Enteroblastic adenocarcinoma of the ampulla of Vater / Adenocarcinoma enteroblástico de la ampolla de Vater

Adenocarcinoma with enteroblastic differentiation is a rare histologic subtype of adenocarcinoma of the gastrointestinal tract that shows unique histologic and immunohistochemical features that resemble fetal intestinal epithelium. This histological subtype has been widely described in the stomach, where it most frequently appears, but, in other locations, it is misdiagnosed because of the poor experience in routine diagnostic setting. Here we present a case of an 87-year-old male with an adenocarcinoma of the ampulla of Vater with enteroblastic differentiation with a literature review of the cases described of this subtype in this location to date. The anatomical peculiarity of the ampulla, joined with the infrequent nature of this histological subtype, makes this case of great interest to aid to better characterize the biological behavior of these tumors. (AU)

El adenocarcinoma con diferenciación enteroblástica es un subtipo histológico poco frecuente de adenocarcinoma gastrointestinal que muestra características histológicas e inmunohistoquímicas únicas que se asemejan al epitelio intestinal fetal. Este subtipo histológico ha sido ampliamente descrito en el estómago, donde aparece con mayor frecuencia, pero en otras localizaciones es mal diagnosticado debido a la poca experiencia en el diagnóstico de rutina. Presentamos un caso de un varón de 87 años con adenocarcinoma de ampolla de Vater con diferenciación enteroblástica, junto a una revisión bibliográfica de los casos descritos de este subtipo en esta localización hasta el momento. La peculiaridad anatómica de la ampolla, sumada al carácter poco frecuente de este subtipo histológico, dotan a este caso de gran interés para ayudar a caracterizar mejor el comportamiento biológico de estos tumores. (AU)

Gut dopamine kick: How gut microbes turn on host receptors to fight pathogens.

Common nutrients in our diet often affect our health through unexpected mechanisms. In a recent issue of Nature, Scott et al. show gut microbes convert dietary tryptophan into metabolites activating intestinal dopamine receptors, which can block attachment of bacterial pathogens to host cells.

Candidalysin: An unlikely aide for fungal gut commensalism.

Fungi colonize the mammalian gastrointestinal (GI) tract and can adopt both commensal and opportunistic lifestyles. In a recent issue of Nature, Liang et al. unraveled the complex interplay between Candida morphotypes and the gut bacterial microbiota and described a key role for candidalysin in gut colonization.1.

Amino acid bites: Microbial snacking influences host metabolism.

The gut microbiota has the capacity to metabolize food-derived molecules. In this issue of Cell Host & Microbe, Li et al. explore how some bacterial species of the gut microbiota can deplete amino acids in the gut lumen, modulating the amino acid landscape and energy metabolism of the host.

Differential mechanism between Listeria monocytogenes strains with different virulence contaminating ready-to-eat sausages during the simulated gastrointestinal tract.

Listeria monocytogenes exhibits varying levels of pathogenicity when entering the host through contaminated food. However, little is known regarding the stress response and environmental tolerance mechanism of different virulence strains to host gastrointestinal (GI) stimuli. This study analyzed the differences in the survival and genes of stress responses among two strains of L. monocytogenes 10403S (serotype 1/2a, highly virulent strain) and M7 (serotype 4a, low-virulence strain) during simulated gastrointestinal digestion. The results indicated that L. monocytogenes 10403S showed greater acid and bile salt tolerance than L. monocytogenes M7, with higher survival rates and less cell deformation and cell membrane permeability during the in vitro digestion. KEGG analysis of the transcriptomes indicated that L. monocytogenes 10403S displayed significant activity in amino acid metabolism, such as glutamate and arginine, associated with acid tolerance. Additionally, L. monocytogenes 10403S demonstrated a higher efficacy in promoting activities that preserve bacterial cell membrane integrity and facilitate flagellar protein synthesis. These findings will contribute valuable practical insights into the tolerance distinctions among different virulence strains of L. monocytogenes in the GI environment.

Exploring lipid digestion discrepancies between preterm formula and human milk: Insights from in vitro gastrointestinal digestion and the impact of added milk fat.

