The spleen is a very hostile environment for tumor cells due to its anatomic location, blood supply, and rich immunological property – which makes it one of the most unique organ to be involved in metastatic diseases.15 Splenic metastases from non-hematologic malignancies are rare ranging from 0.6 to 7.1% base on autopsy reports of cancer patients, and 1.1 to 3.4% base on review of splenectomy cases.14 Moreover, isolated splenic metastases are more infrequent with only 31 cases reported from 1969 to October 2015.16 A splenic abscess is an unusual formation and is usually caused by hematogenous spread from an infection. Such expected frequency varies in different autopsy studies between 0.14% and 0.7%.1 Albeit rare, abscess can also result from migration of gut flora brought about by direct invasion of tumor cells from a neighboring neoplasm.17 This is a case of a 36-year-old female who came in with a history of abdominal pain, chills and fever for seven months. CT scan of the whole abdomen revealed splenic abscess with suspicion of a splenic rupture. The patient underwent exploratory laparotomy with abscess evacuation, splenectomy and double barrel colostomy and given with intravenous antibiotics. Histopathology results showed metastatic adenocarcinoma in the spleen. Thorough deliberation of her case was done and she was eventually managed as a case of Colon Cancer Stage IV and underwent chemotherapy. Splenic abscess developing from splenic metastasis from a colonic adenocarcinoma is rare and with concomitant high mortality rate. More often than not, splenic metastasis is discovered in advanced stage together with metastatic tumor in other organs while isolated splenic metastasis is even more uncommon. A splenic abscess as an initial demonstration of a colon cancer is not a common daily encounter of physicians hence a high index of suspicion coupled with sensitive and specific imaging is necessary in order to provide prompt medical and surgical intervention.

Human ; Female ; Adult: 25-44 Yrs Old ; Abdomen ; Adenocarcinoma ; Autopsy ; Colostomy ; Gastrointestinal Microbiome ; Pain ; Research Report ; Infections ; History ; Splenic Rupture ; World Health Organization ; Neoplasms ; Disease ; Fever ; Hematologic Neoplasms

OBJECTIVES: The gut microbiota plays a crucial role in the pathophysiology of various types of diabetes. However, the causal relationship between them has yet to be systematically elucidated. This study aims to explore the potential causal associations between gut microbiota and diabetes using a two-sample Mendelian randomization (MR) analysis, based on multiple taxonomic levels. METHODS: Eligible instrumental variables were extracted from the selected genome-wide association study (GWAS) data on gut microbiota. These were combined with GWAS datasets on type 1 diabetes (T1D), type 2 diabetes (T2D), and gestational diabetes mellitus (GDM) to conduct forward MR analysis, sensitivity analysis, reverse MR analysis, and validation of significant estimates. Microbial taxa with causal effects on T1D, T2D, and GDM were identified based on a comprehensive assessment of all analytical stages. RESULTS: A total of 2 179, 2 176, and 2 166 single nucleotide polymorphisms (SNP) were included in the MR analyses for gut microbiota with T1D, T2D, and GDM, respectively. MR results indicated causal associations between: Six microbial taxa (Eggerthella, Lachnospira, Bacillales, Desulfovibrionales, Parasutterella, and Turicibacter) and T1D; 9 microbial taxa (Verrucomicrobia, Deltaproteobacteria, Actinomycetales, Desulfovibrionale, Actinomycetaceae, Desulfovibrionaceae, Actinomyces, Alcaligenaceae, and Lachnospiraceae NC2004 group) and T2D; 10 microbial taxa (Betaproteobacteria, Coprobacter, Ruminococcus2, Tenericutes, Clostridia, Methanobacteria, Mollicutes, Methanobacteriales, Methanobacteriaceae, and Methanobrevibacter) and GDM. CONCLUSIONS This study identified specific gut microbial taxa that may significantly increase or decrease the risk of developing diabetes. Some findings were fully replicated in independent validation datasets. However, the underlying biological mechanisms of these causal relationships warrant further investigation through mechanistic studies and population-based research.
Gastrointestinal Microbiome/genetics* ; Humans ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Diabetes Mellitus, Type 2/genetics* ; Diabetes Mellitus, Type 1/genetics* ; Female ; Polymorphism, Single Nucleotide ; Diabetes, Gestational/genetics* ; Pregnancy

