The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBTand the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host-microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.
Biomarkers ; Gastrointestinal Microbiome ; Graft Rejection ; immunology ; Humans ; Immunity, Mucosal ; Intestine, Small ; microbiology ; transplantation ; Metagenomics ; Transplantation Tolerance ; immunology

OBJECTIVETo observe the effects of astragalus polysaccharide (AP) on the intestinal mucosal morphology, level of secretory IgA (s-IgA) in intestinal mucus, and distribution of T lymphocyte subsets in Peyer's patch in rats with severe scald injury.

METHODSOne hundred and thirty SD rats were divided into sham injury group (SI, sham injured, n = 10), scald group (S, n = 30), low dosage group (LD, n = 30), moderate dosage group (MD, n = 30), and high dosage group (HD, n = 30) according to the random number table. Rats in the latter 4 groups were inflicted with 30% TBSA full-thickness scald on the back. From post injury hour 2, rats in groups LD, MD, and HD were intraperitoneally injected with 0.5 mL AP solution with the dosage of 100, 200, and 300 mg/kg each day respectively, and rats in group S were injected with 0.5 mL normal saline instead. Ten rats from group SI immediately after injury and 10 rats from each of the latter 4 groups on post injury day (PID) 3, 7, 14 were sacrificed, and their intestines were harvested. The morphology of ileal mucosa was examined after HE staining; the level of s-IgA in ileal mucus was determined with double-antibody sandwich ELISA method; the proportions of CD3⁺, CD4⁺, CD8⁺ T lymphocytes in Peyer's patches of intestine were determined with flow cytometer, and the proportion of CD4⁺ to CD8⁺ was calculated. Data were processed with one-way analysis of variance, analysis of variance of factorial design, and SNK test.

RESULTS(1) Villi in normal form and intact villus epithelial cells were observed in rats of group SI immediately after injury, while edema of villi and necrosis and desquamation of an enormous amount of villi were observed in groups with scalded rats on PID 3, with significant infiltration of inflammatory cells. On PID 7, no obvious improvement in intestinal mucosal lesion was observed in groups with scalded rats. On PID 14, the pathology in intestinal mucosa of rats remained nearly the same in group S, and it was alleviated obviously in groups LD and MD, and the morphology of intestinal mucosa of rats in group HD was recovered to that of group SI. (2) On PID 3, 7, and 14, the level of s-IgA in intestinal mucus significantly decreased in groups S, LD, MD, and HD [(43 ± 5), (45 ± 5), (46 ± 5) µg/mL; (47 ± 5), (48 ± 5), (49 ± 6) µg/mL; (50 ± 6), (51 ± 5), (52 ± 5) µg/mL; (53 ± 6), (54 ± 5), (55 ± 5) µg/mL] as compared with that of rats in group SI immediately after injury [(69 ± 4) µg/mL, with P values below 0.05]. The level of s-IgA in intestinal mucus of rats in group MD was significantly higher than that in group S at each time point (with P values below 0.05), and that of group HD was significantly higher than that in groups S and LD at each time point (with P values below 0.05). (3) Compared with those of rats in group SI immediately after injury, the proportions of CD3⁺ T lymphocytes and CD4⁺ T lymphocytes significantly decreased in groups with scalded rats at each time point (with P values below 0.05), except for those in group HD on PID 14. The proportion of CD4⁺ T lymphocytes of rats in group LD was significantly higher than that in group S on PID 3 (P < 0.05). The proportions of CD3⁺ T lymphocytes and CD4⁺ T lymphocytes were significantly higher in groups MD and HD than in groups S and LD (except for the proportion of CD4⁺ T lymphocytes in group MD on PID 3 and 14) at each time point (with P values below 0.05). The proportion of CD3⁺ T lymphocytes on PID 7 and 14 and that of CD4⁺ T lymphocytes on PID 3 were significantly higher in group HD than in group MD (with P values below 0.05). Compared with that of rats in group SI immediately after injury, the proportion of CD8⁺ T lymphocytes significantly increased in the other 4 groups at each time point (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group LD on PID 7 and 14 and groups MD and HD at each time point than in group S (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group MD on PID 7 and 14 and group HD at each time point than in group LD (with P values below 0.05). The proportion of CD8⁺ T lymphocytes was significantly lower in rats of group HD on PID 7 and 14 than in group MD (with P values below 0.05). On PID 3, 7, and 14, the proportion of CD4⁺ to CD8⁺ was significantly lower in groups S, LD, MD, and HD (0.65 ± 0.11, 0.68 ± 0.13, 0.73 ± 0.22; 0.76 ± 0.15, 0.78 ± 0.14, 0.90 ± 0.10; 0.85 ± 0.21, 0.89 ± 0.18, 1.08 ± 0.19; 0.99 ± 0.20, 1.05 ± 0.21, 1.25 ± 0.23) as compared with that of rats in group SI immediately after injury (1.74 ± 0.20, with P values below 0.05). The proportion of CD4⁺ to CD8⁺ was significantly higher in rats of group HD than in group MD on PID 7 (P < 0.05), and the proportion was significantly higher in these two groups than in group S at each time point (with P values below 0.05). The proportion of CD4⁺ to CD8⁺ was significantly higher in rats of group MD on PID 14 and group HD at each time point than in group LD (with P values below 0.05). Compared within each group, the proportions of CD3⁺, CD4⁺, CD8⁺ T lymphocytes and the proportion of CD4⁺ to CD8⁺ of rats in groups LD, MD, and HD showed a trend of gradual elevation along with passage of time.

