Human milk oligosaccharide 2′-fucosyllactose supplementation improves gut barrier function and signaling in the vagal afferent pathway in mice

Lee, Sun Hye; Goodson, Michael L.; Vang, Wendie; Rutkowsky, Jennifer; Kalanetra, Karen M.; Bhattacharya, Mrittika; Barile, Daniela; Raybould, Helen E.

doi:10.1039/d1fo00658d

Cited by 22 publications

(26 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The absence of an effect on body weight and food intake is in line with short-term studies (6-8 weeks) that used comparably low doses of 2 -FL (1 and 2% w/v) as herein (2.5% w/w) (33). In these short-term studies only the higher doses of 2 -FL (5 and 10% w/v) decreased body weight, which was also associated with a lowering of caloric intake (33,34). In line with our findings, no major effect on plasma lipids was observed in a meta-analysis of other types of prebiotic treatments in ultrasound-or biopsy-confirmed NAFLD patients (6).…”

Section: Discussionsupporting

confidence: 73%

The Human Milk Oligosaccharide 2′-Fucosyllactose Alleviates Liver Steatosis, ER Stress and Insulin Resistance by Reducing Hepatic Diacylglycerols and Improved Gut Permeability in Obese Ldlr-/-.Leiden Mice

et al. 2022

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is a complex multifactorial disorder that is associated with gut dysbiosis, enhanced gut permeability, adiposity and insulin resistance. Prebiotics such as human milk oligosaccharide 2′-fucosyllactose are thought to primarily improve gut health and it is uncertain whether they would affect more distant organs. This study investigates whether 2′-fucosyllactose can alleviate NAFLD development in manifest obesity. Obese hyperinsulinemic Ldlr-/-.Leiden mice, after an 8 week run-in on a high-fat diet (HFD), were treated with 2′-fucosyllactose by oral gavage until week 28 and compared to HFD-vehicle controls. 2′-fucosyllactose did not affect food intake, body weight, total fat mass or plasma lipids. 2′-fucosyllactose altered the fecal microbiota composition which was paralleled by a suppression of HFD-induced gut permeability at t = 12 weeks. 2′-fucosyllactose significantly attenuated the development of NAFLD by reducing microvesicular steatosis. These hepatoprotective effects were supported by upstream regulator analyses showing that 2′-fucosyllactose activated ACOX1 (involved in lipid catabolism), while deactivating SREBF1 (involved in lipogenesis). Furthermore, 2′-fucosyllactose suppressed ATF4, ATF6, ERN1, and NUPR1 all of which participate in endoplasmic reticulum stress. 2′-fucosyllactose reduced fasting insulin concentrations and HOMA-IR, which was corroborated by decreased intrahepatic diacylglycerols. In conclusion, long-term supplementation with 2′-fucosyllactose can counteract the detrimental effects of HFD on gut dysbiosis and gut permeability and attenuates the development of liver steatosis. The observed reduction in intrahepatic diacylglycerols provides a mechanistic rationale for the improvement of hyperinsulinemia and supports the use of 2′-fucosyllactose to correct dysmetabolism and insulin resistance.

show abstract

Section: Discussionsupporting

confidence: 73%

The Human Milk Oligosaccharide 2′-Fucosyllactose Alleviates Liver Steatosis, ER Stress and Insulin Resistance by Reducing Hepatic Diacylglycerols and Improved Gut Permeability in Obese Ldlr-/-.Leiden Mice

et al. 2022

View full text Add to dashboard Cite

show abstract

“…HMOs are complex glycans [ 5 ] that withstand digestion of the upper gastrointestinal tract [ 6 , 7 ] to act as a prebiotic in the lower gastrointestinal tract [ 11 , 12 ], with physiological benefits for the infant [ 1 , 2 , 3 , 34 ]. HMO are proposed to influence intestinal development [ 8 , 9 , 10 ], as well as microbiota composition by promoting growth of Bifidobacterium species, including B. infantis [ 11 , 12 , 13 ]. Infant formulas that contain prebiotics, such as galactooligosaccharides (GOS) and fructooligosaccharides, support Bifidobacterium growth are currently commercially available [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…We hypothesized that 2’-FL and Bi-26 alone or in combination would be well tolerated and support normal piglet growth, and aimed to investigate any synergy between 2’-FL and Bi-26. Based on previous evidence [ 8 , 9 , 10 ], we further hypothesized that 2’-FL would promote intestinal development in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…In the intestine, 2’-FL dose-dependently decreased cell proliferation and increased sucrase activity in cultured cells [ 8 , 9 ], suggesting a shift towards differentiation. In vivo, dietary HMO increased cecal barrier function in mice [ 10 ]. In the colon, HMOs are metabolized by the microbiota, and some species of Bifidobacterium and Bacteroides utilize HMOs as their primary energy source [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of 2’-Fucosyllactose and Bifidobacterium longum Subspecies infantis on Growth, Organ Weights, and Intestinal Development of Piglets