Lipids play a pivotal role in the nutrition of preterm infants, acting as a primary energy source. Due to their underdeveloped gastrointestinal systems, lipid malabsorption is common, leading to insufficient energy intake and slowed growth. Therefore, it is critical to explore the reasons behind the low lipid absorption rate in formulas for preterm infants. This study utilized a simulated in intro gastrointestinal digestion model to assess the differences in lipid digestion between preterm human milk and various infant formulas. Results showed that the fatty acid release rates for formulas IF3, IF5, and IF7 were 58.90 %, 56.58 %, and 66.71 %, respectively, lower than human milk's 72.31 %. The primary free fatty acids (FFA) and 2-monoacylglycerol (2-MAG) released during digestion were C14:0, C16:0, C18:0, C18:1n-9, and C18:2n-6, in both human milk and formulas. Notably, the higher release of C16:0 in formulas may disrupt fatty acid balance, impacting lipid absorption. Further investigations are necessary to elucidate lipid absorption differences, which will inform the optimization of lipid content in preterm infant formulas.

UMobileNetV2 model for semantic segmentation of gastrointestinal tract in MRI scans.

Gastrointestinal (GI) cancer is leading general tumour in the Gastrointestinal tract, which is fourth significant reason of tumour death in men and women. The common cure for GI cancer is radiation treatment, which contains directing a high-energy X-ray beam onto the tumor while avoiding healthy organs. To provide high dosages of X-rays, a system needs for accurately segmenting the GI tract organs. The study presents a UMobileNetV2 model for semantic segmentation of small and large intestine and stomach in MRI images of the GI tract. The model uses MobileNetV2 as an encoder in the contraction path and UNet layers as a decoder in the expansion path. The UW-Madison database, which contains MRI scans from 85 patients and 38,496 images, is used for evaluation. This automated technology has the capability to enhance the pace of cancer therapy by aiding the radio oncologist in the process of segmenting the organs of the GI tract. The UMobileNetV2 model is compared to three transfer learning models: Xception, ResNet 101, and NASNet mobile, which are used as encoders in UNet architecture. The model is analyzed using three distinct optimizers, i.e., Adam, RMS, and SGD. The UMobileNetV2 model with the combination of Adam optimizer outperforms all other transfer learning models. It obtains a dice coefficient of 0.8984, an IoU of 0.8697, and a validation loss of 0.1310, proving its ability to reliably segment the stomach and intestines in MRI images of gastrointestinal cancer patients.

Exploring the lung-gut direction of the gut-lung axis in patients with ARDS.

Acute respiratory distress syndrome (ARDS) represents a life-threatening inflammatory reaction marked by refractory hypoxaemia and pulmonary oedema. Despite advancements in treatment perspectives, ARDS still carries a high mortality rate, often due to systemic inflammatory responses leading to multiple organ dysfunction syndrome (MODS). Indeed, the deterioration and associated mortality in patients with acute lung injury (LI)/ARDS is believed to originate alongside respiratory failure mainly from the involvement of extrapulmonary organs, a consequence of the complex interaction between initial inflammatory cascades related to the primary event and ongoing mechanical ventilation-induced injury resulting in multiple organ failure (MOF) and potentially death. Even though recent research has increasingly highlighted the role of the gastrointestinal tract in this process, the pathophysiology of gut dysfunction in patients with ARDS remains mainly underexplored. This review aims to elucidate the complex interplay between lung and gut in patients with LI/ARDS. We will examine various factors, including systemic inflammation, epithelial barrier dysfunction, the effects of mechanical ventilation (MV), hypercapnia, and gut dysbiosis. Understanding these factors and their interaction may provide valuable insights into the pathophysiology of ARDS and potential therapeutic strategies to improve patient outcomes.

Strategies to Enhance Cultivation of Anaerobic Bacteria from Gastrointestinal Tract of Chicken.