CONCLUSIONSAP can improve the injury to intestinal mucosa and modulate the balance of T lymphocyte subsets in Peyer's patch in a time- and dose-dependent manner, and it can promote s-IgA secretion of intestinal mucosa in a dose-dependent manner.

Animals ; Astragalus Plant ; adverse effects ; Burns ; immunology ; pathology ; physiopathology ; Dose-Response Relationship, Drug ; Immunity, Mucosal ; Immunoglobulin A ; metabolism ; Intestinal Mucosa ; metabolism ; physiology ; Intestine, Small ; metabolism ; Peyer's Patches ; immunology ; physiopathology ; Polysaccharides ; Rats ; Rats, Sprague-Dawley ; Soft Tissue Injuries ; T-Lymphocyte Subsets ; immunology

Mucosal immune responses against Pygidiopsis summa (Trematoda: Heterophyidae) infection were studied in ICR mice. Experimental groups consisted of group 1 (uninfected controls), group 2 (infection with 200 metacercariae), and group 3 (immunosuppression with Depo-Medrol and infection with 200 metacercariae). Worms were recovered in the small intestine at days 1, 3, 5, and 7 post-infection (PI). Intestinal intraepithelial lymphocytes (IEL), mast cells, and goblet cells were counted in intestinal tissue sections stained with Giemsa, astra-blue, and periodic acid-Schiff, respectively. Mucosal IgA levels were measured by ELISA. Expulsion of P. summa from the mouse intestine began to occur from days 3-5 PI which sustained until day 7 PI. The worm expulsion was positively correlated with proliferation of IEL, mast cells, goblet cells, and increase of IgA, although in the case of mast cells significant increase was seen only at day 7 PI. Immunosuppression suppressed all these immune effectors and inhibited worm reduction in the intestine until day 7 PI. The results suggested that various immune effectors which include IEL, goblet cells, mast cells, and IgA play roles in regulating the intestinal mucosal immunity of ICR mice against P. summa infection.
Animals ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Goblet Cells/immunology ; Heterophyidae/*immunology ; *Immunity, Mucosal ; Immunoglobulin A/analysis ; Intestine, Small/parasitology/pathology ; Leukocyte Count ; Lymphocytes/immunology ; Male ; Mast Cells/immunology ; Mice ; Mice, Inbred ICR ; Parasite Load ; Time Factors ; Trematode Infections/*immunology/parasitology

Immunoglobulin G4 (IgG4)-related sclerosing disease is rare and is known to involve various organs. We present a case of histologically proven IgG4-related sclerosing disease of the small bowel with imaging findings on computed tomography (CT) and small bowel series. CT showed irregular wall thickening, loss of mural stratification and aneurysmal dilatation of the distal ileum. Small bowel series showed aneurysmal dilatations, interloop adhesion with traction and abrupt angulation.
Adult ; Antibodies, Anti-Idiotypic/immunology ; Autoimmune Diseases/*diagnosis/immunology ; Humans ; Immunoglobulin G/*immunology ; Intestine, Small/*pathology/radiography ; Male ; Multidetector Computed Tomography/*methods ; Sclerosis/diagnosis/immunology

In intestinal helminth infections, Th2 immune respones are generally associated with mucin secretion for worm expulsion from the host intestine. In particular, IL-4 and IL-13 are the important cytokines related with intestinal mucus production via STAT6 signalling in nematode infections. However, this perspective has never been studied in Gymnophalloides seoi infection. The present study aimed to observe the STAT6 signalling and cytokine responses in C57BL/6 mice, a mouse strain resistant to infection with this trematode. The results showed that worm expulsion occurred actively during days 1-2 post-infection (PI), when goblet cells began to proliferate in the small intestine. The STAT6 gene expression in the mouse spleen became remarkable from day 2 PI. Moreover, G. seoi infection induced a significant increase of IL-13 from day 4 PI in the spleen of infected mice. Our results suggested that goblet cell hyperplasia and worm expulsion in G. seoi-infected mice should be induced by STAT6 signalling, in which IL-13 may be involved as a dominant triggering cytokine.
Animals ; Crassostrea ; Female ; Goblet Cells/*pathology ; Hyperplasia/pathology ; Interleukin-13/*metabolism ; Interleukin-4/*metabolism ; Intestine, Small/immunology ; Metacercariae ; Mice ; Mice, Inbred C57BL ; STAT6 Transcription Factor/*metabolism ; Signal Transduction ; Specific Pathogen-Free Organisms ; Spleen/immunology ; Trematoda/*immunology ; Trichinellosis/*immunology/parasitology

