Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms

May combine two claims.

No differences in adaptive behaviors (e.g. ability for self-care) were observed based on the ABAS-II questionnaire or repetitive behaviors based on the RBS-R.

“No differences in adaptive behaviors (e.g. ability for self-care) were observed based on the ABAS-II questionnaire or repetitive behaviors based on the RBS-R (data not shown).”

May combine two claims.

Changes in stool consistency were significant for both the BCP only (p = 0.042) and combination treatment (p = 0.015).

“While changes in frequency of normal stools were not significant for either group, changes in stool consistency were significant for both the BCP only (p = 0.042) and combination treatment (p = 0.015)(Tables 3 and S1).”

Probably not a substantial claim: may not pass S3 (load-bearing).

All study participants reported food/taste sensitivity on the GIH.

“All study participants reported food/taste sensitivity on the GIH.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The bovine colostrum product was tested and found to be negative for Escherichia coli, Salmonella, Listeria, coagulase positive Staphylococcus and antibiotic residue.

“The product was tested and found to be negative for Escherichia coli, Salmonella, Listeria, coagulase positive Staphylococcus and antibiotic residue.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The foods most commonly reported to increase in consumption were fruits and meat.

“The foods most commonly reported to increase in consumption were fruits and meat.”

May combine two claims.

Of the participants who were picky eaters at the start of the study, 43% (3/7) had increased appetite and consumption of novel foods on the BCP only treatment, while 14% (1/7) had increased appetite and consumption of novel foods on the combination treatment arm.

“Of those participants, 43% (3/7) had increased appetite and consumption of novel foods on the BCP only treatment, while 14% (1/7) had increased appetite and consumption of novel foods on the combination treatment arm.”

May combine two claims.

Based on the GIH survey, a reduction in certain GI symptoms was observed, specifically pain with stooling, frequency of diarrhea, and consistency.

“Based on the GIH survey, a reduction in certain GI symptoms was observed, specifically pain with stooling, frequency of diarrhea, and consistency.”

May combine two claims.

Both the BCP only and the combination treatment (BCP + B. infantis) were well tolerated in this cohort, with no participants needing to withdraw due to adverse events.

“In general, both the BCP only and the combination treatment (BCP + B. infantis) were well tolerated in this cohort with no participants needing to withdraw due to adverse events.”

• Also stated in: § Discussion · plain

  “Both study supplements were found to be well-tolerated in our cohort with participants experiencing limited and mild adverse events on both treatment arms.”

• AssumptionRests on an assumption: Sleep disturbances, lethargy and hives were not related to treatment.

May combine two claims.

The bovine colostrum product contained negligible amounts of other microbes (<10 cfu/g coliforms, yeasts and molds and <10,000 cfu/g aerobic plate count (APC)), similar to other protein powders generally recognized as safe (GRAS) by the FDA, and is not a significant source of bacteria.

“The product contained negligible amounts of other microbes (<10 cfu/g coliforms, yeasts and molds and <10,000 cfu/g aerobic plate count (APC)), which is similar to other protein powders generally recognized as safe (GRAS) by the Food and Drug Administration (FDA) [52] and is not a significant source of bacteria.”

• cites [52] Dicks CR. GRAS Notice 644: Non-fat dry goat milk and goat whey protein. 2016.Not checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

All study participants were already regular consumers of dairy products.

“However, all of the study participants were already regular consumers of dairy products.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The majority of study participants (n = 7) were reported to be picky eaters by their parents and often consumed self-restricted diets.

“The majority of the study participants (n = 7) were reported to be picky eaters by their parents and often consumed self-restricted diets.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Parents of 3 participants reported that their children did not like the taste of the supplement, although all were compliant with study protocol and completed the study.

“However, parents of 3 participants reported that their children did not like the taste of the supplement, although all were compliant with study protocol and were able to complete the study.”

May combine two claims.

Some participants on both treatments saw a reduction in the frequency of certain GI symptoms, as well as reduced occurrence of particular aberrant behaviors.

“Some participants on both treatments saw a reduction in the frequency of certain GI symptoms, as well as reduced occurrence of particular aberrant behaviors.”

May combine two claims.

There was a trend toward significant decrease in hard stool for week 1 versus week 5 (p = 0.059) and week 1 versus weeks 2-5 (p = 0.082) for the BCP only treatment.

“There was a trend toward significant decrease in hard stool for week 1 versus week 5 (p = 0.059) and week 1 versus weeks 2–5 (p = 0.082) for the BCP only treatment (Table 4).”

May combine two claims.

The most common adverse events were gassiness and weight gain (a positive side effect).

“The most common adverse events were gassiness and weight gain (a positive side effect).”

May combine two claims.

There were no significant differences between treatments in terms of initial ethanol and methanol levels or change in ethanol and methanol levels.

“There were no significant differences between treatments in terms of initial ethanol and methanol levels or change in ethanol and methanol levels.”

Probably not a substantial claim: may not pass S3 (load-bearing).

We also found no evidence of carry-over effect with these outcome measures.

“We also found no evidence of carry-over effect with these outcome measures.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Parents of these children reported a chronic low BMI and inability to gain weight over the span of years, likely due to self-restricted diet and low appetite in these participants.

“Parents of these children reported a chronic low BMI and inability to gain weight over the span of years, likely due to self-restricted diet and low appetite in these participants.”

May combine two claims.

Any reported gassiness occurred at the onset of supplementation and then diminished shortly thereafter with a subsequent reduction in gassiness below baseline.

“Any reported gassiness occurred at the onset of supplementation and then diminished shortly thereafter with a subsequent reduction in gassiness below baseline (Fig 5).”