The gastrointestinal tract (GIT) of chicken is a complex ecosystem harboring trillions of microbes that play a pivotal role in the host's physiology, digestion, nutrient absorption, immune system maturation, and prevention of pathogen intrusion. For optimal animal health and productivity, it is imperative to characterize these microorganisms and comprehend their role. While the GIT of poultry holds a reservoir of microorganisms with potential probiotic applications, most of the diversity remains unexplored. To enhance our understanding of uncultured microbial diversity, concerted efforts are required to bring these microorganisms into culture. Isolation and cultivation of GIT-colonizing microorganisms yield reproducible material, including cells, DNA, and metabolites, offering new insights into metabolic processes in the environment. Without cultivation, the role of these organisms in their natural settings remains unclear and limited to a descriptive level. Our objective is to implement cultivation strategies aimed at improving the isolation of a diverse range of anaerobic microbes from the chicken's GIT, leveraging multidisciplinary knowledge from animal physiology, animal nutrition, metagenomics, feed biochemistry, and modern cultivation strategies. Additionally, we aim to implement the use of proper practices for sampling, transportation, and media preparation, which are known to influence isolation success. Appropriate methodologies should ensure a consistent oxygen-free environment, optimal atmospheric conditions, appropriate host incubation temperature, and provision for specific nutritional requirements in alignment with their distinctive needs. By following these methodologies, cultivation will not only yield reproducible results for isolation but will also facilitate isolation procedures, thus fostering a comprehensive understanding of the intricate microbial ecosystem within the chicken's GIT.

Vairimorpha (Nosema) ceranae can promote Serratia development in honeybee gut: an underrated threat for bees?

The genus Serratia harbors opportunistic pathogenic species, among which Serratia marcescens is pathogenic for honeybees although little studied. Recently, virulent strains of S. marcescens colonizing the Varroa destructor mite's mouth were found vectored into the honeybee body, leading to septicemia and death. Serratia also occurs as an opportunistic pathogen in the honeybee's gut with a low absolute abundance. The Serratia population seems controlled by the host immune system, but its presence may represent a hidden threat, ready to arise when honeybees are weakened by biotic and abiotic stressors. To shed light on the Serratia pathogen, this research aims at studying Serratia's development dynamics in the honeybee body and its interactions with the co-occurring fungal pathogen Vairimorpha ceranae. Firstly, the degree of pathogenicity and the ability to permeate the gut epithelial barrier of three Serratia strains, isolated from honeybees and belonging to different species (S. marcescens, Serratia liquefaciens, and Serratia nematodiphila), were assessed by artificial inoculation of newborn honeybees with different Serratia doses (104, 106, and 108 cells/mL). The absolute abundance of Serratia in the gut and in the hemocoel was assessed in qPCR with primers targeting the luxS gene. Moreover, the absolute abundance of Serratia was assessed in the gut of honeybees infected with V. ceranae at different development stages and supplied with beneficial microorganisms and fumagillin. Our results showed that all tested Serratia strains could pass through the gut epithelial barrier and proliferate in the hemocoel, with S. marcescens being the most pathogenic. Moreover, under cage conditions, Serratia better proliferates when a V. ceranae infection is co-occurring, with a positive and significant correlation. Finally, fumagillin and some of the tested beneficial microorganisms could control both Serratia and Vairimorpha development. Our findings suggest a correlation between the two pathogens under laboratory conditions, a co-occurring infection that should be taken into consideration by researches when testing antimicrobial compounds active against V. ceranae, and the related honeybees survival rate. Moreover, our findings suggest a positive control of Serratia by the environmental microorganism Apilactobacillus kunkeei in a in vivo model, confirming the potential of this specie as beneficial bacteria for honeybees.

CT findings in seven dogs with perforating wooden skewer foreign bodies from the gastrointestinal tract.

Background: Perforating foreign bodies from the gastrointestinal tract, such as wooden skewers, are reported in the small animal literature producing inflammatory/infectious lesions in the thorax, abdomen, and musculoskeletal system, which can be life-threatening in some instances. Several imaging modalities have been used, and advanced imaging techniques have shown a great advantage in its diagnosis and pre-surgical planning. Aim: The objective of this study is to describe the computed tomographic findings in a group of seven medium to large breed dogs with perforating wooden skewers and foreign bodies migrated from the gastrointestinal tract. Methods: The medical records database was searched for dogs with a suspected diagnosis of a perforating wooden foreign body migrated from the gastrointestinal tract in which a computed tomographic study was performed. Signalment, history, and clinicopathological findings (when available) were retrieved, and the computed tomographic studies were reviewed. Results: Clinical signs vary depending on the anatomical regions affected through the perforating pathway. All foreign bodies were identified and showed a median attenuation of 79 HU, with the most common localization being the stomach followed by the jejunum. Peritoneal fat stranding surrounding the perforation site was the most frequent computed tomographic finding. The presence of peritoneal free fluid and/or gas was uncommon. Pleural effusion, pulmonary perforation, and pneumothorax were present in most of the cases with the foreign body traversing the pleural space. Pulmonary cavitary lesions were always reported when the ending tip of the wooden skewer was within the pulmonary parenchyma. Soft tissue abscessation was recognized in all cases where the ending tip was lodged in muscular or subcutaneous tissues. Conclusion: Findings supported the variability of the secondary lesions caused by this type of foreign body and the utility of computed tomography in their recognition, as well as in the identification of the wooden skewer.