OBJECTIVETo reveal the efficacy on early postoperative inflammatory small bowel obstruction (EPISBO) treated with electroacupuncture and acupuncture separately and make the comparison of the efficacy difference.

METHODSThrough retrospective analysis, 459 cases of EPISBO were divided into an electroacupuncture group (355 cases) and an acupuncture group (104 cases). Based on routine treatment, Zusanli (ST 36), Shangjuxu (ST 37), Taichong (LR 3), Gongsun (SP 4) and Xuanzhong (GB 39) were selected in either group, but stimulated with electroacupuncture and acupuncture separately, once per day, for 30 min each time.

RESULTSAll of 459 cases were cured. The average days of curative achievement in electroacupuncture group were less apparently than those in acupuncture group (13.5 +/- 7.5 vs. 20.8 +/- 6.5, P < 0.05). The days of curative achievement in either group were less significantly than those treated with parenteral nutrition and medication recorded in literatures (32.0 +/- 7.0, both P < 0.05).

CONCLUSIONEither electroacupuncture or acupuncture achieves a significant efficacy on EPISBO, but the efficacy of electroacupuncture is better than that of acupuncture.

Acupuncture Therapy ; Adult ; Aged ; Electroacupuncture ; Female ; Humans ; Inflammatory Bowel Diseases ; therapy ; Intestinal Obstruction ; immunology ; therapy ; Intestine, Small ; immunology ; surgery ; Male ; Middle Aged ; Postoperative Complications ; immunology ; therapy ; Retrospective Studies ; Young Adult

OBJECTIVETo investigate the effect and mechanism of FTY720 on acute graft versus host disease (GVHD) in rat small bowel transplantation (SBTx).

METHODSHeterotopic SBTx was performed using a parent (WF)-into-F1 (WFxACI) rat combination. Recipient rats were divided into experimental group (n=6) and control group (n=6). Rats in the experimental group were administered with FTY720 at 0.5 mg/kg for 14 days. Lymphocyte apoptosis in the liver and the mucosa of intestine and graft was detected by TUNEL and flow cytometry 15 days after transplantation. Recipient survival and lymphocyte apoptosis were compared between the two groups.

RESULTSRecipients in the control group died of GVHD after a mean survival time of (16+/-2.1) days. FTY720-treated recipients had a significantly longer survival (>100 days). After administration of FTY720, the percentage of apoptotic lymphocytes was significantly increased in the graft as compared to that in the control group by flow cytometry. The ratio of apoptotic lymphocyte in the liver and graft was also significantly higher in the experimental group by TUNEL.

CONCLUSIONFTY720 effectively induces the lymphocyte apoptosis, inhibits the lesion of target tissues by GVHD, and prolongs the recipient survival.

Animals ; Apoptosis ; drug effects ; Fingolimod Hydrochloride ; Graft vs Host Disease ; immunology ; prevention & control ; Immunosuppressive Agents ; pharmacology ; Intestine, Small ; transplantation ; Lymphocytes ; cytology ; drug effects ; Male ; Propylene Glycols ; pharmacology ; Rats ; Rats, Inbred WF ; Sphingosine ; analogs & derivatives ; pharmacology ; Transplantation, Heterotopic

OBJECTIVETo investigate the correlation between major histocompatibility complex (MHC) class I chain-related gene A (MICA) gene alleles matching rates and graft rejection in small intestine, liver and kidney transplantation.

METHODSGenome DNA were extracted from blood samples or pathological sections collected from donors and recipients of living-related transplantation, included 4 cases of small bowel transplantation, 5 cases of liver transplantation and 6 cases of kidney transplantation. The correlation between MICA alleles matching rates and acute graft rejection was analyzed following 13 MICA alleles determination by polymerase chain reaction based on sequence-specific primers (PCR-SSP).

RESULTSHLA zygosity of all donors and recipients was confirmed to be half-matching. The recipients displaying higher matching rates of MICA alleles with donors showed lighter clinical and pathological rejection and longer survival time. On the contrary, recipients with lower matching rates of MICA alleles with donors showed severer clinical and pathological rejection and shorter survival time relatively.