May combine two claims.

Participant 208 began the study with a high Bifidobacterium enterotype, and moved to the high Prevotella enterotype with the BCP only treatment.

“Participant 208 began the study with a high Bifidobacterium enterotype, and moved to the high Prevotella enterotype with the BCP only treatment.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Participant 204 began the study with a high Prevotella enterotype, moved to the mixed enterotype with the first treatment (combination), and remained in that state for the duration of the trial.

“Participant 204 began the study with a high Prevotella enterotype, moved to the mixed enterotype with the first treatment (combination) and remained in that state for the duration of the trial.”

May combine two claims.

Both ethanol and methanol levels were significantly reduced (p = 0.0256 for both) after treatment.

“Both ethanol and methanol levels were significantly reduced (p = 0.0256 for both) after treatment.”

May combine two claims.

Participant 210 began the study with a high Bacteroides enterotype, moved to the high Bifidobacterium enterotype with the BCP only treatment, returned to the high Bacteroides enterotype after the washout period, and remained in that enterotype with the combination treatment.

“Participant 210 began the study with a high Bacteroides enterotype, moved to the high Bifidobacterium enterotype with the BCP only treatment, returned to the high Bacteroides enterotype after the washout period and remained in that enterotype with the combination treatment.”

May combine two claims.

All three samples in the 'mixed' community were from the same participant (204), with one sample higher in Akkermansia, one sample higher in Collinsela, and one sample moderately high in both Prevotella and Bacteroides.

“All three samples in the “mixed” community were from the same participant (204) with one of the samples higher in Akkermansia, one sample higher in Collinsela, and one sample moderately high in both Prevotella and Bacteroides.”

May combine two claims.

Participant 211 was in the high Prevotella enterotype at the start of each treatment period; both the BCP only and combination treatment moved this participant into the high Bifidobacterium enterotype.

“Participant 211 was in the high Prevotella enterotype at the start of each treatment period; both the BCP only and combination treatment moved this participant into the high Bifidobacterium enterotype.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The fecal and urinary metabolomes of each individual tended to cluster together more tightly than the plasma metabolome.

“The fecal and urinary metabolomes of each individual tended to cluster together more tightly than the plasma metabolome.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Many parents reported that their children were sensitive to the taste of the supplement.

“as many parents reported that their children were sensitive to the taste of the supplement.”

May combine two claims.

Bovine colostrum product is well tolerated in children with ASD and GI symptoms, both as its own treatment and when combined with the probiotic B. infantis.

“the results confirm that the supplement is well tolerated”

• Also stated in: § Conclusions · hedged

  “Bovine colostrum product appears to be well-tolerated in these children as its own treatment as well as when combined with the probiotic B. infantis.”

Classified as probably not a substantial claim. May combine two claims.

Oligosaccharides, the third most abundant component of human milk, serve to selectively promote the growth of bifidobacteria in the gut while providing limited nutritional support to the infant directly.

“Interestingly, oligosaccharides, the third most abundant component of human milk, serve to selectively promote the growth of bifidobacteria in the gut while providing limited nutritional support to the infant directly [27–29].”

• cites [27] D Garrido, 2012, A molecular basis for bifidobacterial enrichment in the infant gastrointestinal tract, Advances in nutrition (Bethesda, Md) sourceNot checked yet

  Not checked in the free run.

• cites [28] DA Sela, 2010, Nursing our microbiota: molecular linkages between bifidobacteria and milk oligosaccharides, Trends in microbiology sourceNot checked yet

  Not checked in the free run.

• cites [29] JT Smilowitz, 2014, Breast milk oligosaccharides: structure-function relationships in the neonate, Annual review of nutrition sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Most studies demonstrate that children with ASD have more bacterial diversity and lower overall abundance of potentially beneficial taxa such as Bifidobacterium and Akkermansia.

“Most studies demonstrate that children with ASD have more bacterial diversity [10, 14] and possess lower overall abundance of potentially beneficial taxa, such as Bifidobacterium and Akkermansia, [5, 10, 11], although some populations appear to differ from this trend [10, 13].”

• cites [10] SM Finegold, 2010, Pyrosequencing study of fecal microflora of autistic and control children, Anaerobe sourceNot checked yet

  Not checked in the free run.

• cites [14] M De Angelis, 2013, Fecal Microbiota and Metabolome of Children with Autism and Pervasive Developmental Disorder Not Otherwise Specified, PloS one sourceNot checked yet

  Not checked in the free run.

• cites [5] L Wang, 2011, Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism, Applied and environmental microbiology sourceNot checked yet

  Not checked in the free run.

• cites [11] JB Adams, 2011, Gastrointestinal flora and gastrointestinal status in children with autism—comparisons to typical children and correlation with autism severity, BMC gastroenterology sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Children with ASD and gastrointestinal symptoms present with immune imbalances in the gut that could be associated with abnormal host responses to microbial dysbiosis and impaired gut barrier integrity.

“Furthermore, children with ASD and gastrointestinal symptoms also present with immune imbalances in the gut that could be associated with abnormal host responses to microbial dysbiosis and impaired gut barrier integrity [16–19].”

• cites [16] P D'Eufemia, 1996, Abnormal intestinal permeability in children with autism, Acta paediatrica (Oslo, Norway: 1992) sourceNot checked yet

  Not checked in the free run.

• cites [17] L de Magistris, 2010, Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives, Journal of pediatric gastroenterology and nutrition sourceNot checked yet

  Not checked in the free run.

