The Effect of Nutritional Intervention with Lactoferrin, Galactooligosacharides and Vitamin D on the Gut Microbiota Composition of Healthy Elderly Women.

Background: Nutritional supplements, such as bovine lactoferrin (bLF), have been studied for their immunomodulatory properties, but little is known of their effect on the gut microbiota composition of the elderly when supplemented alone or combined with other nutritional supplements such as prebiotics and micronutrients. In the present study, fecal samples from a double-blind, placebo-controlled nutritional intervention study were analysed. At baseline (T1), 25 elderly women were distributed into two groups receiving dietary intervention (n = 12) or placebo treatment (n = 13) for 9 weeks. During the first 3 weeks of the study (T2), the intervention group consumed 1 g/day bLF, followed by 3 weeks (T3) of 1 g/day bLF and 2.64 g/day active galactooligosaccharides (GOS), and 3 weeks (T4) of 1 g/day bLF, 2.64 g/day GOS and 20 µg/day of vitamin D. The placebo group received maltodextrin, in dosages matching those of the intervention group. Fecal bacterial composition was profiled using partial 16S rRNA gene amplicon sequencing. Short-chain fatty acids (SCFA) were determined in fecal water as were levels of calprotectin, zonulin, and alpha-1-antitrypsin, as markers of gastrointestinal barrier and inflammation. Results: A significant increase was observed in the relative abundance of the genus Holdemanella (p < 0.01) in the intervention group compared to the placebo at T1. During T2, Bifidobacterium relative abundance increased significantly (p < 0.01) in the intervention group compared to the placebo, and remained significantly higher until the end of the study. No other effect was reported during T3. Furthermore, concentrations of SCFAs and calprotectin, zonulin and alpha-1-antitrypsin did not change during the intervention, although zonulin levels increased significantly within the placebo group by the end of the intervention. Conclusions: We conclude that supplementation of bLF enhanced the relative abundance of Holdemanella in the fecal microbiota of healthy elderly women, and further addition of GOS enhanced the relative abundance of Bifidobacterium.

ß-Glucan-Induced Immuno-Modulation: A Role for the Intestinal Microbiota and Short-Chain Fatty Acids in Common Carp.

Dietary supplementation of fish with ß-glucans has been commonly associated with immunomodulation and generally accepted as beneficial for fish health. However, to date the exact mechanisms of immunomodulation by ß-glucan supplementation in fish have remained elusive. In mammals, a clear relation between high-fibre diets, such as those including ß-glucans, and diet-induced immunomodulation via intestinal microbiota and associated metabolites has been observed. In this study, first we describe by 16S rRNA sequencing the active naive microbiota of common carp intestine. Based on the abundance of the genus Bacteroides, well known for their capacity to degrade and ferment carbohydrates, we hypothesize that common carp intestinal microbiota could ferment dietary ß-glucans. Indeed, two different ß-glucan preparations (curdlan and MacroGard®) were both fermented in vitro, albeit with distinct fermentation dynamics and distinct production of short-chain fatty acids (SCFA). Second, we describe the potential immunomodulatory effects of the three dominant SCFAs (acetate, butyrate, and propionate) on head kidney leukocytes, showing effects on both nitric oxide production and expression of several cytokines (il-1b, il-6, tnfα, and il-10) in vitro. Interestingly, we also observed a regulation of expression of several gpr40L genes, which were recently described as putative SCFA receptors. Third, we describe how a single in vivo oral gavage of carp with MacroGard® modulated simultaneously, the expression of several pro-inflammatory genes (il-1b, il-6, tnfα), type I IFN-associated genes (tlr3.1, mx3), and three specific gpr40L genes. The in vivo observations provide indirect support to our in vitro data and the possible role of SCFAs in ß-glucan-induced immunomodulation. We discuss how ß-glucan-induced immunomodulatory effects can be explained, at least in part, by fermentation of MacroGard® by specific bacteria, part of the naive microbiota of common carp intestine, and how a subsequent production of SFCAs could possibly explain immunomodulation by ß-glucan via SCFA receptors present on leukocytes.