et al. 2021

View full text Add to dashboard Cite

Human milk is rich in oligosaccharides that influence intestinal development and serve as prebiotics for the infant gut microbiota. Probiotics and 2’-fucosyllactose (2’-FL) added individually to infant formula have been shown to influence infant development, but less is known about the effects of their synbiotic administration. Herein, the impact of formula supplementation with 2’-fucosyllactose (2’-FL) and Bifidobacterium longum subsp. infantis Bi-26 (Bi-26), or 2’-FL + Bi-26 on weight gain, organ weights, and intestinal development in piglets was investigated. Two-day-old piglets (n = 53) were randomized in a 2 × 2 design to be fed a commercial milk replacer ad libitum without (CON) or with 1.0 g/L 2’-FL. Piglets in each diet were further randomized to receive either glycerol stock alone or Bi-26 (109 CFU) orally once daily. Body weights and food intake were monitored from postnatal day (PND) 2 to 33/34. On PND 34/35, animals were euthanized and intestine, liver and brain weights were assessed. Intestinal samples were collected for morphological analyses and measurement of disaccharidase activity. Dry matter of cecum and colon contents and Bifidobacterium longum subsp. infantis abundance by RT-PCR were also measured. All diets were well tolerated, and formula intake did not differ among the treatment groups. Daily body weights were affected by 2’-FL, Bi-26, and day, but no interaction was observed. There was a trend (p = 0.075) for greater total body weight gain in CON versus all other groups. Jejunal and ascending colon histomorphology were unaffected by treatment; however, there were main effects of 2’-FL to increase (p = 0.040) and Bi-26 to decrease (p = 0.001) ileal crypt depth. The addition of 2’-FL and/or Bi-26 to milk replacer supported piglet growth with no detrimental effects on body and organ weights, or intestinal structure and function.

show abstract

“…Consumption of HMOs during early-life, specifically 2′-FL, alters various modulators of the gut-brain axis, including lowering pro-inflammatory immune responses, increasing bifidobacteria abundance in the gut, and improving the gut barrier integrity and vagal afferent signaling ( Goehring et al, 2016 ; Cerdo et al, 2017 ; Berger B. et al, 2020 ; Lee et al, 2021 ). Additionally, numerous animal and clinical studies have demonstrated the long-term beneficial effects of 2′-FL consumption during early-life in terms of cognitive development ( Oliveros et al, 2016 ; Berger P. K. et al, 2020 ) and potential mechanisms for brain structural changes ( Vázquez et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

Influence of 2′-Fucosyllactose and Bifidobacterium longum Subspecies infantis Supplementation on Cognitive and Structural Brain Development in Young Pigs

Sutkus

Joung

Hirvonen³

et al. 2022

Front. Neurosci.

View full text Add to dashboard Cite

Development of the gut-brain axis during early-life is an important contributor of brain structural and functional development. Human milk oligosaccharides and gut microbiota have potential beneficial effects on various aspects of development; however, the effects of 2′-fucosyllactose (2′-FL) and Bifidobacterium longum subsp. infantis Bi-26 (Bi-26) administration during infancy separately and combined are still not clear. Therefore, we investigated the effects of early administration of dietary 2′-FL and Bi-26 on brain structural and functional development in the young pig. From postnatal day (PND) 2–34 or 35, fifty-two intact male pigs were randomly assigned to treatment groups in a 2 × 2 factorial arrangement and provided ad libitum access to a nutritionally adequate milk replacer without or with 1.0 g of 2′-FL/L of reconstituted liquid. Pigs within each diet group were further stratified to receive a daily oral dose of glycerol stock without or with Bi-26 (109 CFU). Pigs were subjected to the novel object recognition (NOR) task from PND 27–31 to assess recognition memory and subsequently underwent magnetic resonance imaging procedures at PND 32 or 33 to assess brain macrostructure and microstructure. Pigs that received Bi-26 had smaller absolute brain volumes for 9 of 27 brain regions of interest, and smaller relative volumes for 2 regions associated with kinesthesia (P < 0.05). Synbiotic administration of 2′-FL and Bi-26 elicited interactive effects (P < 0.05) on several microstructural brain components, where dual supplementation negated the effects of each test article alone. Behavioral outcomes indicated that pigs did not express novelty preference, regardless of treatment group, demonstrating no effects of 2′-FL and Bi-26 on recognition memory when supplemented alone or in combination. Interactive effects (P < 0.05) were observed for the number of all object visits, latency to the first object visit, and number of familiar object visits. Pigs that did not receive Bi-26 supplementation exhibited less time interacting with the familiar object in total (P = 0.002) and on average (P = 0.005). In conclusion, supplementation of 2′-FL and/or Bi-26 elicited some alterations in object exploratory behaviors and macro/micro-structures of the brain, but changes in recognition memory were not observed. Specifically in brain microstructure, synbiotic administration of 2′-FL and Bi-26 appeared to negate effects observed when each dietary article was supplemented separately.

show abstract

Human milk oligosaccharide 2′-fucosyllactose supplementation improves gut barrier function and signaling in the vagal afferent pathway in mice

Abstract: 2’-Fucosyllactose (2’-FL), a predominant human milk oligosaccharide, attenuates HF diet-induced metabolic and intestinal barrier impairment, improves gut hormone resistance, and alters the intestinal microbiota and microbiota-derived metabolites.

Cited by 22 publications

References 60 publications

The Human Milk Oligosaccharide 2′-Fucosyllactose Alleviates Liver Steatosis, ER Stress and Insulin Resistance by Reducing Hepatic Diacylglycerols and Improved Gut Permeability in Obese Ldlr-/-.Leiden Mice

The Human Milk Oligosaccharide 2′-Fucosyllactose Alleviates Liver Steatosis, ER Stress and Insulin Resistance by Reducing Hepatic Diacylglycerols and Improved Gut Permeability in Obese Ldlr-/-.Leiden Mice

Evaluation of 2’-Fucosyllactose and Bifidobacterium longum Subspecies infantis on Growth, Organ Weights, and Intestinal Development of Piglets

Influence of 2′-Fucosyllactose and Bifidobacterium longum Subspecies infantis Supplementation on Cognitive and Structural Brain Development in Young Pigs

Contact Info

Product

Resources

About