an increased gill pathology.

Effect of O. porcinus Tick Salivary Gland Extract on the African Swine Fever Virus Infection in Domestic Pig

African swine fever is a haemorrhagic disease in pig production that can have disastrous financial consequences for farming. No vaccines are currently available and animal slaughtering or area zoning to restrict risk-related movements are the only effective measures to prevent the spread of the disease. Ornithodoros soft ticks are known to transmit the African swine fever virus (ASFV) to pigs in farms, following the natural epidemiologic cycle of the virus. Tick saliva has been shown to modulate the host physiological and immunological responses during feeding on skin, thus affecting viral infection. To better understand the interaction between soft tick, ASFV and pig at the bite location and the possible influence of tick saliva on pig infection by ASFV, salivary gland extract (SGE) of Ornithodoros porcinus, co-inoculated or not with ASFV, was used for intradermal auricular inoculation. Our results showed that, after the virus triggered the disease, pigs inoculated with virus and SGE presented greater hyperthermia than pigs inoculated with virus alone. The density of Langerhans cells was modulated at the tick bite or inoculation site, either through recruitment by ASFV or inhibition by SGE. Additionally, SGE and virus induced macrophage recruitment each. This effect was enhanced when they were co-inoculated. Finally, the co-inoculation of SGE and virus delayed the early local spread of virus to the first lymph node on the inoculation side. This study has shown that the effect of SGE was powerful enough to be quantified in pig both on the systemic and local immune response. We believe this model should be developed with infected tick and could improve knowledge of both tick vector competence and tick saliva immunomodulation.

Metabolic, immune, and gut microbial signals mount a systems response to Leishmania major infection.

Parasitic infections such as leishmaniasis induce a cascade of host physiological responses, including metabolic and immunological changes. Infection with Leishmania major parasites causes cutaneous leishmaniasis in humans, a neglected tropical disease that is difficult to manage. To understand the determinants of pathology, we studied L. major infection in two mouse models: the self-healing C57BL/6 strain and the nonhealing BALB/c strain. Metabolic profiling of urine, plasma, and feces via proton NMR spectroscopy was performed to discover parasite-specific imprints on global host metabolism. Plasma cytokine status and fecal microbiome were also characterized as additional metrics of the host response to infection. Results demonstrated differences in glucose and lipid metabolism, distinctive immunological phenotypes, and shifts in microbial composition between the two models. We present a novel approach to integrate such metrics using correlation network analyses, whereby self-healing mice demonstrated an orchestrated interaction between the biological measures shortly after infection. In contrast, the response observed in nonhealing mice was delayed and fragmented. Our study suggests that trans-system communication across host metabolism, the innate immune system, and gut microbiome is key for a successful host response to L. major and provides a new concept, potentially translatable to other diseases.

The endothelin system has a significant role in the pathogenesis and progression of Mycobacterium tuberculosis infection.

Tuberculosis (TB) remains a major global health problem, and although multiple studies have addressed the relationship between Mycobacterium tuberculosis and the host on an immunological level, few studies have addressed the impact of host physiological responses. Proteases produced by bacteria have been associated with important alterations in the host tissues, and a limited number of these enzymes have been characterized in mycobacterial species. M. tuberculosis produces a protease called Zmp1, which appears to be associated with virulence and has a putative action as an endothelin-converting enzyme. Endothelins are a family of vasoactive peptides, of which 3 distinct isoforms exist, and endothelin 1 (ET-1) is the most abundant and the best-characterized isoform. The aim of this work was to characterize the Zmp1 protease and evaluate its role in pathogenicity. Here, we have shown that M. tuberculosis produces and secretes an enzyme with ET-1 cleavage activity. These data demonstrate a possible role of Zmp1 for mycobacterium-host interactions and highlights its potential as a drug target. Moreover, the results suggest that endothelin pathways have a role in the pathogenesis of M. tuberculosis infections, and ETA or ETB receptor signaling can modulate the host response to the infection. We hypothesize that a balance between Zmp1 control of ET-1 levels and ETA/ETB signaling can allow M. tuberculosis adaptation and survival in the lung tissues.