Isolation of Myenteric and Submucosal Plexus from Mouse Gastrointestinal Tract and Subsequent Co-Culture with Small Intestinal Organoids.

Intestinal homeostasis results from the proper interplay among epithelial cells, the enteric nervous system (ENS), interstitial cells of Cajal (ICCs), smooth muscle cells, the immune system, and the microbiota. The disruption of this balance underpins the onset of gastrointestinal-related diseases. The scarcity of models replicating the intricate interplay between the ENS and the intestinal epithelium highlights the imperative for developing novel methods. We have pioneered a sophisticated tridimensional in vitro technique, coculturing small intestinal organoids with myenteric and submucosal neurons. Notably, we have made significant advances in (1) refining the isolation technique for culturing the myenteric plexus, (2) enhancing the isolation of the submucosal plexus-both yielding mixed cultures of enteric neurons and glial cells from both plexuses, and (3) subsequently co-culturing myenteric and submucosal neurons with small intestinal organoids. This co-culture system establishes neural innervations with intestinal organoids, allowing for the investigation of regulatory interactions in the context of gastrointestinal diseases. Furthermore, we have developed a method for microinjecting the luminal space of small intestinal organoids with fluorescently labeled compounds. This technique possesses broad applicability such as the assessment of intestinal permeability, transcytosis, and immunocytochemical and immunofluorescence applications. This microinjection method could be extended to alternative experimental setups, incorporating bacterial species, or applying treatments to study ENS-small intestinal epithelium interactions. Therefore, this technique serves as a valuable tool for evaluating the intricate interplay between neuronal and intestinal epithelial cells (IECs) and shows great potential for drug screening, gene editing, the development of novel therapies, the modeling of infectious diseases, and significant advances in regenerative medicine. The co-culture establishment process spans twelve days, making it a powerful asset for comprehensive research in this critical field.

Gastrointestinal digestion behavior and bioavailability of greenly prepared highly loaded myofibrillar-luteolin vehicle.

In this study, the highly loaded myofibrillar protein (MP)-luteolin (Lut) complexes were noncovalently constructed by using green high-pressure homogenization technology (HPH) and high-pressure micro-fluidization technology (HPM), aiming to optimize the encapsulation efficiency of flavonoids in the protein-based vehicle without relying on the organic solvent (i.e. DMSO, ethanol, etc.). The loading efficiency of Lut into MPs could reach 100 % with a concentration of 120 µmol/g protein by using HPH (103 MPa, 2 passes) without ethanol adoption. The in vitro gastrointestinal digestion behavior and antioxidant activity of the complexes were then compared with those of ethanol-assisted groups. During gastrointestinal digestion, the MP digestibility of complexes, reaching more than 70.56 % after thermal treatment, was higher than that of sole protein. The release profile of Lut encapsulated in ethanol-containing and ethanol-free samples both well fitted with the Hixson-Crowell release kinetic model (R2 = 0.92 and 0.94, respectively), and the total phenol content decreased by ≥ 40.02 % and ≥ 62.62 %, respectively. The in vitro antioxidant activity (DPPH, ABTS, and Fe2+) of the digestive products was significantly improved by 23.89 %, 159.69 %, 351.12 % (ethanol groups) and 13.43 %, 125.48 %, 213.95 % (non-ethanol groups). The 3 mg/mL freeze-dried digesta significantly alleviated lipid accumulation and oxidative stress in HepG2 cells. The triglycerides and malondialdehyde contents decreased by at least 57.62 % and 67.74 % after digesta treatment. This study provides an easily approached and environment-friendly strategy to construct a highly loaded protein-flavonoid conjugate, which showed great potential in the formulation of healthier meat products.