• cites [18] P Ashwood, 2003, Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology, Journal of clinical immunology sourceNot checked yet

  Not checked in the free run.

• cites [19] MR Sanctuary, 2018, Dietary Considerations in Autism Spectrum Disorders: The Potential Role of Protein Digestion and Microbial Putrefaction in the Gut-Brain Axis, Frontiers in nutrition sourceNot checked yet

  Not checked in the free run.

May combine two claims.

B. infantis has been shown in vitro to improve gut barrier integrity and reduce expression of inflammatory genes in intestinal epithelial cells.

“It has also been shown in vitro to improve gut barrier integrity [33] and reduce expression of inflammatory genes in intestinal epithelial cells [34].”

• cites [33] M Chichlowski, 2012, Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function, Journal of pediatric gastroenterology and nutrition sourceNot checked yet

  Not checked in the free run.

• cites [34] S Wickramasinghe, 2015, Bifidobacteria grown on human milk oligosaccharides downregulate the expression of inflammation-related genes in Caco-2 cells, BMC Microbiol sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

These cytokine profiles may reflect abnormal responses to bacteria or food antigens.

“These cytokine profiles may reflect abnormal responses to bacteria or food antigens.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The prevalence of GI symptoms is four times greater in children with ASD than in children without ASD.

“An estimated 50% or more of these children are affected with the prevalence of symptoms four times greater than in children without ASD [4].”

• cites [4] BO McElhanon, 2014, Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis, Pediatrics sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The most commonly reported GI symptoms in children with ASD include chronic constipation, diarrhea, and abdominal pain.

“The most commonly reported symptoms include chronic constipation, diarrhea, and abdominal pain [4–6].”

• cites [4] BO McElhanon, 2014, Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis, Pediatrics sourceNot checked yet

  Not checked in the free run.

• cites [5] L Wang, 2011, Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism, Applied and environmental microbiology sourceNot checked yet

  Not checked in the free run.

• cites [6] T Buie, 2010, Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report, Pediatrics sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The degree of GI microbial dysbiosis has been correlated with both GI symptoms and ASD symptom severity.

“The severity of these symptoms has been correlated with the degree of GI microbial dysbiosis.”

• Also stated in: § Introduction · plain

  “The degree of this dysbiosis has been correlated with both GI symptoms [9] and ASD symptom severity [11].”

• cites [9] HM Parracho, 2005, Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children, Journal of medical microbiology sourceNot checked yet

  Not checked in the free run.

• cites [11] JB Adams, 2011, Gastrointestinal flora and gastrointestinal status in children with autism—comparisons to typical children and correlation with autism severity, BMC gastroenterology sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Over half of children with autism spectrum disorders (ASD) have gastrointestinal (GI) co-morbidities including chronic constipation, diarrhea, and irritable bowel syndrome.

“Over half of all children with autism spectrum disorders (ASD) have gastrointestinal (GI) co-morbidities including chronic constipation, diarrhea, and irritable bowel syndrome.”

• Also stated in: § Introduction · hedged

  “An estimated 50% or more of these children are affected with the prevalence of symptoms four times greater than in children without ASD [4].”

• cites [4] BO McElhanon, 2014, Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis, Pediatrics sourceNot checked yet

  Not checked in the free run.

May combine two claims.

Interventions aimed at resolving intestinal dysbiosis could help reduce the frequency and severity of GI symptoms in children with ASD and may also help balance the immune system and potentially improve certain behavioral symptoms.

“Therefore, interventions aimed at resolving intestinal dysbiosis could not only help to reduce the frequency and severity of GI symptoms in children with ASD but may also help balance the immune system and potentially improve certain behavioral symptoms as well [24].”

• cites [24] DW Kang, 2017, Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open label study, Microbiome sourceNot checked yet

  Not checked in the free run.

May combine two claims.

An abnormal ratio of Firmicutes to Bacteroidetes and increased levels of certain detrimental taxa such as Proteobacteria have been observed in children with ASD.

“Further, an abnormal ratio of Firmicutes to Bacteroidetes [12] has been observed as well as increased levels of certain detrimental taxa, such as Proteobacteria [10, 12].”

• cites [12] BL Williams, 2011, Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances, PloS one sourceNot checked yet

  Not checked in the free run.

• cites [10] SM Finegold, 2010, Pyrosequencing study of fecal microflora of autistic and control children, Anaerobe sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim. May combine two claims.

Bifidobacterium longum subsp. infantis (B. infantis) dominates the guts of healthy breastfed infants and is associated with numerous beneficial health outcomes.

“It has been found to dominate the guts of healthy breastfed infants [30] and thus is associated with numerous beneficial health outcomes [31, 32].”

• cites [30] H Yoshioka, 1983, Development and differences of intestinal flora in the neonatal period in breast-fed and bottle-fed infants, Pediatrics sourceNot checked yet

  Not checked in the free run.

• cites [31] B Lonnerdal, 2016, Bioactive Proteins in Human Milk: Health, Nutrition, and Implications for Infant Formulas, The Journal of pediatrics sourceNot checked yet

  Not checked in the free run.

• cites [32] A O'Sullivan, 2015, The Influence of Early Infant-Feeding Practices on the Intestinal Microbiome and Body Composition in Infants, Nutrition and metabolic insightsNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Suboptimal breastfeeding practices, including non-intake of colostrum and short duration of breastfeeding, have been shown to be associated with ASD.

“In addition, suboptimal breastfeeding practices, including non-intake of colostrum and short duration of breastfeeding, have also been shown to be associated with ASD [26].”