Control of alternaria black spot in persimmon fruit by a mixture of gibberellin and benzyl adenine, and its mode of action

In Israel, alternaria black spot (ABS) disease, caused by Alternaria alternata, is the main postharvest factor that reduces quality and impairs storability of persimmon fruit Diospyros kaki cv. Triumph. The fungus infects the fruit in the orchard and remains quiescent until harvest, or renews its development just before harvest, following rain or high humidity; it then preferentially colonizes the stem-end of the fruit. Recent findings suggest the importance of ethylene and respiration during early fruit growth as factors influencing maturity, crack development, and occurrence of ABS in the stem end of the fruit. We tested the effects of the growth regulator Superlon, a mixture of gibberellin (GA4+7) and benzyl adenine (BA), applied at 40μgmL−1 once a month during three consecutive months, on fruit physiological responses during growth and on ABS occurrence during storage at 0°C. Superlon treatments during the early stages of fruit growth, i.e., starting 40 days after fruit set (daf), applied once monthly during three consecutive months, inhibited ethylene and CO2 production in the stem end. Treatments applied starting 100daf enhanced cell proliferation under the fruit cuticle. Regardless of application timing, Superlon delayed chlorophyll degradation, and reduced fruit cuticle cracking and ABS susceptibility during the late stages of fruit growth and during storage. Present results suggest that the phytohormone, acting as a modulator of host physiological responses that result in delayed fruit maturation, is a main factor in enhanced resistance to ABS at harvest and during storage.

Deposition of pathogenic Mycoplasma gallisepticum onto bird feeders: host pathology is more important than temperature-driven increases in food intake

Although ambient temperature has diverse effects on disease dynamics, few studies have examined how temperature alters pathogen transmission by changing host physiology or behaviour. Here, we test whether reducing ambient temperature alters host foraging, pathology and the potential for fomite transmission of the bacterial pathogen Mycoplasma gallisepticum (MG), which causes seasonal outbreaks of severe conjunctivitis in house finches (Haemorhous mexicanus). We housed finches at temperatures within or below the thermoneutral zone to manipulate food intake by altering energetic requirements of thermoregulation. We predicted that pathogen deposition on bird feeders would increase with temperature-driven increases in food intake and with conjunctival pathology. As expected, housing birds below the thermoneutral zone increased food consumption. Despite this difference, pathogen deposition on feeders did not vary across temperature treatments. However, pathogen deposition increased with conjunctival pathology, independently of temperature and pathogen load, suggesting that MG could enhance its transmission by increasing virulence. Our results suggest that in this system, host physiological responses are more important for transmission potential than temperature-dependent alterations in feeding. Understanding such behavioural and physiological contributions to disease transmission is critical to linking individual responses to climate with population-level disease dynamics.

The Emerging Relevance of the Gut Microbiome in Cardiometabolic Health

The Emerging Relevance of the Gut Microbiome in Cardiometabolic Health

Bowel Microbiota Moderate Host Physiological Responses to Dietary Konjac in Weanling Rats1–3

Diets rich in complex carbohydrates that resist digestion in the small bowel can alter large bowel ecology and microbiota biochemistry because the carbohydrates become substrates for bacterial growth and metabolism. Conventional or germ-free weanling rats were fed a control diet or diets containing 1.25, 2.5, or 5% konjac (KJ), a commonly used ingredient in Asian foods, for 28 d. In the absence of bowel microbiota, 5% KJ elicited a significant increase in colonic goblet cell numbers and increased expression of mast cell protease genes and of genes that were overrepresented in the KEGG pathway “Metabolism of xenobiotics by cytochrome P450” relative to the control diet. In contrast, feeding 5% KJ caused few changes in mucosal gene expression in conventional rats. Analysis of the colonic microbiota of conventional rats fed KJ showed modest increases in the proportions of Actinobacteria and Bacteroidetes relative to rats fed the control diet, with a concomitant reduction in Firmicutes, which included a 50% reduction in Lactobacillus abundance. Colonic concentrations of short-chain fatty acids and colonic crypt lengths were increased by feeding KJ. Goblet cell numbers were greater in conventional rats fed KJ relative to the control diet but were lower compared with germ-free animals. Serum metabolite profiles were different in germ-free and conventional rats. Metabolites that differed in concentration included several phospholipids, a bile acid metabolite, and an intermediate product of tryptophan metabolism. Overall, KJ in the diet was potentially damaging to the bowel mucosa and produced a protective response from the host. This response was reduced by the presence of the bowel microbiota, which therefore ameliorated potentially detrimental effects of dietary KJ.

Introduction: the unfolded protein response’s role in disease pathophysiology

Introduction: the unfolded protein response’s role in disease pathophysiology