The Interpersonal Mindfulness Program for Health Care Professionals: a Feasibility Study.

Objectives: There are a number of mindfulness-based programs (MBPs) that have demonstrated effectiveness for patients and health care professionals. The Interpersonal Mindfulness Program (IMP) is a relatively new MBP, developed to teach those with prior mindfulness training to deepen their mindful presence, empathy and compassion in the interpersonal domain. The aim of the present study was to examine the feasibility of using the IMP with mental health care workers and assessing its effects on levels of mindfulness, self-compassion, empathy, stress and professional quality of life when compared with the control group participants. Methods: The IMP training consisted of nine weekly 2.5-h sessions and daily home practice (45-60 min). Twenty-five participants (mean age, 51.4 years) with mindfulness experience participated in the training. Twenty-two individuals in the control group (mean age, 47.5 years) were recruited from those who had followed a mindfulness training before. Feasibility of the IMP was assessed in the training participants in six domains. All study participants completed self-report questionnaires before and after the training. Results: The IMP training was considered highly acceptable and very useful. The training had a significant positive effect on self-compassion, empathy and compassion fatigue, but no effect on mindfulness, stress and compassion satisfaction. Five participants reported some mild adverse reactions. Conclusions: The IMP training appears feasible for health care professionals and seems to induce some positive effects. A few mild adverse effects were reported. Further research on the effectiveness and possible mechanisms of change of the IMP training in larger samples is needed.

Corrigendum: Sialyllactose and Galactooligosaccharides Promote Epithelial Barrier Functioning and Distinctly Modulate Microbiota Composition and Short Chain Fatty Acid Production In Vitro.

[This corrects the article DOI: 10.3389/fimmu.2019.00094.].

Sialyllactose and Galactooligosaccharides Promote Epithelial Barrier Functioning and Distinctly Modulate Microbiota Composition and Short Chain Fatty Acid Production In Vitro.

Human milk oligosaccharides (HMO) and prebiotic oligosaccharides are proposed to confer several health benefits to the infant. They shape the microbiota, have anti-inflammatory properties, and support epithelial barrier functioning. However, in order to select the best oligosaccharides for inclusion in infant formulas, there is a need to increase our understanding of the specific effects of HMO and prebiotics on the host immune system. Therefore, we investigated the effects of the HMO sialyllactose (SL), and galactooligosaccharides (GOS) on epithelial barrier functioning, microbiota composition, and SCFA production. The effect of GOS and SL on epithelial barrier functioning and microbiota composition was investigated using in vitro models. Epithelial barrier function was investigated by transcriptome analysis of fully polarized Caco-2 cells exposed for 6 h to SL or GOS. In addition, epithelial cell growth, alkaline phosphatase production, and re-epithelization was studied. Further, we investigated the effect of SL and GOS on microbiota composition and SCFA production using in vitro fecal batch cultures. Transcriptome analysis showed that SL and GOS both induced pathways that regulate cell cycle control. This gene-expression profile translated to a phenotype of halted proliferation and included the induction of alkaline phosphatase activity, a marker of epithelial cell differentiation. SL and GOS also promoted re-epithelialization in an in vitro epithelial wound repair assay. SL and GOS did show distinct modulation of microbiota composition, promoting the outgrowth of Bacteroides and bifidobacteria, respectively, which resulted in distinct changes in SCFA production profiles. Our results show that SL and GOS can both modulate epithelial barrier function by inducing differentiation and epithelial wound repair, but differentially promote the growth of specific genera in the microbiota, which is associated with differential changes in SCFA profiles.

The oligosaccharides 6'-sialyllactose, 2'-fucosyllactose or galactooligosaccharides do not directly modulate human dendritic cell differentiation or maturation.