• cites [26] YM Al-Farsi, 2012, Effect of suboptimal breast-feeding on occurrence of autism: a case-control study, Nutrition (Burbank, Los Angeles County, Calif) sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Children with ASD have been reported to generally consume less than 50% of the daily recommended intake of fiber.

“Children with ASD have been reported to generally consume <50% of the daily recommended intake of fiber [25].”

• cites [25] DW Lockner, 2008, Dietary intake and parents&apos; perception of mealtime behaviors in preschool-age children with autism spectrum disorder and in typically developing children, J Am Diet Assoc sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

Many reports show that children with ASD have higher counts of potentially pathogenic Clostridia than typically developing children.

“Many reports show that children with ASD have higher counts of potentially pathogenic Clostridia than typically developing children [7–10, 12], although this is not universally true [13].”

• cites [7] SM Finegold, 2002, Gastrointestinal microflora studies in late-onset autism., Clinical infectious diseases: an official publication of the Infectious Diseases Society of America sourceNot checked yet

  Not checked in the free run.

• cites [8] Y Song, 2004, Real-time PCR quantitation of clostridia in feces of autistic children, Applied and environmental microbiology sourceNot checked yet

  Not checked in the free run.

• cites [9] HM Parracho, 2005, Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children, Journal of medical microbiology sourceNot checked yet

  Not checked in the free run.

• cites [10] SM Finegold, 2010, Pyrosequencing study of fecal microflora of autistic and control children, Anaerobe sourceNot checked yet

  Not checked in the free run.

• cites [12] BL Williams, 2011, Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances, PloS one sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The study protocol received ethical approval from the Institutional Review Board of the University of California at Davis and was registered on ClinicalTrials.gov (NCT02086110).

“This study protocol received ethical approval from the Institutional Review Board of the University of California at Davis (Approval#: 450072) on 6/16/2013. The authors confirm that all ongoing and related trials for this drug/intervention are registered and this trial was registered on ClinicalTrials.gov Identifier: NCT02086110.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Written informed consent was obtained from all parents/guardians prior to study enrollment.

“Participants were provided with a complete description of the study and written informed consent was obtained from all parents/guardians prior to study enrollment.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

One participant (208) failed to provide a stool sample after the wash out period, so this participant's microbiota and fecal metabolomics data were not included for the second arm.

“One participant (208) failed to provide a stool sample after the wash out period so this participant’s microbiota and fecal metabolomics data were not included for the second arm of the study.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

One participant failed to provide blood samples due to excessive anxiety and restlessness during venipuncture, so his data was not included in the blood cytokine or metabolomics data.

“One participant also failed to provide blood samples due to excessive anxiety and restlessness during the venipuncture procedure so his data was not included in the blood cytokine or metabolomics data.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Gut microbiome enterotypes can be affected by diet and can change within the same individual.

“It has also been shown that gut microbiome enterotypes can be affected by diet and can change within the same individual [71, 72].”

• cites [71] PI Costea, 2018, Enterotypes in the landscape of gut microbial community composition, Nature microbiology sourceNot checked yet

  Not checked in the free run.

• cites [72] AL Hicks, 2018, Gut microbiomes of wild great apes fluctuate seasonally in response to diet, Nat Commun sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Of the participants included in the final analysis, four received the combination supplementation first and four received the BCP only supplementation first.

“Of the participants included in the final analysis, four received the combination supplementation first while four received the BCP only supplementation first.”

May combine two claims.

Bovine colostrum contains a limited amount of milk oligosaccharides that may serve as a selective food source (prebiotic) and promote the growth of B. infantis.

“Bovine colostrum not only contains a limited amount of milk oligosaccharides that may serve as a selective food source (prebiotic) and promote the growth of this particular bacteria [35, 36], but also contains an abundance of immune proteins, such as immunoglobulins, lactoferrin and numerous cytokines.”

• cites [35] DC Dallas, 2014, Comprehensive peptidomic and glycomic evaluation reveals that sweet whey permeate from colostrum is a source of milk protein-derived peptides and oligosaccharides, Food research international (Ottawa, Ont) sourceNot checked yet

  Not checked in the free run.

• cites [36] DL Aldredge, 2013, Annotation and structural elucidation of bovine milk oligosaccharides and determination of novel fucosylated structures, Glycobiology sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

All participants (n = 11) were randomly assigned to receive either BCP only or the combination (BCP + Bifidobacterium infantis) during the first or second arm of the study.

“All participants (n = 11) were randomly assigned to receive either the BCP only or the combination (BCP + Bifidobacterium infantis) during the first or second arm of the study.”

Classified as probably not a substantial claim. May combine two claims.

Randomization was performed by the Investigational Drug Service at UC Davis Medical Center so that all study personnel and participants were blinded as to the order of treatment.

“Randomization was performed by the Investigational Drug Service (IDS) at the UC Davis Medical Center so that all study personnel and participants were blinded as to the order of treatment.”

May combine two claims.

Many children on the autism spectrum have sensory sensitivities resulting in restricted and selective diets which can often make oral administration of medications or supplements challenging.

“Many children on the autism spectrum have sensory sensitivities resulting in restricted and selective diets [47] which can often make oral administration of medications or supplements challenging.”

• cites [47] SA Cermak, 2010, Food selectivity and sensory sensitivity in children with autism spectrum disorders, Journal of the Academy of Nutrition and DieteticsNot checked yet

  Not checked in the free run.

May combine two claims.

The parentally-reported dosing diaries were more accurate than assessing returned supplement because the study supplement was often all mixed into a food item but was incompletely consumed thereafter.

