Maud Robert

Metabolic and bariatric surgery (MBS) modifies the gastrointestinal tract, gut microbiota composition, as well as metabolic and hormonal functions, influencing eating behaviour. These changes following MBS could explain the variability in weight loss between patients.The BARIA-gut-TASTE trial aims to assess the impact of nutritional counselling to promote gut microbiota diversity versus standard nutritional counselling provided after MBS on gut microbiota composition and function, food behaviour, sensory alterations and weight loss and its maintenance. The BARIA-gut-TASTE trial is a prospective, single blind, randomized, controlled trial with two parallel groups, involving patients undergoing MBS, recruited at Lyon University Hospital.The primary outcome is the change in gut microbiota diversity between baseline and 1-year post-surgery. The main secondary outcomes include change in gut microbiota function, eating behaviour and preferences, appetite, anthropometric measurements, sensory function, cardio-metabolic profile, compliance, and mental health parameters.Patients will be enrolled before surgery during a routine care hospital visit. They will then be followed up at 3, 6, and 12 months after surgery through visits combining clinical care and research assessments (sampling, ad libitum buffet meal, sensory tests and questionnaires). The dietary interventions specific to each group will be provided from months 3 to 12 after MBS. The BARIA-gut-TASTE trial will lead to a better understanding of the interrelationships between MBS-induced modification in gut microbiota composition and function, food preferences and behaviour related to weight loss. Ultimately, the BARIA-gut-TASTE trial could contribute to improving obesity care by personalizing bariatric procedures and post-MBS management.

Aims/hypothesis Timely metabolic surgery improves glycaemic control and reduces cardiovascular risk for patients with type 2 diabetes. Young age is a known predictor of favourable metabolic outcome, but Roux-en-Y gastric bypass (RYGB) is often delayed owing to reported surgical and psychological risks in young adults. We hypothesised that use of RYGB in adults aged 18–35 years would result in higher rates of diabetes remission compared with older individuals, without an associated increase in morbidity. Methods We analysed prospective registry data from three expert centres where young adults (29.5±5 years) and older adults (48±6.8 years) (means ± SD) who were living with non-insulin-dependent type 2 diabetes underwent RYGB. Younger adults were matched in a 1:2 ratio to their older counterparts for duration of preoperative diabetes, sex, BMI and American Society of Anesthesiologists physical status score. The rates of diabetes remission and adverse events in both groups were compared five years postoperatively. Results A total of 79.1% (53/67) of the young adults and 76.9% (103/134) of the older adults attended the 5 year follow-up. Diabetes remission occurred earlier and more frequently in the young adult group, with an HR of 2.92 (95% CI 1.13, 7.59; p=0.027) and a median time to remission of 6 months (95% CI 3.1, 8.9), compared with 24 months (95% CI 10.9, 37.1) for older adults (p=0.001). There were no significant differences in all-cause adverse events, percentage weight change or loss to follow-up between groups. Conclusions/interpretation Diabetes remission occurred earlier and more frequently in young adults within the first 5 years after RYGB. Surgical complications, nutritional deficiency or suboptimal weight loss were not different in the investigated young adult group compared with the older adults.

Background: Obesity is a well-known risk factor for cancer. We have previously reported the role of adipose-tissue-derived mesenchymal stem cells from obese individuals (ob-ASC) in the promotion of pathogenic Th17 cells and immune check point (ICP) upregulation. Thus, we postulated herein that this mechanism could contribute to breast cancer (BC) aggressiveness. Methods: Conditioning medium (CM) from mitogen-activated ob-ASC and immune cell co-cultures were added to two human breast cancer cell line (BCCL) cultures. Expressions of pro-inflammatory cytokines, angiogenesis markers, metalloproteinases, and PD-L1 (a major ICP) were measured at the mRNA and/or protein levels. BCCL migration was explored in wound healing assays. Anti-cytokine neutralizing antibodies (Ab) were added to co-cultures. Results: CM from ob-ASC/MNC co-cultures increased IL-1β, IL-8, IL-6, VEGF-A, MMP-9, and PD-L1 expressions in both BCCLs and accelerated their migration. The use of Abs demonstrated differential effects for IL-17A and IFNγ on BCCL pro-inflammatory cytokine over-expression or PD-L1 upregulation, respectively, but potentiating effects on BCCL migration. Finally, co-cultures with ob-ASC, but not lean ASC, enhanced PD-L1 expression. Conclusions: Our results demonstrate increased inflammation and ICP markers and accelerated BCCL migration following the activation of pathogenic Th17 cells by ob-ASC, which could represent a new mechanism linking obesity with BC progression.