In recent years, gut microbiota has been increasingly recognized as a key player in ethanol metabolism and the development of related diseases. On one hand, ethanol intake directly affects the gut, leading to significant alterations in microbial diversity and composition. On the other hand, gut microbiota influences ethanol-induced damage to various organs, especially the liver, through multiple metabolic byproducts (such as short-chain fatty acids like butyrate, propionate, and acetate), modulation of immune responses, alteration of intestinal barrier function, and regulation of ethanol-metabolizing enzymes. Given the close association between gut microbiota and ethanol metabolism, the gut microbiome presents a promising therapeutic target for alcohol-related liver diseases. This review summarizes recent advances in understanding how gut microbiota affects ethanol metabolism, aiming to elucidate its role in the onset and progression of ethanol-related diseases and to provide a theoretical basis and novel targets for microbiota-based interventions.
Gastrointestinal Microbiome/physiology* ; Ethanol/metabolism* ; Humans ; Fatty Acids, Volatile/metabolism* ; Liver Diseases, Alcoholic/metabolism* ; Animals ; Alcohol Drinking/metabolism*

Multiple myeloma (MM) is a common hematologic malignancy that originates from precursor conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Identifying its risk factors is crucial for early intervention. The etiology of MM is multifactorial, involving race, familial clustering, gender, age, obesity, cytogenetic abnormalities, and environmental exposures. Among these, cytogenetic abnormalities and modifiable factors play pivotal roles in MM pathogenesis and progression. 1) cytogenetic abnormalities. Primary abnormalities [e.g., hyperdiploidy, t(11;14), t(14;16)] emerge at the MGUS stage, while secondary abnormalities [e.g., 1q+, del(17p)] drive disease progression. The accumulation of 1q+ promotes clonal evolution, and del(17p) is associated with significantly reduced survival. 2) modifiable risk factors. Obesity promotes MM via the acetyl-CoA synthetase 2 (ACSS2)-interferon regulatory factor 4 (IRF4) pathway. Vitamin D deficiency weakens immune surveillance. Exposure to herbicides such as Agent Orange and glyphosate increases MGUS incidence. Insufficient UV exposure, by reducing vitamin D synthesis, elevates MM risk. Gut microbiota dysbiosis (enrichment of nitrogen-cycle bacteria and depletion of short-chain fatty acids producers) induces chromosomal instability through the ammonium ion-solute carrier family 12 member 22 (SLC12A2)-NEK2 axis. Therefore, risk-based screening among high-risk populations (e.g., those who are obese, elderly, or chemically exposed), along with early interventions targeting cytogenetic abnormalities [e.g., B cell lymphoma 2 (Bcl-2) inhibitors for t(11;14), ferroptosis inducers for t(4;14)] and modifiable factors (e.g., vitamin D supplementation, gut microbiota modulation), may effectively delay disease progression and improve prognosis.
Humans ; Multiple Myeloma/epidemiology* ; Risk Factors ; Obesity/complications* ; Chromosome Aberrations ; Monoclonal Gammopathy of Undetermined Significance/etiology* ; Gastrointestinal Microbiome ; Vitamin D Deficiency/complications* ; Precancerous Conditions/genetics*

OBJECTIVES: Recent evidence suggests that the gut may be a primary site of metformin action. However, studies on the effects of metformin on gut microbiota remain limited, and its impact on gut microbial metabolites such as short-/medium-chain fatty acids is unclear. This study aims to investigate the effects of metformin on gut microbiota, short-/medium-chain fatty acids, and associated metabolic benefits in high-fat diet rats. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 3 groups: 1) Normal diet group (ND group), fed standard chow; 2) high-fat diet group (HFD group), fed a high-fat diet; 3) high-fat diet + metformin treatment group (HFD+Met group), fed a high-fat diet for 8 weeks, followed by daily intragastric administration of metformin solution (150 mg/kg body weight) starting in week 9. At the end of the experiment, all rats were sacrificed, and serum, liver, and colonic contents were collected for assessment of glucose and lipid metabolism, liver pathology, gut microbiota composition, and the concentrations of short-/medium-chain fatty acids. RESULTS: Metformin significantly improved HFD-induced glucose and lipid metabolic disorders and liver injury. Compared with the HFD group, the HFD+Met group showed reduced abundance of Blautia, Romboutsia, Bilophila, and Bacteroides, while Lactobacillus abundance significantly increased (all P<0.05). Colonic contents of butyric acid, 2-methyl butyric acid, valeric acid, octanoic acid, and lauric acid were significantly elevated (all P<0.05), whereas acetic acid, isoheptanoic acid, and nonanoic acid levels were significantly decreased (all P<0.05). Spearman correlation analysis revealed that Lactobacillus abundance was negatively correlated with body weight gain and insulin resistance, while butyrate and valerate levels were negatively correlated with insulin resistance and liver injury (all P<0.05). CONCLUSIONS Metformin significantly increases the abundance of beneficial bacteria such as Lactobacillus and promotes the production of short-/medium-chain fatty acids including butyric, valeric, and lauric acid in the colonic contents of HFD rats, suggesting that metformin may regulate host metabolism through modulation of the gut microbiota.
Animals ; Metformin/pharmacology* ; Rats, Sprague-Dawley ; Diet, High-Fat/adverse effects* ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Fatty Acids, Volatile/metabolism* ; Fatty Acids/metabolism*