“These data were more accurate than assessing returned supplement as the study supplement was often all mixed into a food item but was incompletely consumed thereafter.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Data were received from all study participants so that all eligible participants were included in the analysis (n = 8).

“Data were received from all study participants so that all eligible participants were included in the analysis (n = 8).”

Classified as probably not a substantial claim. May combine two claims.

Both treatments were provided in powder form with identical taste and texture to preserve the blinding of the study.

“Both treatments were provided in powder form with identical taste and texture to preserve the blinding of the study.”

Classified as probably not a substantial claim.

An analysis of ten participants allows for 80% power to detect differences of magnitude 1.94 RMSE, under two-sided testing (α = 0.05) of the null hypothesis that the effect size is 0.

“An analysis of ten participants allows for 80% power to detect differences of magnitude 1.94 RMSE, under two-sided testing (α = 0.05) of the null hypothesis that the effect size is 0.”

Classified as probably not a substantial claim.

It is possible to classify microbiomes by groups of microbial communities or enterotypes, each of which is often dominated by a particular organism.

“It is possible to classify microbiomes by groups of microbial communities or enterotypes, each of which is often dominated by a particular organism [69, 70].”

• cites [69] M Arumugam, 2011, Enterotypes of the human gut microbiome, Nature sourceNot checked yet

  Not checked in the free run.

• cites [70] J Ravel, 2011, Vaginal microbiome of reproductive-age women, Proceedings of the National Academy of Sciences of the United States of America sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Concurrent supplementation with both the probiotic B. infantis and bovine colostrum product (BCP) as a source of immune factors and prebiotic glycans could alter the microbiota to a more beneficial composition in order to improve gut health in children with ASD and GI symptoms.

“Therefore, concurrent supplementation with both the probiotic B. infantis and bovine colostrum product (BCP) as a source of immune factors and prebiotic glycans could alter the microbiota to a more beneficial composition in order to improve gut health in children with ASD and GI symptoms.”

Classified as probably not a substantial claim. May combine two claims.

Each participant received both treatments, but was randomized as to the order of treatment.

“Each participant received both treatments, but were randomized as to the order of treatment.”

May combine two claims.

These immune proteins have been shown to resist digestion in order to be biologically active in the gut and can further modulate the microbiota and the immune system.

“These proteins have been shown to resist digestion [37, 38] in order to be biologically active in the gut [39] and can further modulate the microbiota [40] and the immune system [40–42].”

• cites [37] B Lonnerdal, 2011, Bovine lactoferrin can be taken up by the human intestinal lactoferrin receptor and exert bioactivities, Journal of pediatric gastroenterology and nutrition sourceNot checked yet

  Not checked in the free run.

• cites [38] RD Brines, 1983, The effect of trypsin and chymotrypsin on the in vitro antimicrobial and iron-binding properties of lactoferrin in human milk and bovine colostrum. Unusual resistance of human apolactoferrin to proteolytic digestion, Biochimica et biophysica acta sourceNot checked yet

  Not checked in the free run.

• cites [39] JB German, 2002, Bioactive components in milk, Current opinion in clinical nutrition and metabolic care sourceNot checked yet

  Not checked in the free run.

• cites [40] HJ Brooks, 2006, Potential prophylactic value of bovine colostrum in necrotizing enterocolitis in neonates: an in vitro study on bacterial attachment, antibody levels and cytokine production, FEMS immunology and medical microbiology sourceNot checked yet

  Not checked in the free run.

• cites [41] E Satyaraj, 2013, Supplementation of diets with bovine colostrum influences immune function in dogs, Br J Nutr sourceNot checked yet

  Not checked in the free run.

• cites [42] C Boudry, 2007, Effects of oral supplementation with bovine colostrum on the immune system of weaned piglets, Research in veterinary science sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Eleven children with ASD and gastrointestinal symptoms met initial study criteria and were randomly assigned to receive the combination or BCP supplementation first.

“Eleven children met initial study criteria, all of which were randomly assigned to receive the combination or BCP supplementation first (Fig 1).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Nine participants completed the study, but eight were included in the final analysis.

“While nine participants completed the study, eight were included in the final analysis.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

Improvement may be explained by a reduction in IL-13 and TNF-α production in some participants.

“Improvement may be explained by a reduction in IL-13 and TNF-α production in some participants.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Two participants exited the study during the first arm due to time constraints or other family medical issues.

“Two participants exited the study during the first arm due to time constraints (n = 1) and other family medical issues (n = 1).”

Probably not a substantial claim: may not pass S3 (load-bearing).

One participant was excluded from the analysis due to a post-trial diagnosis of celiac disease.

“One participant was excluded from the analysis due to a post-trial diagnosis of celiac disease.”

Classified as probably not a substantial claim.

The study was a double-blind, crossover, randomized clinical trial.

“The study was a double-blind, crossover, randomized clinical trial (RCT) conducted at the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute and University of California Davis Medical Center, Sacramento, California, from 6/6/14 to 11/16/15.”

May combine two claims.

Many of these immune proteins are heavily glycosylated, which may also provide a prebiotic effect as these sugars can be cleaved by bacterial glycosidases.

“In addition, many of these immune proteins are heavily glycosylated [43, 44], which may also provide a prebiotic effect as these sugars can be cleaved by bacterial glycosidases [45, 46].”

• cites [43] CC Nwosu, 2012, Comparison of the human and bovine milk N-glycome via high-performance microfluidic chip liquid chromatography and tandem mass spectrometry, J Proteome Res sourceNot checked yet

  Not checked in the free run.

