Amino Acid Formula Containing Synbiotics in Infants with Cow’s Milk Protein Allergy: A Systematic Review and Meta-Analysis

Cow’s milk protein allergy (CMPA) is associated with dysbiosis of the infant gut microbiome, with allergic and immune development implications. Studies show benefits of combining synbiotics with hypoallergenic formulae, although evidence has never been systematically examined. This review identified seven publications of four randomised controlled trials comparing an amino acid formula (AAF) with an AAF containing synbiotics (AAF-Syn) in infants with CMPA (mean age 8.6 months; 68% male, mean intervention 27.3 weeks, n = 410). AAF and AAF-Syn were equally effective in managing allergic symptoms and promoting normal growth. Compared to AAF, significantly fewer infants fed AAF-Syn had infections (OR 0.35 (95% CI 0.19–0.67), p = 0.001). Overall medication use, including antibacterials and antifectives, was lower among infants fed AAF-Syn. Significantly fewer infants had hospital admissions with AAF-Syn compared to AAF (8.8% vs. 20.2%, p = 0.036; 56% reduction), leading to potential cost savings per infant of £164.05–£338.77. AAF-Syn was associated with increased bifidobacteria (difference in means 31.75, 95% CI 26.04–37.45, p < 0.0001); reduced Eubacterium rectale and Clostridium coccoides (difference in means −19.06, 95% CI −23.15 to −14.97, p < 0.0001); and reduced microbial diversity (p < 0.05), similar to that described in healthy breastfed infants, and may be associated with the improved clinical outcomes described. This review provides evidence that suggests combining synbiotics with AAF produces clinical benefits with potential economic implications.     

Cancer-protective effect of a synbiotic combination between Lactobacillus gasseri 505 and a Cudrania tricuspidata leaf extract on colitis-associated colorectal cancer

ABSTRACT

Previously, a synbiotic combination of probiotic Lactobacillus gasseri 505 (LG) and a new prebiotic, Cudrania tricuspidata leaf extract (CT) in fermented milk, designated FCT, showed an in vitro immunomodulatory effect and antioxidant activity. Although synbiotic combination might have cancer-protective effects, these activities have not been fully validated in vivo. Ten-week treatment of LG, CT, or FCT to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colorectal cancer (CAC) mouse model reduced both the incidence of colonic tumors and damage to the colonic mucosa effectively, suggesting a cancer-protective effect. To understand these, biomarkers associated with inflammation, colon barrier, apoptosis, and cancer cell proliferation were monitored in AOM/DSS group versus LG/CT/FCT groups. A synbiotic combination (FCT) down-regulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) and inflammation-associated enzymes (iNOS and COX-2), and up-regulated anti-inflammatory cytokines (IL-4 and IL-10). In addition, colon barrier experiment revealed that biomarkers of mucus layer (MUC-2 and TFF3) and tight junction (occludin and ZO-1) were up-regulated. Subsequent apoptosis experiment showed that pro-apoptotic factors (p53, p21, and Bax) were up-regulated and anti-apoptotic factors (Bcl-2 and Bcl-xL) were down-regulated. Furthermore, comparative metagenome analysis of gut microbiota revealed that Staphylococcus decreased but Lactobacillus, Bifidobacterium, and Akkermansia increased, supporting their protective effects, accompanied by increased short-chain fatty acids (SCFAs). Taken together, the FCT administration showed cancer-protective effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Consequently, the synbiotic combination (FCT) could be a novel potential health-protective natural agent against CAC.     

含合生元的早期肠内营养对严重烧伤病人血浆内毒素的影响

目的:探讨含合生元的早期肠内营养对严重烧伤病人血浆内毒素血症的影响。方法:随机双盲对照临床研究。40例重度烧伤病人分成含合生元(乳酸菌+纤维素)的早期肠内营养组(治疗组)和仅含纤维素的早期肠内营养组(对照组)。治疗前、伤后D3、D7、D10、D14和D21动态测定血内毒素水平。结果:几乎所有时相点治疗组血浆内毒素水平低于对照组,伤后D10有明显差异(P<0.05)且整个研究过程中治疗组内毒素血症发生率明显低于对照组(36.7%vs49.2%,P<0.05)。治疗组感染并发症较对照组也有所下降。结论:含合生元的早期肠内营养可以改善中毒以上烧伤病人内毒素血症的严重程度,对感染并发症产生了积极的影响。     

