BACKGROUND Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as ...BACKGROUND Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are longitudinally and tightly controlled by numerous factors including a wide range of distinct regulatory proteins. However, the sequence of events associated with colon mucosal repair after colitis and the evolution of the luminal content characteristics during this process have been little studied.AIM To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis.METHODS C57 BL/6 male mice were given 3.5% dextran sodium sulfate(DSS) in drinking water for 5 d. They were euthanized 2(day 7), 5(day 10), 8(day 13), and 23(day28) d after DSS removal. The colonic luminal environment and epithelial repair processes during the inflammatory flare and colitis resolution were analyzed with reference to a non-DSS treated control group, euthanized at day 0. Epithelial repair events were assessed histo-morphologically in combination with functional permeability tests, expression of key inflammatory and repairing factors, and evaluation of colon mucosa-adherent microbiota composition by 16 S rRNA sequencing.RESULTS The maximal intensity of colitis was concomitant with maximal alterations of intestinal barrier function and histological damage associated with goblet cell depletion in colon mucosa. It was recorded 2 d after termination of the DSStreatment, followed by a progressive return to values similar to those of control mice. Although signs of colitis were severe(inflammatory cell infiltrate, crypt disarray, increased permeability) and associated with colonic luminal alterations(hyperosmolarity, dysbiosis, decrease in short-chain fatty acid content), epithelial healing processes were launched early during the inflammatory flare with increased gene expression of certain key epithelial repair modulators, including transforming growth factor-β, interleukin(Il)-15, Il-22, Il-33, and serum amyloid A. Whereas signs of inflammation progressively diminished, luminal colonic environment alterations and microscopic abnormalities of colon mucosa persisted long after colitis induction.CONCLUSION This study shows that colon repair can be initiated in the context of inflamed mucosa associated with alterations of the luminal environment and highlights the longitudinal involvement of key modulators.展开更多
Colorectal cancer(CRC)is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States.Considering the risk factors of CRC,dietary therapy has ...Colorectal cancer(CRC)is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States.Considering the risk factors of CRC,dietary therapy has become one of the most effective approaches in reducing CRC morbidity and mortality.The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases.As the most common types of microbes used as probiotics,lactic acid bacteria(LAB)are comprised of an ecologically diverse group of microorganisms united by formation of lactic acid as the primary metabolite of sugar metabolism.LAB have been successfully used in managing diarrhea,food allergies,and inflammatory bowel disease.LAB also demonstrated a host of properties in preventing colorectal cancer development by inhibiting initiation or progression through multiple pathways.In this review,we discuss recent insights into cellular and molecular mechanisms of LAB in CRC prevention including apoptosis,antioxidant DNA damages,immune responses,and epigenetics.The emerging experimental findings from clinical trials as well as the proposed mechanisms of gut microbiota in carcinogenesis will also be briefly discussed.展开更多
<strong>Background:</strong> The question of where to hospitalize extremely malnourished patients with anorexia nervosa (AN) is a real dilemma. On one hand, psychiatrists have to deal with severe medical c...<strong>Background:</strong> The question of where to hospitalize extremely malnourished patients with anorexia nervosa (AN) is a real dilemma. On one hand, psychiatrists have to deal with severe medical complications that are not within their competences and that justify hospitalization in an internal medicine ward. On the other hand, medical doctors have to face psychic decompensations that would justify admission to a psychiatric ward. In this context, we share our experience of management of severely malnourished AN adult patients in a transdisciplinary specialized eating disorders (ED) unit, referral center for AN associated with somatic severity. <strong>Method:</strong> First, we described the modalities of care proposed to patients with AN hospitalized in the medical unit. Intensive medical care, both somatic and psychiatric, are provided thanks to a transdisciplinary therapeutic program, where objectives are to: medically stabilize the patient, initiate progressive refeeding and start supportive psychotherapy before being transferred to a psychiatric ED unit. Secondly, we conducted a retrospective descriptive study that included all adult patients with AN admitted for the first time to the unit, between November 1997 and January 2014, for severe malnutrition and/or complications of the ED. Objective was to specify patients’ characteristics: demographic, nutritional status, history of ED, care pathway. <strong>Results: </strong>Among a cohort of 386 adult patients with AN (21 males and 365 females) admitted for the first time in the unit, mean age was 29.4 (±11.5) years, mean BMI was 12.7 (±2.2) kg/m<sup>2</sup>. Before being supported in the unit, 78.2% of patients had already been hospitalized in other hospitals. Mean length of stay was 35.2 days. Patients were clinically serious and unstable because of life-threatening somatic complications due to a low BMI. During hospital stay, a temporary transfer to medical intensive care unit was necessary for 25.6% of patients. Average patient weight gain was 0.777 kg per week and 81.9% of patients benefited from enteral nutrition.<strong> Conclusion: </strong>This specialized transdisciplinary unit where physician nutritionists and psychiatrists coordinate medical care together, allow a better understanding and management of extreme malnutrition associated with AN. Thanks to their expertise, care teams are less critical and less rejecting towards patients. Thus, therapeutic alliance could be optimized.展开更多
基金grants from the Societe Francaise de Nutrition and the Association Francois AupetitVidal-Lletjos S was a recipient of a PhD grant from INRA-Universite Paris-Saclay(ALIAS program)