• cites [44] X Dong, 2016, LC-MS/MS analysis of permethylated free oligosaccharides and N-glycans derived from human, bovine, and goat milk samples, Electrophoresis sourceNot checked yet

  Not checked in the free run.

• cites [45] D Garrido, 2012, Endo-beta-N-acetylglucosaminidases from infant gut-associated bifidobacteria release complex N-glycans from human milk glycoproteins, Molecular & cellular proteomics: MCP sourceNot checked yet

  Not checked in the free run.

• cites [46] S Karav, 2016, Oligosaccharides Released from Milk Glycoproteins Are Selective Growth Substrates for Infant-Associated Bifidobacteria, Applied and environmental microbiology sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The absence of an increase in Bifidobacterium at any taxonomic level might indicate that decreases in non-B. infantis Bifidobacterium are occurring concurrently with increases in B. infantis and our analysis is not specific enough to quantify these changes.

“The absence of an increase in Bifidobacterium at any taxonomic level might indicate that decreases in non-B. infantis Bifidobacterium are occurring concurrently with increases in B. infantis and our analysis is not specific enough to quantify these changes.”

May combine two claims.

Early antibiotic exposure perturbs the gut microbiota, leading to dysbiosis and gastrointestinal problems.

“Early antibiotic exposure, due in part to this population’s increased incidence of ear infections [73], is also associated with ASD [74] and perturbs the gut microbiota [9], leading to dysbiosis and gastrointestinal problems.”

• cites [9] HM Parracho, 2005, Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children, Journal of medical microbiology sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

A substantial number of children with ASD experience chronic gastrointestinal symptoms including constipation, diarrhea, pain associated with bowel movements and gassiness/bloating.

“A substantial number of children with ASD experience chronic gastrointestinal symptoms including constipation, diarrhea, pain associated with bowel movements and gassiness/bloating [6].”

• cites [6] T Buie, 2010, Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report, Pediatrics sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

This effect may actually be beneficial considering that these same participants had low initial BMI.

“However, this effect may actually be beneficial considering that these same participants had low initial BMI.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Akkermansia species, including Akkermansia muciniphila, have been found to be reduced in children with ASD compared to typically developing children.

“Akkermansia species, including Akkermansia muciniphila, have been found to be reduced in children with ASD compared to typically developing children [5].”

• cites [5] L Wang, 2011, Low relative abundances of the mucolytic bacterium Akkermansia muciniphila and Bifidobacterium spp. in feces of children with autism, Applied and environmental microbiology sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

It is also possible that B. infantis did not colonize at a detectable level.

“It is also possible that B. infantis did not colonize at a detectable level.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

It is also possible that lack of changes to the microbiota community status indicates lack of efficacy of the supplement and the reduction in certain GI symptoms may be due to other factors, such as a placebo effect.

“Finally, it is also possible that lack of changes to the microbiota community status indicates lack of efficacy of the supplement and the reduction in certain GI symptoms may be due to other factors, such as a placebo effect.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

This increased appetite and consumption of novel foods may be due to reduced abdominal pain or improved stool evacuation and might partially explain the weight gain experienced by some of these children.

“This increased appetite and consumption of novel foods may be due to reduced abdominal pain or improved stool evacuation and might partially explain the weight gain experienced by some of these children.”

May combine two claims.

The finding that parents reported greater improvement on the BCP only arm is likely reliable because all participants and parents were blinded as to the order of treatment and there was no apparent difference in taste or texture between the supplements.

“This finding is important and likely reliable as all participants and parents were blinded as to the order of treatment and there was no apparent difference in taste or texture between the supplements.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Early antibiotic exposure is associated with ASD.

“Early antibiotic exposure, due in part to this population’s increased incidence of ear infections [73], is also associated with ASD [74] and perturbs the gut microbiota [9], leading to dysbiosis and gastrointestinal problems.”

• cites [74] R Niehus, 2006, Early medical history of children with autism spectrum disorders, Journal of developmental and behavioral pediatrics: JDBP sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The incidence of these symptoms may be due in part to the presence of an abnormal microbiota as well as aberrant immune function in the GI tracts of these children.

“The incidence of these symptoms may be due in part to the presence of an abnormal microbiota as well as aberrant immune function in the GI tracts of these children [11, 15, 18].”

• cites [11] JB Adams, 2011, Gastrointestinal flora and gastrointestinal status in children with autism—comparisons to typical children and correlation with autism severity, BMC gastroenterology sourceNot checked yet

  Not checked in the free run.

• cites [15] RN Nikolov, 2009, Gastrointestinal symptoms in a sample of children with pervasive developmental disorders, Journal of autism and developmental disorders sourceNot checked yet

  Not checked in the free run.

• cites [18] P Ashwood, 2003, Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology, Journal of clinical immunology sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The gut microbiota of participant 204 was unstable, so results from this individual must be interpreted with caution.

“However, it is clear that the gut microbiota of this individual was unstable and so results must be interpreted with caution.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The gut microbiome is stable and adult-like at age 3.

“Our youngest study participant was 3 years of age and the gut microbiome is stable and adult-like at this age [76].”

• cites [76] T Yatsunenko, 2012, Human gut microbiome viewed across age and geography, Nature sourceNot checked yet

  Not checked in the free run.

May combine two claims.

In summary, the treatments appeared to have either no effect or an inconsistent effect on enterotype.

“In summary, the treatments appeared to have either no effect or an inconsistent effect on enterotype.”

Probably not a substantial claim: may not pass S3 (load-bearing).

This side effect has been reported in other studies of prebiotic supplementation as well.

“This side effect has been reported in other studies of prebiotic supplementation as well [75].”