Background Marginal ulcers (MU) after gastric bypass are a challenging problem. The first-line treatment is a medical therapy with eviction of risk factors but is sometimes insufficient. The management strategies of intractable ulcers are still not clearly defined. The aim of our study was to analyse the risk factors for recurrence, the management strategies used and their efficiencies. Methods Based on a retrospective analysis of all MU managed in our tertiary care centre of bariatric surgery during the last 14 years, a descriptive analysis of the cohort, the management strategies and their efficiency were analysed. A logistic regression was done to identify the independent associated risk factors of intractable ulcer. Results Fifty-six patients matched inclusion criteria: 30 were referred to us (13 Roux-en-Y Gastric Bypass—RYGB and 17 One Anastomosis Gastric Bypass—OAGB), 26 were operated on in our institution (24 RYGB and 2 OAGB). 11 patients had a complicated inaugural MU requiring an interventional procedure in emergency: 7 perforations, 4 haemorrhages. The majority of MU were treated medically as a first-line therapy (n = 45; 80.4%). 32 MU recurred: 20 patients required surgery as a 2nd line therapy, 6 were operated on as a 3rd line therapy and 1 had a surgery as a 5th line therapy. The OAGB was the only risk factor of recurrence (p = 0.018). We found that the Surgical management was significantly more frequent for patients with a OAGB (84% versus 35% for RYGB, p = 0.001); the most performed surgical procedure was a conversion of OAGB to RYGB (n = 11, 37.9%). Conclusion Surgery was required for a large number of MU especially in case of recurrence, but recurrence can still occur after the surgery. The OAGB was the only risk factor of recurrence identified and conversion to RYGB seemed to be effective for the healing.

Changes in food preferences after bariatric surgery may alter its effectiveness as a treatment for obesity. We aimed to compare food reward for a comprehensive variety of food categories between patients who received a sleeve gastrectomy (SG) or a Roux-en-Y gastric bypass (RYGB) and to explore whether food reward differs according to weight loss. In this cross-sectional exploratory study, food reward was assessed using the Leeds Food Preference Questionnaire (LFPQ) in patients at 6, 12, or 24 months after SG or RYGB. We assessed the liking and wanting of 11 food categories. Comparisons were done regarding the type of surgery and total weight loss (TWL; based on tertile distribution). Fifty-six patients (30 SG and 26 RYGB) were included (women: 70%; age: 44.0 (11.1) y). Regarding the type of surgery, scores were not significantly different between SG and RYGB, except for ‘non-dairy products—without color’ explicit liking (p = 0.04). Regarding TWL outcomes, explicit liking, explicit wanting, and implicit wanting, scores were significantly higher for good responders than low responders for ‘No meat—High fat’ (post-hoc corrected p-value: 0.04, 0.03, and 0.04, respectively). Together, our results failed to identify major differences in liking and wanting between the types of surgery and tended to indicate that higher weight loss might be related to a higher reward for high protein-content food. Rather focus only on palatable foods, future studies should also consider a broader range of food items, including protein reward.

The PD-L1/PD-1 immune checkpoint axis is the strongest T cell exhaustion inducer. As immune dysfunction occurs during obesity, we analyzed the impact of obesity on PD-L1/PD-1 expression in white adipose tissue (WAT) in mice and in human white adipocytes. We found that PD-L1 was overexpressed in WAT of diet-induced obese mice and was associated with increased expression of PD-1 in visceral but not subcutaneous WAT. Human in vitro cocultures with adipose-tissue-derived mesenchymal stem cells (ASC) and mononuclear cells demonstrated that the presence of ASC harvested from obese WAT (i) enhanced PD-L1 expression as compared with ASC from lean WAT, (ii) decreased Th1 cell cytokine secretion, and (iii) resulted in decreased cytolytic activity towards adipocytes. Moreover, (iv) the implication of PD-L1 in obese ASC-mediated T cell dysfunction was demonstrated through PD-L1 blockade. Finally, (v) conditioned media gathered from these cocultures enhanced PD-L1 expression in freshly differentiated adipocytes, depending on IFNγ. Altogether, our results suggest that PD-L1 is overexpressed in the WAT of obese individuals during IFNγ secretion, leading to T cell dysfunction and notably reduced cytolytic activity. Such a mechanism could shed light on why adipose-tissue-infiltrating viruses, such as SARS-CoV-2, can worsen disease in obese individuals.