文摘BACKGROUND Mucosal healing has become a therapeutic goal to achieve stable remission in patients with inflammatory bowel diseases. To achieve this objective, overlapping actions of complex cellular processes, such as migration, proliferation, and differentiation, are required. These events are longitudinally and tightly controlled by numerous factors including a wide range of distinct regulatory proteins. However, the sequence of events associated with colon mucosal repair after colitis and the evolution of the luminal content characteristics during this process have been little studied.AIM To document the evolution of colon mucosal characteristics during mucosal healing using a mouse model with chemically-induced colitis.METHODS C57 BL/6 male mice were given 3.5% dextran sodium sulfate(DSS) in drinking water for 5 d. They were euthanized 2(day 7), 5(day 10), 8(day 13), and 23(day28) d after DSS removal. The colonic luminal environment and epithelial repair processes during the inflammatory flare and colitis resolution were analyzed with reference to a non-DSS treated control group, euthanized at day 0. Epithelial repair events were assessed histo-morphologically in combination with functional permeability tests, expression of key inflammatory and repairing factors, and evaluation of colon mucosa-adherent microbiota composition by 16 S rRNA sequencing.RESULTS The maximal intensity of colitis was concomitant with maximal alterations of intestinal barrier function and histological damage associated with goblet cell depletion in colon mucosa. It was recorded 2 d after termination of the DSStreatment, followed by a progressive return to values similar to those of control mice. Although signs of colitis were severe(inflammatory cell infiltrate, crypt disarray, increased permeability) and associated with colonic luminal alterations(hyperosmolarity, dysbiosis, decrease in short-chain fatty acid content), epithelial healing processes were launched early during the inflammatory flare with increased gene expression of certain key epithelial repair modulators, including transforming growth factor-β, interleukin(Il)-15, Il-22, Il-33, and serum amyloid A. Whereas signs of inflammation progressively diminished, luminal colonic environment alterations and microscopic abnormalities of colon mucosa persisted long after colitis induction.CONCLUSION This study shows that colon repair can be initiated in the context of inflamed mucosa associated with alterations of the luminal environment and highlights the longitudinal involvement of key modulators.
基金Supported by Grant No.NSFC-81272444 to Zhong LNo.PN-II-ID-PCE-2012-4-0608 Nr.48/02.09.2013 to Covasa M
文摘Colorectal cancer(CRC)is the third leading cause of cancer deaths worldwide and the fourth most common cancer diagnosed among men and women in the United States.Considering the risk factors of CRC,dietary therapy has become one of the most effective approaches in reducing CRC morbidity and mortality.The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases.As the most common types of microbes used as probiotics,lactic acid bacteria(LAB)are comprised of an ecologically diverse group of microorganisms united by formation of lactic acid as the primary metabolite of sugar metabolism.LAB have been successfully used in managing diarrhea,food allergies,and inflammatory bowel disease.LAB also demonstrated a host of properties in preventing colorectal cancer development by inhibiting initiation or progression through multiple pathways.In this review,we discuss recent insights into cellular and molecular mechanisms of LAB in CRC prevention including apoptosis,antioxidant DNA damages,immune responses,and epigenetics.The emerging experimental findings from clinical trials as well as the proposed mechanisms of gut microbiota in carcinogenesis will also be briefly discussed.
文摘<strong>Background:</strong> The question of where to hospitalize extremely malnourished patients with anorexia nervosa (AN) is a real dilemma. On one hand, psychiatrists have to deal with severe medical complications that are not within their competences and that justify hospitalization in an internal medicine ward. On the other hand, medical doctors have to face psychic decompensations that would justify admission to a psychiatric ward. In this context, we share our experience of management of severely malnourished AN adult patients in a transdisciplinary specialized eating disorders (ED) unit, referral center for AN associated with somatic severity. <strong>Method:</strong> First, we described the modalities of care proposed to patients with AN hospitalized in the medical unit. Intensive medical care, both somatic and psychiatric, are provided thanks to a transdisciplinary therapeutic program, where objectives are to: medically stabilize the patient, initiate progressive refeeding and start supportive psychotherapy before being transferred to a psychiatric ED unit. Secondly, we conducted a retrospective descriptive study that included all adult patients with AN admitted for the first time to the unit, between November 1997 and January 2014, for severe malnutrition and/or complications of the ED. Objective was to specify patients’ characteristics: demographic, nutritional status, history of ED, care pathway. <strong>Results: </strong>Among a cohort of 386 adult patients with AN (21 males and 365 females) admitted for the first time in the unit, mean age was 29.4 (±11.5) years, mean BMI was 12.7 (±2.2) kg/m<sup>2</sup>. Before being supported in the unit, 78.2% of patients had already been hospitalized in other hospitals. Mean length of stay was 35.2 days. Patients were clinically serious and unstable because of life-threatening somatic complications due to a low BMI. During hospital stay, a temporary transfer to medical intensive care unit was necessary for 25.6% of patients. Average patient weight gain was 0.777 kg per week and 81.9% of patients benefited from enteral nutrition.<strong> Conclusion: </strong>This specialized transdisciplinary unit where physician nutritionists and psychiatrists coordinate medical care together, allow a better understanding and management of extreme malnutrition associated with AN. Thanks to their expertise, care teams are less critical and less rejecting towards patients. Thus, therapeutic alliance could be optimized.