• cites [75] O Goetze, 2008, Effect of a prebiotic mixture on intestinal comfort and general wellbeing in health, Br J Nutr sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

While the study supplement appeared to be well tolerated in the current cohort, many children with ASD report sensitivity to dairy products and thus this supplement may not be appropriate for all children with ASD and GI symptoms.

“However, it is important to note that while the study supplement appeared to be well tolerated in the current cohort, many children with ASD report sensitivity to dairy products and thus this supplement may not be appropriate for all children with ASD and GI symptoms.”

• AssumptionRests on an assumption: Many children with ASD report sensitivity to dairy products.

Probably not a substantial claim: may not pass S3 (load-bearing).

While species-level composition was not determined for this analysis, higher levels of mucus-degrading bacteria may suggest improvement in GI barrier function in this subject.

“While species-level composition was not determined for this analysis, higher levels of mucus-degrading bacteria may suggest improvement in GI barrier function in this subject.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Other studies have shown that Akkermansia levels are higher in children with ASD compared to typically developing children, although species-level composition was not examined.

“However, other studies have shown that Akkermansia levels are higher in children with ASD compared to typically developing children, although species-level composition was not examined [13].”

• cites [13] DW Kang, 2013, Reduced incidence of Prevotella and other fermenters in intestinal microflora of autistic children, PloS one sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

The lack of global changes in metabolite profile could indicate lack of efficacy of the study supplement.

“Lack of global changes in metabolite profile may be due to small sample size or could indicate lack of efficacy of the study supplement so that reduction in GI symptoms may be due to other factors, such as a placebo effect.”

May combine two claims.

Our results are in agreement with previous findings of elevated TNF-α expression in children with ASD and GI symptoms compared to non-inflamed controls that was similar to participants with Crohn's disease.

“Our results are in agreement with previous findings of elevated TNF-α expression in children with ASD and GI symptoms [87] compared to non-inflamed controls that was similar to participants with Crohn’s disease [22].”

• cites [87] H Jyonouchi, 2005, Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention, Neuropsychobiology sourceNot checked yet

  Not checked in the free run.

• cites [22] P Ashwood, 2006, Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms, Journal of neuroimmunology sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Reduction in GI symptoms may be due to other factors, such as a placebo effect.

“Lack of global changes in metabolite profile may be due to small sample size or could indicate lack of efficacy of the study supplement so that reduction in GI symptoms may be due to other factors, such as a placebo effect.”

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

Children with ASD and gastrointestinal symptoms tend to experience gut immune dysfunction and bacterial dysbiosis.

“Children with ASD and gastrointestinal symptoms tend to experience gut immune dysfunction and bacterial dysbiosis.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The heterogeneity of the sample population in terms of gastrointestinal symptoms makes assessing improvement difficult.

“In addition, the heterogeneity of our sample population in terms of gastrointestinal symptoms makes assessing improvement difficult.”

May combine two claims.

The abundance of outcomes based on parental reporting is a limitation, but was necessary due to the lack of more objective measures of gastrointestinal symptoms and behavior changes.

“In addition, the abundance of outcomes based on parental reporting is another limitation to this study, but was also necessary due to the lack of more objective measures of gastrointestinal symptoms and behavior changes.”

• AssumptionRests on an assumption: There is a lack of more objective measures of gastrointestinal symptoms and behavior changes.

May combine two claims.

Improvements in gastrointestinal symptoms may also be due to simple growth and maturation, but the chronic nature of these symptoms and the report of return of symptoms upon post-study follow up with parents suggest that this may not be the case.

“While improvements in gastrointestinal symptoms may also be due to simple growth and maturation, the chronic nature of these symptoms and the report of return of symptoms upon post-study follow up with parents suggest that this may not be the case.”

• AssumptionRests on an assumption: Symptoms returned upon post-study follow up with parents.
• AssumptionRests on an assumption: The GI symptoms were chronic.

May combine two claims.

Reduction in inflammatory cytotoxic T lymphocytes is concordant with clinical outcomes and suggests that bovine colostrum may have helped to improve GI function through reduction of expression of pro-inflammatory cytokines in the gut.

“The reduction in inflammatory cytotoxic T lymphocytes is concordant with clinical outcomes and suggests that bovine colostrum may have helped to improve GI function through reduction of expression of pro-inflammatory cytokines in the gut.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Others report the opposite, with constipation reported 2-3 times more frequently than diarrhea.

“However, others report the opposite, with constipation reported 2–3 times more frequently than diarrhea [96, 97]”

• cites [96] B Taylor, 2002, Measles, mumps, and rubella vaccination and bowel problems or developmental regression in children with autism: population study, BMJ (Clinical research ed) sourceNot checked yet

  Not checked in the free run.

• cites [97] E Fombonne, 2001, No evidence for a new variant of measles-mumps-rubella-induced autism, Pediatrics sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The trend toward greater symptom reduction with BCP only treatment was marginal, and high variability in participant response makes it difficult to conclude that BCP demonstrated greater symptom reduction than the combination treatment.

“The trend toward greater symptom reduction with BCP only treatment was marginal and it is difficult to conclude that the BCP supplement demonstrated greater symptom reduction than the combination treatment due to high variability in response of our participants.”

May combine two claims.

All participants were receiving standard of care treatments for ASD, and there were no changes in these services during the course of the study.

“Similarly, all of our participants were receiving standard of care treatments for ASD, and there were no changes in these services during the course of the study.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Recent studies have shown that children with ASD test positive for anti-Candida immunoglobulins at a higher rate compared to typically developing children.