Breast milk plays an important role in immune development in early life and protects against diseases later in life. A wide range of the beneficial effects of breast milk are attributed to human milk oligosaccharides (HMOs) as well as components such as vitamin D3 (VitD3) or TGFß. One mechanism by which HMOs might contribute to immune homeostasis and protection against disease is the induction of a local tolerogenic milieu. In this study we investigated the effect of the HMOs 6'-sialyllactose (6'SL) and 2'-fucosyllactose (2'FL) as well as prebiotic galactooligosaccharides (GOS) on DC differentiation and maturation. Isolated CD14+ monocytes were cultured for six days in the presence of GM-CSF and IL-4 with or without 6'SL, 2'FL, GOS, VitD3 or TGFß. Additionally, immature VitD3DC, TGFßDC and moDC were used as different DC types to investigate the effect of 6'SL, 2'FL and GOS on DC maturation. Surface marker expression and cytokine production was measured by flow cytometry and cytometric bead array, respectively. Unlike TGFß and vitD3, the oligosaccharides 6'SL, 2'FL and GOS did not influence DC differentiation. Next, we studied the effect of 6'SL, 2'FL and GOS on maturation of moDC, VitD3DC and TGFßDC that showed different profiles of HMO-binding receptors. 6'SL, 2'FL and GOS did not modulate LPS-induced maturation, even though their putative receptors were present on the different DCs types. Thus, whereas VitD3 and TGFß halt DC differentiation, which results in phenotypically distinct tolerogenic DCs, 6'SL, 2'FL and GOS do not alter DC differentiation or maturation of in vitro differentiated DC types.

Bovine Lactoferrin Modulates Dendritic Cell Differentiation and Function.

Lactoferrin is an abundant glycoprotein in bovine milk that has immunomodulatory effects on human cells. Bovine lactoferrin (LF) binds lipopolysaccharides (LPS) with high affinity and is postulated to act via TLR4-dependent and -independent mechanisms. It has been shown that LF modulates differentiation of human monocytes into tolerogenic dendritic cells. However, in a previous study, we showed that LPS also mediates differentiation into tolerogenic dendritic cells (DC). Since LF binds LPS with high affinity, it remains to be investigated whether LF or LPS is mediating these effects. We, therefore, further investigated the LPS-independent effect of LF on differentiation of human monocytes into dendritic cells (DC). Human monocytes were isolated by magnetic cell sorting from freshly isolated PBMCs and cultured for six days in the presence of IL-4 and GM-CSF with or without LF or proteinase K treated LF to generate DC. These immature DC were stimulated for 48 h with LPS or Poly I:C + R848. Cell surface marker expression and cytokine production were measured by flow cytometry. DC differentiated in the presence of LF produced higher IL-6 and IL-8 levels during differentiation and showed a lower expression of CD1a and HLA-DR. These LFDCs showed to be hyporesponsive towards TLR ligands as shown by their semi-mature phenotype and reduced cytokine production. The effect of LF was abrogated by proteinase K treatment, showing that the functional effects of LF were not mediated by LPS contamination. Thus, LF alters DC differentiation and dampens responsiveness towards TLR ligands. This study indicates that LF can play a role in immune homeostasis in the human GI tract.

The Co-creation and Feasibility of a Compassion Training as a Follow-up to Mindfulness-Based Cognitive Therapy in Patients with Recurrent Depression.