Experience of long-term synbiotic therapy in seven short bowel patients with refractory enterocolitis

Background/Purpose

Probiotic and prebiotic therapies are potent new strategies to treat various intestinal diseases, including inflammatory bowel disease and viral and bacterial infections. Synbiotics is defined as the combined use of probiotics and prebiotics and is expected to have a stronger effect on intestinal diseases than probiotics or prebiotics alone, but there has been no report of its clinical application. The authors designed a protocol for synbiotic therapy composed of Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides and preliminarily ascertained its clinical effects in humans.

Methods

This protocol of synbiotic therapy was applied for more than 1 year to 7 malnourished patients with short bowels who suffered from refractory enterocolitis.

Results

The therapeutic protocol improved the intestinal bacterial flora (inducing the domination by anaerobic bacteria and suppressing the residence of pathogenic bacteria) and increased short chain fatty acids in the feces (from 27.8 to 65.09 μmol/g wet feces). All patients but 1 accelerated their body weight gain, and 5 patients showed increased serum rapid turnover proteins.

Conclusions

This protocol for synbiotic therapy might be a potent modulator of intestinal flora and a promising strategy to treat short bowel patients with refractory enterocolitis.     

Does the use of probiotics/synbiotics prevent postoperative infections in patients undergoing abdominal surgery? A meta-analysis of randomized controlled trials

Background  Advances in surgery have considerably lowered postoperative morbidity. However, infection remains a considerable morbidity factor. The aim of this review is to identify the potential benefit(s) of the perioperative administration of probiotics/synbiotics to patients undergoing abdominal surgery. Methods  We searched PubMed, Scopus, Web of Science, and Cochrane library to identify randomized controlled trials (RCTs) that studied the perioperative administration of probiotics/synbiotics to patients undergoing abdominal surgery. Results  Nine RCTs studying 733 patients were included in our review. The incidence of postoperative pneumonia, cholangitis, and any infections as well as the duration of postoperative hospital stay and length of antibiotic therapy were lower among patients receiving probiotics than in the control group [six RCTs, 355 patients, odds ratio (OR) 0.24, 95% confidence interval (CI) 0.09–0.68; three RCTs, 209 patients, OR 0.18, 95% CI 0.05–0.57; seven RCTs, 514 patients, OR 0.26, 95% CI 0.12–0.55; five RCTs, 313 patients, OR −2.70, 95% CI −5.15 to −0.25; four RCTs, 250 patients, OR  −4.01, 95% CI −5.11 to −2.92, respectively], while the incidence of postoperative wound infection, urinary tract infection, intra-abdominal abscess, and mortality was not different between patients of the compared groups (six RCTs, 355 patients, OR 0.52, 95% CI 0.23–1.18; five RCTs, 313 patients, OR 0.44, 95% CI 0.04–5.54; four RCTs, 226 patients, OR 0.44, 95% CI  0.12–1.59; nine RCTs, 685 patients, OR 0.98, 95% CI 0.29–3.29, respectively). Conclusion  The use of probiotics/synbiotics may reduce postoperative infections after abdominal surgery. This is a promising infection-preventive measure that may decrease morbidity, length of antibiotic therapy, duration of hospital stay, and pressure for emergence of antimicrobial resistance. However, the results of this meta-analysis should be interpreted with caution due to the significant heterogeneity of the studies included.     

Clinical assessment of synbiotics for treating chronic kidney disease: A protocol for systematic review and meta-analysis

Background:This research aims to evaluate the efficacy and safety of synbiotics for treating chronic kidney disease.Methods:Related articles written in English were sourced from EMBASE, PubMed, Cochrane Library, and China National Knowledge Infrastructure. These articles were used in the evaluation of the effect of synbiotics for treating chronic kidney disease. The extent of the relationship was assessed by calculating the pooled risk ratio, mean differences or standardized mean difference along with the equivalent 95% confidence intervals. The risk of bias introduced through each study was considered by adopting the Cochrane Risk of Bias Tool. Suitable statistical research methods were utilized for the synthesis of the data. The RevMan 5.3 software was used to conduct all statistical analysis.Results:The final results of the current study is due to be included in a peer-reviewed journal.Conclusion:The final remarks of the current study will be useful evidence for determining whether synbiotics is an effective and safe therapeutic method for treating chronic kidney disease.OSF registration number:DOI 10.17605/OSF.IO/UASF4 (https://osf.io/uasf4/).     