“Recent studies have shown that children with ASD test positive for anti-Candida immunoglobulins at a higher rate compared to typically developing children [81].”

• cites [81] HK Hughes, 2018, Anti-Candida albicans IgG Antibodies in Children With Autism Spectrum Disorders, Frontiers in Psychiatry sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The prevalence of gastrointestinal yeast infections in children with ASD and GI symptoms has been documented.

“Indeed, the prevalence of gastrointestinal yeast infections in children with ASD and GI symptoms has been documented [85].”

• cites [85] MR Iovene, 2016, Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders, MycopathologiaNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

High ethanol levels have also been found in the blood in patients with extreme cases of Crohn's disease and short gut.

“High ethanol levels have also been found in the blood in patients with extreme cases of Crohn’s disease [82] and short gut [83, 84].”

• cites [82] BT Welch, 2016, Auto-brewery Syndrome in the Setting of Long-standing Crohn&apos;s Disease: A Case Report and Review of the Literature, Journal of Crohn's & colitisNot checked yet

  Not checked in the free run.

• cites [83] A Dahshan, 2001, Auto-brewery syndrome in a child with short gut syndrome: case report and review of the literature, Journal of pediatric gastroenterology and nutrition sourceNot checked yet

  Not checked in the free run.

• cites [84] E Jansson-Nettelbladt, 2006, Endogenous ethanol fermentation in a child with short bowel syndrome, Acta paediatrica (Oslo, Norway: 1992) sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

There is a wide range in the reported prevalence of GI conditions in ASD, ranging from 9-70%, and estimating the true prevalence from existing studies is difficult due to referral and ascertainment bias.

“There is a wide range in the reported prevalence of GI conditions in ASD, ranging from 9–70% [6], and estimating the true prevalence from existing studies is difficult due to referral and ascertainment bias [6].”

• cites [6] T Buie, 2010, Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report, Pediatrics sourceNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

The lack of global changes in metabolite profile may be due to small sample size.

“Lack of global changes in metabolite profile may be due to small sample size or could indicate lack of efficacy of the study supplement so that reduction in GI symptoms may be due to other factors, such as a placebo effect.”

May combine two claims.

Our findings do not support preliminary in vitro data and suggest that consumption of raw bovine colostrum product may be effective at reducing pro-inflammatory cytokine production in the gut.

“Our findings do not support this preliminary in vitro data and suggest that consumption of raw bovine colostrum product may be effective at reducing pro-inflammatory cytokine production in the gut.”

• cites [88] H Jyonouchi, 2002, Innate Immunity Associated with Inflammatory Responses and Cytokine Production against Common Dietary Proteins in Patients with Autism Spectrum Disorder, Neuropsychobiology sourceNot checked yet

  Not checked in the free run.

• cites [89] H Jyonouchi, 2005, Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders, The Journal of pediatrics sourceNot checked yet

  Not checked in the free run.

May combine two claims.

High fecal ethanol levels could be indicative of yeast overgrowth that is reduced by treatment.

“While we found no evidence of high ethanol levels in the blood of our participants, high fecal levels could be indicative of yeast overgrowth that is reduced by treatment.”

• cites [79] A Hunnisett, 1990, Gut Fermentation (or the ‘Auto-brewery’) Syndrome: A New Clinical Test with Initial Observations and Discussion of Clinical and Biochemical Implications, Journal of Nutritional Medicine sourceNot checked yet

  Not checked in the free run.

• cites [80] B Cordell, 2013, A case study of gut fermentation syndrome (auto-brewery) with Saccharomyces cerevisiae as the causative organism, International Journal of Clinical Medicine sourceNot checked yet

  Not checked in the free run.

• cites [85] MR Iovene, 2016, Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders, MycopathologiaNot checked yet

  Not checked in the free run.

Probably not a substantial claim: may not pass S3 (load-bearing).

This distribution is congruent with some studies of GI symptoms in ASD, with diarrhea occurring 1.5-2 times more than constipation.

“This is congruent with some studies of GI symptoms in ASD, with diarrhea occurring 1.5–2 times more than constipation [9, 94, 95]”

• cites [9] HM Parracho, 2005, Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children, Journal of medical microbiology sourceNot checked yet

  Not checked in the free run.

• cites [94] CA Molloy, 2003, Prevalence of chronic gastrointestinal symptoms in children with autism and autistic spectrum disorders, Autism sourceNot checked yet

  Not checked in the free run.

• cites [95] M Xue, 2008, Autism spectrum disorders: concurrent clinical disorders, Journal of child neurology sourceNot checked yet

  Not checked in the free run.

Classified as probably not a substantial claim.

Conclusions from this study are limited due to the small sample size and high heterogeneity of symptoms between participants.

“However, conclusions from this study are limited due to the small sample size and high heterogeneity of symptoms between participants.”

May combine two claims.

Bovine colostrum is generally high in immune factors that are heavily glycosylated.

“Bovine colostrum is generally high in immune factors [90] that are heavily glycosylated [91].”

• cites [90] K Stelwagen, 2009, Immune components of bovine colostrum and milk, Journal of animal science sourceNot checked yet

  Not checked in the free run.

• cites [91] S Takimori, 2011, Alteration of the N-glycome of bovine milk glycoproteins during early lactation, The FEBS journal sourceNot checked yet

  Not checked in the free run.

May combine two claims.

The study duration was short (5 weeks on each arm), and we would not expect to see much growth and maturation occurring in such a limited time.

“Moreover, our study duration was short (5 weeks on each arm), and we would not expect to see much growth and maturation occurring in such a limited time.”