The aim of this study was to assess the feasibility, acceptability and preliminary effectiveness of Mindfulness - Based Compassionate Living (MBCL) as a follow-up intervention to Mindfulness Based Cognitive Therapy in adults with recurrent depression. We conducted an uncontrolled study in 17 patients with recurrent depression, in two successive groups. The first group contained novices to compassion training (N = 14); in the second group, ten of these participated again, in addition to three new participants (N = 13). The overall group contained 15 females and 2 males, aged between 37 and 71. The MBCL program was qualitatively evaluated using post-intervention focus group interviews in both groups. In addition, self-report questionnaires assessing depressive symptoms, worry and both self-compassion and mindfulness skills were administered before and after MBCL. No patients dropped out of the intervention. Average attendance was 7.52 (SD 0.73) out of eight sessions. Helpful elements were theory on the emotion regulation systems, practicing self-compassion explicitly and embodiment of a compassionate attitude by the teachers. Unhelpful elements were the lack of a clear structure, lack of time to practice compassion for self and the occurrence of the so-called back draft effect. We adapted the program in accordance with the feedback of the participants. Preliminary results showed a reduction in depressive symptoms in the second group, but not in the first group, and an increase in self-compassion in both groups. Worry and overall mindfulness did not change. MBCL appears to be feasible and acceptable for patients suffering from recurrent depressive symptoms who previously participated in MBCT. Selection bias may have been a factor as only experienced and motivated participants were used; this, however, suited our intention to co-create MBCL in close collaboration with knowledgeable users. Examination of the effectiveness of MBCL in a sufficiently powered randomised controlled trial is needed.

A Mindfulness-Based Compassionate Living Training in a Heterogeneous Sample of Psychiatric Outpatients: a Feasibility Study.

We developed a novel compassion-focused training (mindfulness-based compassionate living; MBCL) and examined its effects in a heterogeneous psychiatric outpatient population with regard to feasibility and changes in levels of depression, anxiety, mindfulness and compassion. The training consisted of nine weekly 2.5-h sessions. Thirty-three patients, who had followed a mindfulness-based stress reduction (MBSR) program or a mindfulness-based cognitive therapy (MBCT) program beforehand, participated in the study (mean age 48.1 years; 82 % female). Participants completed self-report questionnaires before and directly after the MBCL training. Levels of depression, but not of anxiety, reduced, and levels of mindfulness and self-compassion increased. Serious limitations of this study are the small sample size, the lack of a control group and the fact that about half of the participants did not complete the posttraining questionnaires. However, we determined that it is feasible to conduct further research on this novel MBCL training program as a basis for more robust empirical investigation in the future, more specifically examining the effects of MBCL and preferably also the underlying working mechanisms.

Working on self-compassion online: A proof of concept and feasibility study.

OBJECTIVES: Low self-compassion has repeatedly been associated with psychopathology. There are many promising face-to-face group format interventions focusing on self-compassion. We investigated the feasibility of an online self-compassion program. DESIGN: A feasibility and proof-of-concept study of an online adapted Mindfulness-based Compassionate Living (MBCL) program. PARTICIPANTS: Self-referred participants suffering from harsh self-criticism (N = 39) were offered an online program and were asked to complete outcome measures at baseline, after 8 weeks (post-intervention) and after 14 weeks (follow-up). INTERVENTION: The online program consisted of seven sessions, including a first session introducing mindfulness and mindfulness meditation followed by a six-session adaptation of the MBCL program. PRIMARY AND SECONDARY OUTCOME MEASURES: The Self-Compassion Scale (SCS) was the primary outcome measure. Secondary outcome measures were the Forms of Self-criticizing/Attacking and Self-reassuring Scale (FSCRS), the Satisfaction with Life Scale (SWLS), the Comprehensive Inventory of Mindfulness Experience (CHIME), the Fear of Self-compassion (FSC), and the Perceived Stress Questionnaire (PSQ). Additionally, we assessed satisfaction with the program and negative effects related to the program. Furthermore, we used several measures of program usage (number of processed modules, number of logins, time spent in the program, number of diary entries, number of entries in completed exercises). RESULTS: Self-compassion, mindfulness, reassuring-self and satisfaction with life significantly increased whereas inadequate self, hated self, perceived stress and fear of self-compassion significantly decreased from pre- to the 8-week assessment. Results remained stable from post- to the 6-week follow-up. Pre-to-post within-effect sizes were medium to large (ds = 0.50-1.50) and comparable to those found within a face-to-face group format in a similar sample. Time spent in the program significantly predicted self-compassion at post. CONCLUSIONS: The results of this pilot study are promising. However, they must be seen as preliminary since replication in a randomized controlled trial, with clinical measures/diagnoses and a longer follow-up period, is necessary.