Nutrition Support and Infections Associated With Hepatic Resection and Liver Transplantation in Patients With Chronic Liver Disease

Malnutrition is common in liver cirrhotic patients who will undergo liver resection or liver transplantation. A precise evaluation of their nutrition status is thus difficult because of the presence of ascites and the edema caused by their impaired protein synthesis. Both perioperative enteral and parenteral nutrition have benefits in reducing the morbidity and mortality of liver surgery, and in general, oral nutrition supplements are recommended. Branched‐chain amino acids (BCAAs) promote protein and glycogen synthesis and regulate immune system function. Synbiotics, a combination of pro‐ and prebiotics, is reported to enhance immune responses. Oral nutrition support with BCAAs, synbiotics, and an immune‐enhancing diet have a beneficial effect on preventing the perioperative infections associated with hepatic resection or liver transplantation.     

Probiotic Supplementation for Promotion of Growth in Children: A Systematic Review and Meta-Analysis

Probiotics are commonly prescribed to promote a healthy gut microbiome in children. Our objective was to investigate the effects of probiotic supplementation on growth outcomes in children 0–59 months of age. We conducted a systematic review and meta-analysis which included randomized controlled trials (RCTs) that administered probiotics to children aged 0–59 months, with growth outcomes as a result. We completed a random-effects meta-analysis and calculated a pooled standardized mean difference (SMD) or relative risk (RR) and reported with a 95% confidence interval (CI). We included 79 RCTs, 54 from high-income countries (HIC), and 25 from low- and middle-income countries (LMIC). LMIC data showed that probiotics may have a small effect on weight (SMD: 0.26, 95% CI: 0.11–0.42, grade-certainty = low) and height (SMD 0.16, 95% CI: 0.06–0.25, grade-certainty = moderate). HIC data did not show any clinically meaningful effect on weight (SMD: 0.01, 95% CI: −0.04–0.05, grade-certainty = moderate), or height (SMD: −0.01, 95% CI: −0.06–0.04, grade-certainty = moderate). There was no evidence that probiotics affected the risk of adverse events. We conclude that in otherwise healthy children aged 0–59 months, probiotics may have a small but heterogenous effect on weight and height in LMIC but not in children from HIC.     

The Impact of Probiotics,Prebiotics, and Synbiotics during Pregnancy or Lactation on the Intestinal Microbiota of Children Born by Cesarean Section: A Systematic Review

The gut microbiota is a key factor in the correct development of the gastrointestinal immune system. Studies have found differences between the gut microbiota of newborns delivered by cesarean section compared to those vaginally delivered. Our objective was to evaluate the effect of ingestion of probiotics, prebiotics, or synbiotics during pregnancy and/or lactation on the development of the gut microbiota of the C-section newborns. We selected experimental studies in online databases from their inception to October 2021. Of the 83 records screened, 12 met the inclusion criteria. The probiotics used belonged to the genera Lactobacillus, Bifidobacterium, Propionibacterium, and Streptococcus, or a combination of those, with dosages varying between 2 × 10⁶ and 9 × 10¹¹ CFU per day, and were consumed during pregnancy and/or lactation. Probiotic strains were combined with galacto-oligosaccharides, fructo-oligosaccharides, or bovine milk-derived oligosaccharides in the synbiotic formulas. Probiotic, prebiotic, and synbiotic interventions led to beneficial gut microbiota in cesarean-delivered newborns, closer to that in vaginally delivered newborns, especially regarding Bifidobacterium colonization. This effect was more evident in breastfed infants. The studies indicate that this beneficial effect is achieved when the interventions begin soon after birth, especially the restoration of bifidobacterial population. Changes in the infant microbial ecosystem due to the interventions seem to continue after the end of the intervention in most of the studies. More interventional studies are needed to elucidate the optimal synbiotic combinations and the most effective strains and doses for achieving the optimal gut microbiota colonization of C-section newborns.