The relationship between gut microbiota and depressive disorder has become a research focus in recent years. Within the microbiota-gut-brain axis, the gut microbiota influences the onset and progression of depressive disorder primarily through the tryptophan metabolic pathway. Tryptophan, an essential amino acid in humans, is subject to dual regulation by intestinal microorganisms, which modulate its metabolic balance via inflammatory stimulation and microbial metabolite production. In depression, excessive activation of the kynurenine branch of tryptophan metabolism leads to the accumulation of proinflammatory and neurotoxic metabolites, thereby exacerbating neuroinflammation in the brain. Intervention studies indicate that the antidepressant-like effects of probiotics and traditional Chinese medicine are associated with remodeling of the gut microbiota, restoration of tryptophan metabolic balance, and alleviation of neuroinflammation. Furthermore, targeted inhibition of kynurenine 3-monooxygenase can mitigate neuroinflammation by regulating microglial activity, thus improving depressive-like behaviors. In summary, the metabolite-inflammation axis represents a central node in the interaction regulation between tryptophan metabolism and the microbiota-gut-brain axis. This provides a theoretical foundation for developing novel therapeutic strategies targeting depression through modulation of gut microbiota-mediated tryptophan metabolism.
Tryptophan/metabolism* ; Gastrointestinal Microbiome/physiology* ; Humans ; Depressive Disorder/microbiology* ; Probiotics/therapeutic use* ; Brain/metabolism* ; Kynurenine/metabolism* ; Metabolic Networks and Pathways ; Animals ; Medicine, Chinese Traditional

Chronic urticaria (CU) is a persistent immune-mediated skin disease with an incompletely understood pathogenesis. As the largest micro-ecosystem in the human body, the gut microbiota participates in complex metabolic processes and produces a wide range of metabolites. The gut microbiota-metabolism axis plays a crucial role in the onset and progression of CU. Patients with CU commonly exhibit gut dysbiosis, characterized by a reduction in beneficial bacteria and an increase in opportunistic pathogens, accompanied by alterations in key metabolites. These changes may disrupt the intestinal barrier and modulate the function of immune cells such as mast cells and T cells, thereby triggering or aggravating distal cutaneous inflammation and contributing to CU pathophysiology. Certain bacterial taxa and metabolites hold promise as potential biomarkers for CU diagnosis, therapeutic response, and prognosis, while interventions targeting gut microbiota have demonstrated potential in ameliorating CU symptoms. Elucidating the characteristics and mechanistic roles of gut microbiota and metabolism in CU could provide a theoretical basis for developing novel individualized diagnostic and therapeutic strategies.
Humans ; Gastrointestinal Microbiome/physiology* ; Chronic Urticaria/etiology* ; Dysbiosis/complications* ; Mast Cells