Recurrence and Frequency of Disturbance have Cumulative Effect on Methanotrophic Activity, Abundance, and Community Structure.

Alternate prolonged drought and heavy rainfall is predicted to intensify with global warming. Desiccation-rewetting events alter the soil quality and nutrient concentrations which drive microbial-mediated processes, including methane oxidation, a key biogeochemical process catalyzed by methanotrophic bacteria. Although aerobic methanotrophs showed remarkable resilience to a suite of physical disturbances induced as a single event, their resilience to recurring disturbances is less known. Here, using a rice field soil in a microcosm study, we determined whether recurrence and frequency of desiccation-rewetting impose an accumulating effect on the methanotrophic activity. The response of key aerobic methanotroph subgroups (type Ia, Ib, and II) were monitored using qPCR assays, and was supported by a t-RFLP analysis. The methanotrophic activity was resilient to recurring desiccation-rewetting, but increasing the frequency of the disturbance by twofold significantly decreased methane uptake rate. Both the qPCR and t-RFLP analyses were congruent, showing the dominance of type Ia/Ib methanotrophs prior to disturbance, and after disturbance, the recovering community was predominantly comprised of type Ia (Methylobacter) methanotrophs. Both type Ib and type II (Methylosinus/Methylocystis) methanotrophs were adversely affected by the disturbance, but type II methanotrophs showed recovery over time, indicating relatively higher resilience to the disturbance. This revealed distinct, yet unrecognized traits among the methanotroph community members. Our results show that recurring desiccation-rewetting before a recovery in community abundance had an accumulated effect, compromising methanotrophic activity. While methanotrophs may recover well following sporadic disturbances, their resilience may reach a 'tipping point' where activity no longer recovered if disturbance persists and increase in frequency.

Mindfulness training in a heterogeneous psychiatric sample: outcome evaluation and comparison of different diagnostic groups.

OBJECTIVES: To examine outcome after mindfulness training in a heterogeneous psychiatric outpatient population and to compare outcome in different diagnostic groups. METHOD: One hundred and forty-three patients in 5 diagnostic categories completed questionnaires about psychological symptoms, quality of life, and mindfulness skills prior to and immediately after treatment. RESULTS: The mixed patient group as a whole improved significantly on all outcome measures. Differential improvement was found for different diagnostic categories with respect to psychological symptoms and quality of life: Bipolar patients did not improve significantly on these measures. This finding could be explained by longer illness duration and lower baseline severity in the bipolar category. CONCLUSION: Mindfulness training is associated with overall improvement in a heterogeneous outpatient population. Differences in outcome between diagnostic categories may be ascribed to differences in illness duration and baseline severity.

The Dutch complementary and alternative medicine (CAM) protocol: to ensure the safe and effective use of complementary and alternative medicine within Dutch mental health care.

BACKGROUND: Complementary and alternative medicine (CAM) is subject to heated debates and prejudices. Studies show that CAM is widely used by psychiatric patients, usually without the guidance of a therapist and without the use of a solid working method, leading to potential health risks. AIM: The purpose of this study is to facilitate the judicious use of CAM alongside conventional psychiatry in an outpatient psychiatric clinic. METHODS: A search was made through scientific and legal articles and discussion in focus groups. RESULTS: In the Centre for Integrative Psychiatry (CIP) of Lentis in The Netherlands, some carefully selected CAM are offered under strict conditions, alongside conventional treatments. Because of the controversy and the potential health risks, Lentis designed a protocol that is presented. CONCLUSIONS: The CIP hopes, by using this protocol, to better serve and respect the individual needs and preferences of the diversity of psychiatric patients in our Dutch multicultural society, and better protect them from harm.