CONCLUSIONMatching rates of MICA alleles has negative relevance to acute rejection, and positive relevance to survival time of recipients in small bowel, liver, and kidney transplantation.

Alleles ; Graft Rejection ; genetics ; immunology ; Histocompatibility Antigens Class I ; genetics ; Humans ; Intestine, Small ; transplantation ; Kidney Transplantation ; immunology ; Liver Transplantation ; immunology ; Living Donors ; Organ Transplantation

OBJECTIVETo investigate the effects of early enteral nutrition supplemented with immune nutrient on intestine immune function in mice with severe burn.

METHODSTwenty-four BALB/c mice were inflicted with 20% TBSA full-thickness scald, then they were randomly divided into EN(with oral administration of common enteral nutrition after 2 hours) and EIN (with oral administration of common enteral nutrition and glutamine, arginine after 2 hours) groups. Another 10 mice were used as the normal control (NC) group. The supplied energy ratio( carbohydrate: fat: protein)in former 2 groups was 82:3:15, and the ratio of energy to nitrogen was 150: 1. The energy requirement of each mouse was calculated according to 732.2 kJ x kg(-1) x d(-1), one third of the requirement was administrated on 1st day, and one half of it on 2nd day, and full energy requirement was started on the 3rd day,and the requirement was divided into 4-6 portions every day. The feed was isocaloric, isonitrogenous, and isovolumic for the 2 experimental groups. All mice were sacrificed and entire small intestine was harvested for determination of intestinal IgA level by ELISA, total Peyer's patches (PP) lymphocytes and their apoptosis ratio, and changes in PP lymphocytes (CD3+, CD4+, CD19+) on 7th day of the experiment.

RESULTSCompared with those in NC group [(4.5 +/- 0.6) x 10(6), (42 +/- 7) microg/cm, respectively], total PP lymphocytes and intestinal IgA levels in EN and EIN groups obviously decreased [(2.3 +/- 0.4) x 10(6), (35 +/- 6) microg/cm, (3.8 +/- 0. 5) x 10(6), (38 +/- 6), microg/cm, respectively, P < 0.05] , among which the values in EIN group were higher than EN group (P < 0.05). The changes in PP lymphocytes were similar to that of total PP lymphocytes. Compared with that in NC group [(4.8 +/- 2.1)%], the apoptosis ratio of PP lymphocytes in EN and EIN groups significantly increased [(12.7 +/- 2.4)%, (8.0 +/- 1.7)%, respectively, P < 0.05], however the ratio in EIN group was lower than that of EN group (P < 0.05).

CONCLUSIONSEarly enteral nutrition supplemented with immune nutrient can improve intestinal immune function in mice with severe burn.

Animals ; Burns ; immunology ; physiopathology ; therapy ; Enteral Nutrition ; Intestine, Small ; immunology ; Intestines ; immunology ; Lymphocyte Subsets ; Lymphocytes ; immunology ; Male ; Mice ; Mice, Inbred BALB C

OBJECTIVETo investigate the pathologic monitoring of intestinal graft rejection in auxiliary en-bloc liver-small bowel transplantation in pigs.

METHODSFifty outbred long-white pigs were randomized into three groups, and the auxiliary composite liver-small bowel allotransplantations were undertaken in 10 pigs in group A and group B while segment small bowel allotransplantations were undertaken in 10 pigs in group C. Group A and C were not treated with immunosuppressive drugs while group B was treated with cyclosporine A and methylprednisolone. The postoperative intestinal graft rejections were monitored by biopsy through the jejunostomy or ileuostomy on 1, 3, 5, 7, 14, 21 and 30 days after operation. Through routine management, the specimens were directly examined via optical and electronic microscope respectively.

RESULTSAs shown from pathological data, the median initial time of postoperative rejection in group A was 8 days (ranged from 7 to 12), later than that in group C (5 days:ranged from 3 to 5), P<0.05). On the 7th day postoperatively, the rejection scores in group A was 1.11+/-0.20, lower than that in group C(2.56+/-0.18, P<0.05), but higher than that in group B(0.20+/-0.13, P<0.05). Ultrastructure also showed more severe intestinal graft rejection in intestinal transplantation than that in combined transplantation. The median survival time was 9 days(ranged from 7 to 25) in group A and 12 days(ranged from 7 to 20) in group C, while all the pigs in group B lived longer than 30 days.

CONCLUSIONThe pathological assessment through the jejunostomy or ileuostomy biopsy is a convenient method to monitor the postoperative graft rejections in intestinal related transplantation.

Animals ; Female ; Graft Rejection ; prevention & control ; Graft Survival ; Intestine, Small ; pathology ; transplantation ; ultrastructure ; Liver Transplantation ; adverse effects ; immunology ; Male ; Swine ; Transplantation, Homologous