Time maters: Exploring the dynamics of bioactive compounds content, bioaccessibility and antioxidant activity during Lupinus angustifolius germination.

Germination is a process that enhances the content of health-promoting secondary metabolites. However, the bioaccessibility of these compounds depends on their stability and solubility throughout the gastrointestinal tract. The study aimed to explore how germination time influences the content and bioaccessibility of γ-aminobutyric acid and polyphenols and antioxidant capacity of lupin (Lupinus angustifolius L.) sprouts during simulated gastrointestinal digestion. Gamma-aminobutyric acid showed a decrease following gastrointestinal digestion (GID) whereas phenolic acids and flavonoids exhibited bioaccessibilities of up to 82.56 and 114.20%, respectively. Although the digestion process affected the profile of phenolic acids and flavonoids, certain isoflavonoids identified in 7-day sprouts (G7) showed resistance to GID. Germination not only favored antioxidant activity but also resulted in germinated samples exhibiting greater antioxidant properties than ungerminated counter parts after GID. Intestinal digests from G7 did not show cytotoxicity in RAW 264.7 macrophages, and notably, they showed an outstanding ability to inhibit the production of reactive oxygen species. This suggests potential benefit in mitigating oxidative stress. These findings contribute to understand the dynamic interplay between bioprocessing and digestion in modulating the bioaccessibility of bioactive compounds in lupin, thereby impacting health.

Novel approaches in IBD therapy: targeting the gut microbiota-bile acid axis.

Inflammatory bowel disease (IBD) is a chronic and recurrent condition affecting the gastrointestinal tract. Disturbed gut microbiota and abnormal bile acid (BA) metabolism are notable in IBD, suggesting a bidirectional relationship. Specifically, the diversity of the gut microbiota influences BA composition, whereas altered BA profiles can disrupt the microbiota. IBD patients often exhibit increased primary bile acid and reduced secondary bile acid concentrations due to a diminished bacteria population essential for BA metabolism. This imbalance activates BA receptors, undermining intestinal integrity and immune function. Consequently, targeting the microbiota-BA axis may rectify these disturbances, offering symptomatic relief in IBD. Here, the interplay between gut microbiota and bile acids (BAs) is reviewed, with a particular focus on the role of gut microbiota in mediating bile acid biotransformation, and contributions of the gut microbiota-BA axis to IBD pathology to unveil potential novel therapeutic avenues for IBD.

Does "all disease begin in the gut"? The gut-organ cross talk in the microbiome.

The human microbiome, a diverse ecosystem of microorganisms within the body, plays pivotal roles in health and disease. This review explores site-specific microbiomes, their role in maintaining health, and strategies for their upkeep, focusing on oral, lung, vaginal, skin, and gut microbiota, and their systemic connections. Understanding the intricate relationships between these microbial communities is crucial for unraveling mechanisms underlying human health. Recent research highlights bidirectional communication between the gut and distant microbiome sites, influencing immune function, metabolism, and disease susceptibility. Alterations in one microbiome can impact others, emphasizing their interconnectedness and collective influence on human physiology. The therapeutic potential of gut microbiota in modulating distant microbiomes offers promising avenues for interventions targeting various disorders. Through interdisciplinary collaboration and technological advancements, we can harness the power of the microbiome to revolutionize healthcare, emphasizing microbiome-centric approaches to promote holistic well-being while identifying areas for future research.

Enterococcus faecalis: implications for host health.

The microbiota represents a crucial area of research in maintaining human health due to its potential for uncovering novel biomarkers, therapies, and molecular mechanisms relevant to population identification and experimental model characterization. Among these microorganisms, Enterococcus faecalis, a Gram-positive bacterium found in the gastrointestinal tract of humans and animals, holds particular significance. Strains of this bacterial species have sparked considerable debate in the literature due to their dual nature; they can either be utilized as probiotics in the food industry or demonstrate resistance to antibiotics, potentially leading to severe illness, disability, and death. Given the diverse characteristics of Enterococcus faecalis strains, this review aims to provide a comprehensive understanding of their impact on various systems within the host, including the immunological, cardiovascular, metabolic, and nervous systems. Furthermore, we summarize the bacterium-host interaction characteristics and molecular effects to highlight their targets, features, and overall impact on microbial communities and host health.