OBJECTIVES: As early as the Apollo 11 mission, astronauts experienced ocular, skin, and upper airway irritation after lunar dust (LD) was brought into the return cabin, drawing attention to its potential biological toxicity. However, the biological effects of LD exposure through the digestive system remain poorly understood. This study aimed to evaluate the impact of digestive exposure to lunar dust simulant (LDS) on gut microbiota and on the intestine, liver, kidney, lung, and bone in mice. METHODS: Eight-week-old female C57BL/6J mice were used. LDS was used as a substitute for lunar dust, and Shaanxi loess was used as Earth dust (ED). Mice were randomly divided into a phosphate buffered saline (PBS) group, an ED group (500 mg/kg), and a LDS group (500 mg/kg), with assessments at days 7, 14, and 28. Mice were gavaged once every 3 days, with body weight recorded before each gavage. At sacrifice, fecal samples were analyzed by 16S ribosomal RNA (rRNA) sequencing; inflammatory cytokine expression [interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α)] in intestinal, liver, and lung tissues was measured by real-time reverse transcription PCR (real-time RT-PCR); hematoxylin and eosin (HE) staining was performed on lung, liver, and intestinal tissues; Periodic acid-Schiff (PAS) staining was used to assess the integrity of the intestinal mucus barrier, and immunohistochemical staining was performed to evaluate the expression of mucin-2 (MUC2). Serum biochemical tests assessed hepatic and renal function. Femoral bone mass was analyzed by micro-computed tomography (micro-CT); osteoblasts and osteoclasts were assessed by osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) staining. Bone marrow immune cell subsets were analyzed by flow cytometry. RESULTS: At day 10, weight gain was slowed in ED and LDS groups. At days 22 and 28, body weight in both ED and LDS groups was significantly lower than controls (both P<0.05). LDS exposure increased microbial species richness and diversity at day 7. Compared with the PBS and ED groups, mice in the LDS group showed increased relative abundance of Deferribacterota, Desulfobacterota, and Campylobacterota, and decreased Firmicutes, with increased Helicobacter typhlonius and reduced Lactobacillus johnsonii and Lactobacillusmurinus. HE and PAS staining of the colon showed that mucosal structural disruption and goblet cell loss were more severe in the LDS group. In addition, immunohistochemistry revealed a significant downregulation of MUC2 expression in this group (P<0.05). No obvious pathological alterations were observed in liver HE staining among the 3 groups, and none of the groups exhibited notable hepatic or renal dysfunction. HE staining of the lungs in the ED and LDS groups showed increased perivascular inflammatory cell infiltration (both P<0.05). CONCLUSIONS LDS exposure via the digestive route induces gut dysbiosis, intestinal barrier disruption, pulmonary inflammation, bone loss, and bone marrow immune imbalance. These findings indicate that LD exposure poses potential health risks during future lunar missions. Targeted restoration of beneficial gut microbiota may represent a promising strategy to mitigate LD-related health hazards.
Animals ; Dust ; Mice ; Mice, Inbred C57BL ; Dysbiosis/etiology* ; Female ; Gastrointestinal Microbiome/drug effects* ; Moon ; Liver/metabolism* ; Digestive System/microbiology* ; Lung/metabolism* ; Kidney

Long-term spaceflight exposes astronauts to multiple extreme environmental factors, such as cosmic radiation, microgravity, social isolation, and circadian rhythm disruption, that markedly increase the risk of depressive symptoms, posing a direct threat to mental health and mission safety. However, the underlying biological mechanisms remain complex and incompletely understood. The potential mechanisms of spaceflight-induced depressive symptoms involve multiple domains, including alterations in brain structure and function, dysregulation of neurotransmitters and neurotrophic factors, oxidative stress, neuroinflammation, neuroendocrine system imbalance, and gut microbiota disturbances. Collectively, these changes may constitute the biological foundation of depressive in astronauts during spaceflight. Space-related stressors may increase the risk of depressive symptoms through several pathways: impairing hippocampal neuroplasticity, suppressing dopaminergic and serotonergic system function, reducing neurotrophic factor expression, triggering oxidative stress and inflammatory responses, activating the hypothalamic-pituitary-adrenal axis, and disrupting gut microbiota homeostasis. Future research should integrate advanced technologies such as brain-computer interfaces to develop individualized monitoring and intervention strategies, enabling real-time detection and effective prevention of depressive symptoms to safeguard astronauts' psychological well-being and mission safety.
Space Flight ; Humans ; Astronauts/psychology* ; Depression/physiopathology* ; Gastrointestinal Microbiome ; Weightlessness/adverse effects* ; Oxidative Stress ; Brain/physiopathology* ; Hypothalamo-Hypophyseal System ; Neuronal Plasticity ; Pituitary-Adrenal System

Patients with depression are more likely to have chronic gastrointestinal (GI) symptoms than the general population, but such symptoms are considered only somatic symptoms of depression and lack special attention. There is a chronic lack of appropriate diagnosis and effective treatment for patients with depression accompanied by GI symptoms, and studying the association between depression and GI disorders (GIDs) is extremely important for clinical management. There is growing evidence that depression is closely related to the microbiota present in the GI tract, and the microbiota-gut-brain axis (MGBA) is creating a new perspective on the association between depression and GIDs. Identifying and treating GIDs would provide a key opportunity to prevent episodes of depression and may also improve the outcome of refractory depression. Current studies on depression and the microbially related gut-brain axis (GBA) lack a focus on GI function. In this review, we combine preclinical and clinical evidence to summarize the roles of the microbially regulated GBA in emotions and GI function, and summarize potential therapeutic strategies to provide a reference for the study of the pathomechanism and treatment of depression in combination with GI symptoms.
Humans ; Gastrointestinal Microbiome/physiology* ; Depression/microbiology* ; Gastrointestinal Diseases/physiopathology* ; Brain ; Animals ; Brain-Gut Axis ; Gastrointestinal Tract/microbiology*