Ethanolamine metabolism through two genetically distinct loci enables Klebsiella pneumoniae to bypass nutritional competition in the gut.

Successful microbial colonization of the gastrointestinal (GI) tract hinges on an organism's ability to overcome the intense competition for nutrients in the gut between the host and the resident gut microbiome. Enteric pathogens can exploit ethanolamine (EA) in the gut to bypass nutrient competition. However, Klebsiella pneumoniae (K. pneumoniae) is an asymptomatic gut colonizer and, unlike well-studied enteric pathogens, harbors two genetically distinct ethanolamine utilization (eut) loci. Our investigation uncovered unique roles for each eut locus depending on EA utilization as a carbon or nitrogen source. Murine gut colonization studies demonstrated the necessity of both eut loci in the presence of intact gut microbiota for robust GI colonization by K. pneumoniae. Additionally, while some Escherichia coli gut isolates could metabolize EA, other commensals were incapable, suggesting that EA metabolism likely provides K. pneumoniae a selective advantage in gut colonization. Molecular and bioinformatic analyses unveiled the conservation of two eut loci among K. pneumoniae and a subset of the related taxa in the K. pneumoniae species complex, with the NtrC-RpoN regulatory cascade playing a pivotal role in regulation. These findings identify EA metabolism as a critical driver of K. pneumoniae niche establishment in the gut and propose microbial metabolism as a potential therapeutic avenue to combat K. pneumoniae infections.

Human gut-associated Bifidobacterium species salvage exogenous indole, a uremic toxin precursor, to synthesize indole-3-lactic acid via tryptophan.

Indole in the gut is formed from dietary tryptophan by a bacterial tryptophan-indole lyase. Indole not only triggers biofilm formation and antibiotic resistance in gut microbes but also contributes to the progression of kidney dysfunction after absorption by the intestine and sulfation in the liver. As tryptophan is an essential amino acid for humans, these events seem inevitable. Despite this, we show in a proof-of-concept study that exogenous indole can be converted to an immunomodulatory tryptophan metabolite, indole-3-lactic acid (ILA), by a previously unknown microbial metabolic pathway that involves tryptophan synthase ß subunit and aromatic lactate dehydrogenase. Selected bifidobacterial strains converted exogenous indole to ILA via tryptophan (Trp), which was demonstrated by incubating the bacterial cells in the presence of (2-13C)-labeled indole and l-serine. Disruption of the responsible genes variedly affected the efficiency of indole bioconversion to Trp and ILA, depending on the strains. Database searches against 11,943 bacterial genomes representing 960 human-associated species revealed that the co-occurrence of tryptophan synthase ß subunit and aromatic lactate dehydrogenase is a specific feature of human gut-associated Bifidobacterium species, thus unveiling a new facet of bifidobacteria as probiotics. Indole, which has been assumed to be an end-product of tryptophan metabolism, may thus act as a precursor for the synthesis of a host-interacting metabolite with possible beneficial activities in the complex gut microbial ecosystem.

New methods to unveil host-microbe interaction mechanisms along the microbiota-gut-brain-axis.

Links between the gut microbiota and human health have been supported throughout numerous studies, such as the development of neurological disease disorders. This link is referred to as the "microbiota-gut-brain axis" and is the focus of an emerging field of research. Microbial-derived metabolites and gut and neuro-immunological metabolites regulate this axis in health and many diseases. Indeed, assessing these signals, whether induced by microbial metabolites or neuro-immune mediators, could significantly increase our knowledge of the microbiota-gut-brain axis. However, this will require the development of appropriate techniques and potential models. Methods for studying the induced signals originating from the microbiota remain crucial in this field. This review discusses the methods and techniques available for studies of microbiota-gut-brain interactions. We highlight several much-debated elements of these methodologies, including the widely used in vivo and in vitro models, their implications, and perspectives in the field based on a systematic review of PubMed. Applications of various animal models (zebrafish, mouse, canine, rat, rabbit) to microbiota-gut-brain axis research with practical examples of in vitro methods and innovative approaches to studying gut-brain communications are highlighted. In particular, we extensively discuss the potential of "organ-on-a-chip" devices and their applications in this field. Overall, this review sheds light on the most widely used models and methods, guiding researchers in the rational choice of strategies for studies of microbiota-gut-brain interactions.